Biology Lab 4 and 5

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Today & Tomorrow

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1 Invitation to Biology

Unit 1 How Cells work

2 Molecules of Life

3 Cell Structure

4 Energy and Metabolism

5 Capturing and Releasing Energy

Unit 2 GenetiCs

6 DNA Structure and Function

7 Gene Expression and Control

8 How Cells Reproduce

9 Patterns of Inheritance

10 Biotechnology

Unit 3 evolUtion and diversity

11 Evidence of Evolution

12 Processes of Evolution

13 Early Life Forms and the Viruses

14 Plants and Fungi

15 Animal Evolution

Unit 4 eColoGy

16 Population Ecology

17 Communities and Ecosystems

18 The Biosphere and Human Effects

Unit 5 How animals work

19 Animal Tissues and Organs

20 How Animals Move

21 Circulation and Respiration

22 Immunity

23 Digestion and Excretion

24 Neural Control and the Senses

25 Endocrine Control

26 Reproduction and Development

Unit 6 How Plants work

27 Plant Form and Function

28 Plant Reproduction and Development

B r

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C o

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1 Invitation to Biology 1.1 the secret life of earth 4

1.2 life is more than the sum of its Parts 4

1.3 How living things are alike 6

Organisms Require Energy and Nutrients 6

Organisms Sense and Respond to Change 6

Organisms Grow and Reproduce 6

1.4 How living things differ 8

What Is a Species? 8

A Rose by Any Other Name 10

1.5 the science of nature 11

Thinking About Thinking 12

How Science Works 12

Examples of Experiments in Biology 13

1.6 the nature of science 16

Bias in Interpreting Experimental Results 16

Sampling Error 17

Scientific Theories 18

The Scope of Science 19

UNIT 1 HOw CELLS wORk

2 Molecules of Life 2.1 Fear of Frying 24

2.2 start with atoms 25

Why Electrons Matter 26

2.3 From atoms to molecules 28

Ionic Bonds 28

Covalent Bonds 28

2.4 Hydrogen Bonds and water 29

Water Is an Excellent Solvent 30

Water Has Cohesion 31

Water Stabilizes Temperature 31

2.5 acids and Bases 32

2.6 organic molecules 33

What Cells Do to Organic Compounds 33

2.7 Carbohydrates 34

2.8 lipids 36

Fats 36

Phospholipids 36

Waxes 37

Steroids 37

2.9 Proteins 38

The Importance of Protein Structure 39

2.10 nucleic acids 41

3 Cell Structure 3.1 Food for thought 46

3.2 what, exactly, is a Cell? 46

The Cell Theory 46

Components of All Cells 47

Constraints on Cell Size 47

How Do We See Cells? 48

3.3 Cell membrane structure 50

Membrane Proteins 51

3.4 introducing Prokaryotic Cells 52

Biofilms 53

3.5 introducing eukaryotic Cells 54

The Nucleus 54

The Endomembrane System 54

Mitochondria 55

Chloroplasts 56

The Cytoskeleton 56

Extracellular Matrix 58

Cell Junctions 58

3.6 the nature of life 59

C C

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4 Energy and Metabolism 4.1 a toast to alcohol dehydrogenase 64

4.2 life runs on energy 65

4.3 energy in the molecules of life 66

Why Earth Does Not Go Up in Flames 67

Energy In, Energy Out 68

4.4 How enzymes work 68

The Need for Speed 68

Factors That Influence Enzyme Activity 69

Cofactors 70

Metabolic Pathways 71

Controlling Metabolism 71

Electron Transfers 72

4.5 diffusion and membranes 73

Semipermeable Membranes 73

4.6 membrane transport mechanisms 75

Passive Transport 75

Active Transport 76

Membrane Trafficking 76

5 Capturing and Releasing Energy

5.1 a Burning Concern 82

5.2 to Catch a rainbow 83

Storing Energy in Sugars 84

5.3 light-dependent reactions 85

5.4 light-independent reactions 87

Alternative Carbon-Fixing Pathways 87

5.5 a Global Connection 89

Aerobic Respiration in Mitochondria 89

5.6 Fermentation 92

5.7 Food as a source of energy 94

Complex Carbohydrates 94

Fats 94

Proteins 95

UNIT 2 GENETICS

6 DNA Structure and Function 6.1 Cloning 100

6.2 Fame, Glory, and dna structure 102

Discovery of DNA’s Function 102

Discovery of DNA’s Structure 104

DNA Sequence 105

6.3 dna in Chromosomes 106

6.4 dna replication and repair 108

How Mutations Arise 108

7 Gene Expression and Control 7.1 ricin, riP 114

7.2 Gene expression 115

7.3 transcription: dna to rna 116

RNA Modifications 117

7.4 the Genetic Code 118

7.5 translation: rna to Protein 119

7.6 Products of mutated Genes 122

7.7 Control of Gene expression 124

Master Genes 124

Sex Chromosome Genes 125

Lactose Tolerance 125

DNA Methylation 126

CONTENTS v

8 How Cells Reproduce 8.1 Henrietta’s immortal Cells 132

8.2 multiplication by division 133

Cytoplasmic Division 136

8.3 mitosis and Cancer 137

Cell Division Gone Wrong 137

Cancer 138

Telomeres 139

8.4 sex and alleles 140

On the Advantages of Sex 140

8.5 meiosis in sexual reproduction 142

How Meiosis Mixes Alleles 144

From Gametes to Offspring 144

9 Patterns of Inheritance 9.1 menacing mucus 150

9.2 tracking traits 151

Mendel’s Experiments 151

Inheritance in Modern Terms 151

9.3 mendelian inheritance Patterns 152

Monohybrid Crosses 153

Dihybrid Crosses 154

9.4 Beyond simple dominance 155

Incomplete Dominance 155

Codominance 155

Pleiotropy and Epistasis 156

9.5 Complex variation in traits 158

Continuous Variation 159

9.6 Human Genetic analysis 160

Types of Genetic Variation 160

9.7 Human Genetic disorders 161

The Autosomal Dominant Pattern 162

The Autosomal Recessive Pattern 163

The X-Linked Recessive Pattern 164

9.8 Chromosome number Changes 165

Autosomal Change and Down Syndrome 166

Change in the Sex Chromosome Number 166

9.9 Genetic screening 168

10 Biotechnology 10.1 Personal Genetic testing 174

10.2 Finding needles in Haystacks 175

Cutting and Pasting DNA 175

DNA Libraries 176

PCR 177

10.3 studying dna 178

Sequencing the Human Genome 178

Genomics 179

DNA Profiling 179

10.4 Genetic engineering 181

Genetically Modified Microorganisms 181

Designer Plants 181

Biotech Barnyards 182

10.5 modifying Humans 184

Gene Therapy 184

Eugenics 185

UNIT 3 EVOLUTION AND DIVERSITy

11 Evidence of Evolution 11.1 reflections of a distant Past 190

11.2 Confusing discoveries 191

11.3 a Flurry of new ideas 192

Squeezing New Evidence Into Old Beliefs 192

Darwin and the HMS Beagle 193

A Key Insight—Variation in Traits 194

Great Minds Think Alike 195

11.4 Fossil evidence 196

The Fossil Record 196

vi CONTENTS

CONTENTS vii

Radiometric Dating 197

Missing Links 199

11.5 drifting Continents 200

Putting Time Into Perspective 201

11.6 evidence in Form 204

Morphological Divergence 204

Morphological Convergence 205

11.7 evidence in Function 206

Patterns in Animal Development 207

12 Processes of Evolution 12.1 superbug Farms 212

12.2 alleles in Populations 213

An Evolutionary View of Mutations 213

Allele Frequency 214

12.3 modes of natural selection 215

Directional Selection 215

Stabilizing Selection 217

Disruptive Selection 217

12.4 natural selection and diversity 218

Survival of the Sexiest 218

Maintaining Multiple Alleles 219

12.5 Genetic drift and Gene Flow 220

Bottlenecks and the Founder Effect 220

Gene Flow 221

12.6 speciation 222

Reproductive Isolation 222

Allopatric Speciation 224

Sympatric Speciation 224

12.7 macroevolution 226

Evolutionary Theory 228

12.8 Phylogeny 229

Applications of Phylogeny 230

13 Early Life Forms and the Viruses 13.1 the Human micobiome 236

13.2 on the road to life 237

Conditions on the Early Earth 237

Origin of the Building Blocks of Life 237

Origin of Metabolism 238

Origin of Genetic Material 238

Origin of Cell Membranes 239

13.3 origin of the three domains 240

Reign of the Prokaryotes 240

Origin of Eukaryotes 241

13.4 viruses 242

Viral Structure and Replication 242

Bacteriophages 242

Plant Viruses 243

Viruses and Human Health 243

HIV—The AIDS Virus 244

Ebola 245

New Flus 245

13.5 Bacteria and archaea 246

Structure and Function 246

Reproduction and Gene Transfers 246

Metabolic Diversity 247

Domain Archaea 248

Domain Bacteria 248

13.6 Protists 250

Flagellated Protozoans 250

Foraminifera 251

Ciliates 251

Dinoflagellates 252

Apicomplexans 252

Water Molds, Diatoms, and Brown Algae 254

Red Algae 255

Green Algae 255

Amoebas and Slime Molds 256

Choanoflagellates 257

14 Plants and Fungi 14.1 Fungal threats to Crops 262

14.2 Plant traits and evolution 263

Life Cycle 263

Structural Adaptations to Life on Land 264

Reproduction and Dispersal 264

14.3 nonvascular Plants 265

Mosses 265

Liverworts and Hornworts 266

14.4 seedless vascular Plants 266

Ferns 266

Horsetails and Club Mosses 267

14.5 rise of the seed Plants 269

14.6 Gymnosperms 270

Conifers 270

Cycads and Ginkgos 271

Gnetophytes 271

14.7 angiosperms—Flowering Plants 272

Floral Structure and Function 272

A Flowering Plant Life Cycle 273

Keys to Angiosperm Diversity 273

Major Groups 273

Ecology and Human Uses of Angiosperms 274

14.8 Fungal traits and diversity 274

Yeasts, Molds, Mildews, and Mushrooms 274

Lineages and Life Cycles 275

14.9 ecological roles of Fungi 277

Decomposers 277

Parasites 277

Fungal Partnerships 278

Human Uses of Fungi 279

15 Animal Evolution 15.1 medicines From the sea 284

15.2 origins and diversification 285

Animal Origins 285

Evidence of Early Animals 285

Major Groups and Evolutionary Trends 286

15.3 invertebrate diversity 288

Sponges 288

Cnidarians 288

Flatworms 289

Annelids 290

Mollusks 290

Roundworms 291

Arthropods 292

Echinoderms 296

15.4 introducing the Chordates 297

Chordate Traits 297

Invertebrate Chordates 297

Vertebrate Traits and Trends 298

15.5 Fishes and amphibians 299

Jawless Fishes 299

Jawed Fishes 299

Early Tetrapods 300

Modern Amphibians 301

15.6 escape From water—amniotes 302

Amniote Innovations 302

Nonbird Reptiles 302

Birds 303

Mammals 303

15.7 Human evolution 305

Primate Traits 305

Primate Origins and Diversification 305

Australopiths 306

Early Humans 307

Homo Sapiens 308

Neanderthals and Denisovans 308

UNIT 4 ECOLOGy

16 Population Ecology 16.1 a Honkin’ mess 314

16.2 Characteristics of Populations 315

Demographic Traits 315

Collecting Demographic Data 316

16.3 Population Growth 317

Exponential Growth 317

Carrying Capacity and Logistic Growth 318

Density-Independent Factors 319

16.4 life History Patterns 320

Biotic Potential 320

Describing Life Histories 320

Evolution of Life Histories 321

Predation and Life History Evolution 322

viii CONTENTS

CONTENTS ix

16.5 Human Populations 323

Population Size and Growth Rate 323

Fertility Rates and Future Growth 324

Effects of Industrial Development 325

17 Communities and Ecosystems 17.1 Fighting Foreign Fire ants 330

17.2 Community structure 331

Nonbiological Factors 331

Biological Factors 331

17.3 direct species interactions 332

Commensalism and Mutualism 332

Interspecific Competition 333

Predator–Prey Interactions 334

Plants and Herbivores 335

Parasites and Parasitoids 335

17.4 How Communities Change 337

Ecological Succession 337

Adapted to Disturbance 338

Species Losses or Additions 338

17.5 the nature of ecosystems 339

Overview of the Participants 339

Food Chains and Webs 339

Primary Production and Inefficient Energy Transfers 341

17.6 Biogeochemical Cycles 342

The Water Cycle 342

The Phosphorus Cycle 342

The Nitrogen Cycle 344

The Carbon Cycle 345

The Greenhouse Effect and Global Climate Change 346

18 The Biosphere and Human Effects 18.1 Going with the Flow 352

18.2 Factors that affect Climate 353

Air Circulation Patterns 353

Ocean Circulation 354

18.3 the major Biomes 355

Forest Biomes 355

Grasslands and Chaparral 356

Deserts 356

Tundra 356

18.4 aquatic ecosystems 358

Freshwater Ecosystems 358

Marine Ecosystems 358

18.5 Human impact on the Biosphere 360

Increased Species Extinctions 360

Deforestation and Desertification 362

Acid Rain 362

Biological Accumulation and Magnification 363

The Trouble With Trash 363

Destruction of the Ozone Layer 364

Global Climate Change 364

18.6 maintaining Biodiversity 366

The Value of Biodiversity 366

Conservation Biology 366

Ecological Restoration 367

Reducing Human Impacts 368

UNIT 5 HOw ANIMALS wORk

19 Animal Tissues and Organs 19.1 Growing replacement Parts 374

19.2 animal structure and Function 375

Organization and Integration 375

Evolution of Structure and Function 376

19.3 types of animal tissues 376

Epithelial Tissues 376

Connective Tissues 378

Muscle Tissues 379

Nervous Tissue 380

19.4 organs and organ systems 380

Organ Systems 382

19.5 regulating Body temperature 384

20 How Animals Move 20.1 Bulking Up muscles 390

20.2 skeletal systems 391

Types of Skeletons 391

The Human Skeleton 392

Bone Structure and Function 392

Where Bones Meet—Skeletal Joints 393

20.3 Functions of skeletal muscles 395

20.4 How muscle Contracts 396

Muscle Components 396

Sliding Filaments 397

20.5 Fueling muscle Contraction 398

20.6 exercise and inactivity 398

21 Circulation and Respiration 21.1 a shocking save 404

21.2 How substances are moved through a Body 405

Open and Closed Circulatory Systems 405

Evolution of Vertebrate Cardiovascular Systems 406

21.3 Human Cardiovascular system 407

21.4 the Human Heart 408

The Cardiac Cycle 409

Setting the Pace of Contractions 409

21.5 Blood and Blood vessels 410

Components and Functions of Blood 410

High-Pressure Flow in Arteries 410

Adjusting Resistance at Arterioles 411

Capillary Exchange and Function of the Lymph Vessels 411

Back to the Heart 412

21.6 Blood and Cardiovascular disorders 412

Blood Disorders 412

Cardiovascular Disorders 413

21.7 animal respiration 414

Two Sites of Gas Exchange 414

Respiratory Systems 414

21.8 Human respiratory Function 416

From Airways to Alveoli 416

How You Breathe 417

Exchanges at Alveoli 418

Transport of Gases 418

Respiratory Disorders 418

22 Immunity 22.1 Frankie’s last wish 424

22.2 responding to threats 425

The Defenders 426

22.3 innate immunity mechanisms 427

Normal Flora 427

Surface Barriers 427

Complement 428

Phagocytosis 428

Inflammation and Fever 429

Examples of Innate Responses 430

22.4 antigen receptors 431

Antigen Processing 432

22.5 adaptive immune responses 434

Example of an Antibody-Mediated Response 434

Example of a Cell-Mediated Response 436

22.6 immunity Gone wrong 438

Overly Vigorous Responses 438

Immune Deficiency and AIDS 439

22.7 vaccines 441

23 Digestion and Excretion 23.1 Causes and effects of obesity 446

23.2 two types of digestive systems 446

23.3 digestive structure and Function 448

In the Mouth 448

Swallowing 448

The Stomach 449

Digestion in the Small Intestine 450

Absorption in the Small Intestine 451

Concentrating and Eliminating Wastes 452

23.4 Human nutrition 453

Carbohydrates 453

Fats 454

Proteins 454

Vitamins and Minerals 454

USDA Dietary Recommendations 455

23.5 Fluid regulation 456

Fluid Homeostasis 456

Fluid Regulation in Invertebrates 456

Vertebrate Urinary System 457

x CONTENTS

CONTENTS xi

23.6 kidney Function 458

How Urine Forms 458

Feedback Control of Urine Formation 459

Impaired Kidney Function 460

24 Neural Control and the Senses 24.1 impacts of Concussions 466

24.2 animal nervous systems 467

Invertebrate Nervous Systems 467

Vertebrate Nervous Systems 467

24.3 neuron Function 468

Three Types of Neurons 468

Neuroglia—Neuron Helpers 469

Resting Potential 469

The Action Potential 470

The Chemical Synapse 471

Disrupted Synaptic Function 472

Psychoactive Drugs 472

24.4 the Central nervous system 474

Regions of the Human Brain 474

A Closer Look at the Cerebral Cortex 476

The Limbic System—Emotion and Memory 476

The Spinal Cord 477

24.5 the Peripheral nervous system 478

24.6 the senses 480

Sensory Reception and Diversity 480

Sensation to Perception 480

The Chemical Senses—Smell and Taste 481

Detecting Light 482

The Human Eye 482

At the Retina 484

Hearing 484

Sense of Balance 486

The Somatosensory Cortex 487

25 Endocrine Control 25.1 endocrine disrupters 492

25.2 Hormone Function 493

Types of Hormones 494

Hormone Receptors 494

25.3 the Hypothalamus and Pituitary 496

Posterior Pituitary Function 496

Anterior Pituitary Function 496

Growth Disorders 496

25.4 thyroid and Parathyroid Glands 498

Thyroid Hormone 498

Regulation of Calcium 499

25.5 the Pancreas 500

Controlling Blood Glucose 500

Diabetes Mellitus 501

25.6 the adrenal Glands 502

25.7 Hormones and reproductive Function 504

Gonads 504

The Pineal Gland 504

26 Reproduction and Development 26.1 assisted reproduction 510

26.2 modes of reproduction 511

Asexual Reproduction 511

Sexual Reproduction 511

Variations on Sexual Reproduction 511

26.3 stages of animal development 512

26.4 Human reproductive Function 514

Female Reproductive Anatomy 514

Egg Production and Release 515

The Menstrual Cycle 516

Male Reproductive Anatomy 517

How Sperm Form 518

Sexual Intercourse 518

A Sperm’s Journey 519

26.5 reproductive Health 520

Contraception 520

Infertility 521

Sexually Transmitted Diseases 522

26.6 Human development 523

Fertilization 523

From Cleavage to Implantation 524

Embryonic and Fetal Development 525

Functions of the Placenta 528

Maternal Effects on Prenatal Development 528

26.7 Birth and milk Production 529

Childbirth 529

Nourishing the Newborn 529

UNIT 6 HOw PLANTS wORk

27 Plant Form and Function 27.1 leafy Cleanup Crews 534

27.2 tissues in a Plant Body 535

Eudicots and Monocots 537

27.3 stems, leaves, and roots 538

Stems 538

Leaves 540

Roots 542

27.4 Fluid movement in Plants 544

Water Moves Through Xylem 544

Sugars Flow Through Phloem 545

27.5 Plant Growth 546

28 Plant Reproduction and Development

28.1 Plight of the Honeybee 554

28.2 sexual reproduction 555

A New Generation Begins 558

28.3 seeds and Fruits 560

28.4 early development 562

28.5 asexual reproduction 564

Agricultural Applications 564

28.6 Plant Hormones 565

Auxin 566

Cytokinin 567

Gibberellin 568

Abscisic Acid 568

Ethylene 568

28.7 Growth responses 570

Tropisms 570

Photoperiodic Responses 572

appendix i answers to self-Quizzes

appendix ii Periodic table of the elements

appendix iii a Plain english map of the Human Chromosomes

appendix iv Units of measure

xii CONTENTS

P r

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Biology is a huge field, with a wealth of new discover- ies being made every day, and biology-related issues such as climate change, stem cell research, and per- sonal genetics often making headlines. This avalanche of information can be intimidating to non-scientists. This book was designed and written specifically for students who most likely will not become biologists and may never again take another science course. It is an accessible and engaging introduction to biology that provides future decision-makers with an under- standing of basic biology and the process of science.

a wealth of applications This book is packed with everyday applications of biological processes. At every opportunity, we enliven discussions of biologi- cal processes with references to their effects on human health and the environment. This edition also con- tinues to focus on real world applications pertaining to the field of biology, including social issues arising from new research and developments. Descriptions of current research, along with photos of scientists who carry it out, underscore the concept that biology is an ongoing endeavor carried out by a diverse commu- nity of people. Discussions include not only what was discovered, but also how the discoveries were made, how our understanding has changed over time, and what remains to be discovered. These discussions are provided in the context of an accessible introduction to well-established concepts that underpin modern biology. Every topic is examined from an evolutionary perspective, emphasizing the connections between all forms of life.

accessible text Understanding stems from mak- ing connections between concepts and details, so a text with too little detail reads as a series of facts that beg to be memorized. However, excessive detail can overwhelm the introductory student. Thus, we con- stantly strive to strike the perfect balance between level of detail and accessibility. We once again revised the text to eliminate details that do not contribute to a basic understanding of essential concepts. We also know that English is a second language for many introductory students, so we avoid idioms and aim for a clear, straightforward style.

Analogies to familiar objects and phenomena will help students understand abstract concepts. For exam- ple, in the discussion of transpiration in Chapter 27 (Plant Form and Function), we explain that a column of water is drawn upward through xylem as a drinker draws fluid up through a straw.

in-text learning tools To emphasize connections between biological topics, each chapter begins with an application section that explores a current event or controversy directly related to the chapter’s content. For example, a discussion of binge drinking on col- lege campuses introduces the concept of metabolism in Chapter 4. This section presents an overview of the metabolic pathway that breaks down alcohol, linking the function of enzymes in the pathway to hangovers, alcoholism, and cirrhosis. The section is illustrated with a photo of a tailgate party that preceded a recent Notre Dame–Alabama football game, and also a photo of Gary Reinbach just before he died at age 22 of alcoholic liver disease. (In the index, you’ll find health-related applications denoted by red squares and environmental applications by green squares.)

To strengthen a student’s analytical skills and offer insight into contemporary research, each chapter includes an exercise called digging into data that is placed in a section with relevant content. The exer- cise consists of a short text passage—usually about a published scientific experiment—and a table, chart, or other graphic that presents experimental data. A student can use information in the text and graphic to answer a series of questions. For example, the exercise in Chapter 2 asks students to interpret results of a study that examined the effect of dietary fat intake on “good” and “bad” cholesterol levels.

The chapter itself consists of several numbered sections that contain a manageable chunk of informa- tion. Every section ends with a boxed take-home message in which we pose a question that reflects the critical content of the section, and then answer the question in bulleted list format. Every chapter has at least one figure it out question with an answer immediately following. These questions allow students to quickly check their understanding as they read. Mastering scientific vocabulary challenges many stu- dents, so we have included an on-page glossary of key terms introduced in each two-page spread, in addition to a complete glossary at the book’s end. The end-of-chapter material features a visual summary that reinforces each chapter’s key concepts. A self- quiz poses multiple choice and other short answer questions for self-assessment (answers are in Appen- dix I). A set of more challenging critical thinking questions provides thought-provoking exercises for the motivated student. The end matter of several chapters now includes a visual question that rein- forces learning in a nonverbal style.

xiv PREFACE

design and Content revisions Throughout the book, text and art have been revised to help students grasp difficult concepts. The following list highlights some of the revisions to each chapter.

Introduction 1 Invitation to Biology Renewed and updated emphasis on the rel-

evance of new species discovery and the process of science.

Unit 1 How Cells work 2 Molecules of Life New graphic illustrates radioactive decay. 3 Cell Structure Application section updated with current statistics

and ‘pink slime’ story. Micrograph comparisons now feature Para- mecia and include a confocal image. Essay about the nature of life expanded to add Gerald Joyce’s “life is squishy” concept.

4 Energy and Metabolism Application section now illustrated with a real-life example. Diffusion illustrated with a tea bag in hot water.

5 Capturing and Releasing Energy Application section updated with current statistics and illustrated with a current photo of air pollu- tion in China. Yogurt production added to fermentation section.

Unit 2 Genetics 6 DNA Structure and Function Content reorganized: material on clon-

ing folded into Application section for concept connection, and chromosome structure now appears after DNA structure. New art demonstrates how replication errors become mutations.

7 Gene Expression and Control Ricin discussion revised to include medical applications. New material includes hairlessness mutation (in cats), evolution of lactose tolerance, heritability of DNA meth- ylations, telomeres.

8 How Cells Reproduce New material on telomeres, asexual vs. sexual mud snails. New micrograph shows multiple crossovers.

9 Patterns of Inheritance Epistasis is now illustrated with human skin color. New material about environmentally-triggered hemoglobin production in Daphnia; continuous variation in dog face length arising from short tandem repeats foreshadows DNA fingerprint- ing in chapter 10.

10 Biotechnology Updated coverage of personal genetic testing includes social impact of Angelina Jolie’s response to her test. New photos illustrate genetically modified animals. New “who’s the daddy” critical thinking question offers students an opportu- nity to analyze a paternity test based on SNPs.

Unit 3 Evolution and Diversity 11 Evidence of Evolution Photos of 19th century naturalists added

to emphasize the process of science that led to natural selection theory. How banded iron formations provide evidence of the evo- lution of photosynthesis added to fossil section. Plate tectonics art updated to reflect new evidence of lava lamp mantle movements.

12 Processes of Evolution New opening essay on resistance to anti- biotics as an outcome of agricultural overuse (warfarin material now exemplifies directional selection). New art illustrates founder effect, and hypothetical example in text replaced with reduced

diversity of ABO alleles in Native Americans. New art illustrates stasis in coelacanths.

13 Early Life Forms and the Viruses New introductory essay about study of the human microbiome, new coverage of Ebola, and new figure depicting mechanisms of gene exchange in prokaryotes.

14 Plants and Fungi Additional coverage of fungal ecology, including information about white-nose syndrome in bats.

15 Animal Evolution New introductory essay about invertebrates as a source of medicines. Updated information about Neanderthals and added coverage of the newly discovered Dennisovans.

Unit 4 Ecology 16 Population Ecology Updated coverage of human demographics. 17 Communities and Ecosystems New photos illustrate species interac-

tions; updated coverage of the increases in greenhouse gases. 18 The Biosphere and Human Effects New essay about dispersion of the

radioactive material released at Fukushima and new Digging Into Data about bioaccumulation of this material in tuna.

Unit 5 How Animals work 19 Animal Tissues and Organs Updated information about stem cell

research and tissue regeneration in animals. Improved figures depict epithelial and connective tissues.

20 How Animals Move New information about how different muscle fiber types relate to animal locomotion.

21 Circulation and Respiration Improved coverage of insect respiration, including a new photo.

22 Immunity New photos show skin as a surface barrier, a cytotoxic T cell killing a cancer cell, and victims of HIV. Immune response and lymphatic system illustrations updated.

23 Digestion and Excretion Revised essay about obesity and new com- parative information about the ruminant digestive system.

24 Neural Control and the Senses New opening essay about the effects of concussions. Discussion of the human nervous system has been reorganized. New information about echolocation.

25 Endocrine Control Opening essay now focuses on phthalates as endocrine disruptors. New Digging Into Data about BPA’s effect on insulin secretion.

26 Reproduction and Development Updated coverage of assisted repro- ductive technologies. Discussion of human reproductive structure and function has been reorganized.

Unit 6 How Plants work 27 Plant Form and Function Reorganization consolidates growth into a

separate section. Many new photos illustrate stem, leaf, and root structure(s). Material on fire scars added to dendroclimatology.

28 Plant Reproduction and Development Updates reflect current research on colony collapse and ongoing major breakthroughs in the field of plant hormone function. New photos illustrate fruit classification, asexual reproduction, early growth, ABA inhibition of seed germination, and tropisms.

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We owe a special debt to the members of our advisory board, listed below. They helped us shape the book’s design and to choose appro priate content. We appreciate their guidance.

Andrew Baldwin, Mesa Community College Charlotte Borgeson, University of Nevada, Reno Gregory A. Dahlem, Northern Kentucky University Gregory Forbes, Grand Rapids Community College Hinrich Kaiser, Victor Valley Community College Lyn Koller, Pierce College Terry Richardson, University of North Alabama

We also wish to thank the reviewers listed below.

Idris Abdi, Lane College Meghan Andrikanich, Lorain County Community College Lena Ballard, Rock Valley College Barbara D. Boss, Keiser University, Sarasota Susan L. Bower, Pasadena City College James R. Bray Jr., Blackburn College Mimi Bres, Prince George’s Community College Randy Brewton, University of Tennessee Evelyn K. Bruce, University of North Alabama Steven G. Brumbaugh, Green River Community College Chantae M. Calhoun, Lawson State Community College Thomas F. Chubb, Villanova University Julie A. Clements, Keiser University, Melbourne Francisco Delgado, Pima Community College Elizabeth A. Desy, Southwest Minnesota State University Brian Dingmann, University of Minnesota, Crookston Josh Dobkins, Keiser University, online Hartmut Doebel, The George Washington University Pamela K. Elf, University of Minnesota, Crookston Johnny El-Rady, University of South Florida Patrick James Enderle, East Carolina University Jean Engohang-Ndong, BYU Hawaii Ted W. Fleming, Bradley University Edison R. Fowlks, Hampton University Martin Jose Garcia Ramos, Los Angeles City College J. Phil Gibson, University of Oklahoma Judith A. Guinan, Radford University Carla Guthridge, Cameron University Laura A. Houston, Northeast Lakeview–Alamo College Robert H. Inan, Inver Hills Community College Dianne Jennings, Virginia Commonwealth University Ross S. Johnson, Chicago State University Susannah B. Johnson Fulton, Shasta College Paul Kaseloo, Virginia State University Ronald R. Keiper, Valencia Community College West Dawn G. Keller, Hawkeye Community College Ruhul H. Kuddus, Utah Valley State College Dr. Kim Lackey, University of Alabama Vic Landrum, Washburn University Lisa Maranto, Prince George’s Community College Catarina Mata, Borough of Manhattan Community College Kevin C. McGarry, Keiser University, Melbourne Timothy Metz, Campbell University Ann J. Murkowski, North Seattle Community College Alexander E. Olvido, John Tyler Community College Joshua M. Parke, Community College of Southern Nevada Elena Pravosudova, Sierra College Nathan S. Reyna, Howard Payne University Carol Rhodes, Cañada College Todd A. Rimkus, Marymount University Laura H. Ritt, Burlington County College Lynette Rushton, South Puget Sound Community College Erik P. Scully, Towson University

Marilyn Shopper, Johnson County Community College Jennifer J. Skillen, Community College of Southern Nevada Jim Stegge, Rochester Community and Technical College Lisa M. Strain, Northeast Lakeview College Jo Ann Wilson, Florida Gulf Coast University

We were also fortunate to have conversations with the following workshop attendees. The insights they shared proved invaluable.

Robert Bailey, Central Michigan University Brian J. Baumgartner, Trinity Valley Community College Michael Bell, Richland College Lois Borek, Georgia State University Heidi Borgeas, University of Tampa Charlotte Borgenson, University of Nevada Denise Chung, Long Island University Sehoya Cotner, University of Minnesota Heather Collins, Greenville Technical College Joe Conner, Pasadena Community College Gregory A. Dahlem, Northern Kentucky University Juville Dario-Becker, Central Virginia Community College Jean DeSaix, University of North Carolina Carolyn Dodson, Chattanooga State Technical Community College Kathleen Duncan, Foothill College, California Dave Eakin, Eastern Kentucky University Lee Edwards, Greenville Technical College Linda Fergusson-Kolmes, Portland Community College Kathy Ferrell, Greenville Technical College April Ann Fong, Portland Community College Kendra Hill, South Dakota State University Adam W. Hrincevich, Louisiana State University David Huffman, Texas State University, San Marcos Peter Ingmire, San Francisco State Ross S. Johnson, Chicago State University Rose Jones, NW-Shoals Community College Thomas Justice, McLennan Community College Jerome Krueger, South Dakota State University Dean Kruse, Portland Community College Dale Lambert, Tarrant County College Debabrata Majumdar, Norfolk State University Vicki Martin, Appalachian State University Mary Mayhew, Gainesville State College Roy Mason, Mt. San Jacinto College Alexie McNerthney, Portland Community College Brenda Moore, Truman State University Alex Olvido, John Tyler Community College Molly Perry, Keiser University Michael Plotkin, Mt. San Jacinto College Amanda Poffinbarger, Eastern Illinois University Johanna Porter-Kelley, Winston-Salem State University Sarah Pugh, Shelton State Community College Larry A. Reichard, Metropolitan Community College Darryl Ritter, Okaloosa-Walton College Sharon Rogers, University of Las Vegas Lori Rose, Sam Houston State University Matthew Rowe, Sam Houston State University Cara Shillington, Eastern Michigan University Denise Signorelli, Community College of Southern Nevada Jennifer Skillen, Community College of Southern Nevada Jim Stegge, Rochester Community and Technical College Andrew Swanson, Manatee Community College Megan Thomas, University of Las Vegas Kip Thompson, Ozarks Technical Community College Steve White, Ozarks Technical Community College Virginia White, Riverside Community College Lawrence Williams, University of Houston Michael L. Womack, Macon State College

Today & Tomorrow

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acknowledgments

Writing, revising, and illustrating a biology text- book is a major undertaking for two full-time au- thors, but our efforts constitute only a small part of what is required to produce and distribute this one. We are truly fortunate to be part of a huge team of very talented people who are as commit- ted as we are to creating and disseminating an exceptional science education product.

Biology is not dogma; paradigm shifts are a common outcome of the fantastic amount of research in the field. Ideas about what material should be taught and how best to present that material to students changes from one year to the next. It is only with the ongoing input of our many academic reviewers and advisors (previous page) that we can continue to tailor this book to the needs of instructors and students while inte- grating new information and models. We con- tinue to learn from and be inspired by these dedicated educators.

On the production side of our team, the indis- pensable Grace Davidson orchestrated a continu- ous flow of files, photos, and illustrations while managing schedules, budgets, and whatever else happened to be on fire at the time. Grace, thank you as always for your patience and dedication. Thank you also to Cheryl DuBois, John Saranta- kis, and Christine Myaskovsky for your help with photoresearch. Copyeditor Anita Hueftle and proofreader Diane Miller, your valuable sugges- tions kept our text clear and concise.

Yolanda Cossio, thank you for continuing to support us and for encouraging our efforts to innovate and improve. Thanks also to Cengage Production Manager Hal Humphrey, Marketing Manager Tom Ziolkowski, and to Lauren Oliveira, who creates our exciting technology package, Associate Content Developers Casey Lozier and Kellie Petruzzelli, and Product Assistant Victor Luu.

Lisa Starr and Christine Evers, November 2014

Cengage learning testing Powered by Cognero is a flexible, online system that allows you to: • author, edit, and manage test bank content from

multiple Cengage Learning solutions • create multiple test versions in an instant • deliver tests from your LMS, your classroom, or

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instructor Companion site Everything you need for your course in one place! This collection of book- specific lecture and class tools is available online via www.cengage.com/login. Access and download Power- Point presentations, images, instructor’s manual, videos, and more.

Cooperative learning Cooperative Learning: Making Connections in General Biology, 2nd Edi- tion, authored by Mimi Bres and Arnold Weisshaar, is a collection of separate, ready-to-use, short coop- erative activities that have broad application for first year biology courses. They fit perfectly with any style of instruction, whether in large lecture halls or flipped classrooms. The activities are designed to address a range of learning objectives such as reinforcing basic concepts, making connections between various chapters and top- ics, data analysis and graphing, developing problem solving skills, and mastering terminology. Since each activity is designed to stand alone, this collection can be used in a variety of courses and with any text.

mindtap A personalized, fully online digital learn- ing platform of authoritative content, assignments, and services that engages students with interactivity while also offering instructors their choice in the configuration of coursework and enhancement of the curriculum via web-apps known as MindApps. MindApps range from ReadSpeaker (which reads the text out loud to students) to Kaltura (which allows you to insert inline video and audio into your curriculum). MindTap is well beyond an eBook, a homework solution or digital supplement, a resource center website, a course delivery platform, or a Learning Management System. It is the first in a new category—the Personal Learning Experience.

New for this edition! MindTap has an integrated Study Guide, expanded quizzing and application activi- ties, and an integrated Test Bank.

aplia for Biology The Aplia system helps students learn key concepts via Aplia’s focused assignments and active learning opportunities that include randomized, automatically graded questions, exceptional text/art inte- gration, and immediate feedback. Aplia has a full course management system that can be used independently or in conjunction with other course management systems such as MindTap, D2L, or Blackboard.

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1.1 The Secret Life of Earth 4

1.2 Life Is More Than the Sum of Its Parts 4

1.3 How Living Things Are Alike 6

1.4 How Living Things Differ 8

1.5 The Science of Nature 11

1.6 The Nature of Science 16

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1.1 The Secret Life of Earth In this era of detailed satellite imagery and cell phone global positioning systems, could there possibly be any places left on Earth that humans have not yet explored? Actually, there are plenty of them. In 2005, for example, helicopters dropped a team of scientists into the middle of a vast and otherwise inaccessible cloud forest atop New Guinea’s Foja Mountains. Within a few minutes, the explorers realized that their landing site, a dripping, moss-covered swamp, had been untouched by humans. Team member Bruce Beehler remarked, “Everywhere we looked, we saw amazing things we had never seen before. I was shouting. This trip was a once-in-a- lifetime series of shouting experiences.”

How did the explorers know they had landed in uncharted territory? For one thing, the forest was filled with plants and animals previously unknown even to native peoples that have long inhabited other parts of the region. During the next month, the team members discovered many new species, including a rhododendron plant with flowers the size of a plate and a frog the size of a pea. They also came across hundreds of species that are on the brink of extinction in other parts of the world, and some that supposedly had been extinct for decades. The animals had never learned to be afraid of humans, so they could easily be approached. A few were discovered as they casually wandered through campsites (Figure 1.1A).

New species are discovered all the time, often in places much more mundane than Indonesian cloud forests (Figure 1.1B). How do we know what species a par- ticular organism belongs to? What is a species, anyway, and why should discovering a new one matter to anyone other than a scientist? You will find the answers to such questions in this book. They are part of the scientific study of life, biology, which is one of many ways we humans try to make sense of the world around us.

Trying to understand the immense scope of life on Earth gives us some per- spective on where we fit into it. For example, hundreds of new species are discov- ered every year, but about 20 species become extinct every minute in rain forests alone—and those are only the ones we know about. The current rate of extinctions is about 1,000 times faster than normal, and human activities are responsible for the acceleration. At this rate, we will never know about most of the species that are alive on Earth today. Does that matter? Biologists think so. Whether or not we are aware of it, humans are intimately connected with the world around us. Our activities are profoundly changing the entire fabric of life on Earth. These changes are, in turn, affecting us in ways we are only beginning to understand.

Ironically, the more we learn about the natural world, the more we realize we have yet to learn. But don’t take our word for it. Find out what biologists know, and what they do not, and you will have a solid foundation upon which to base your own opinions about how humans fit into this world. By reading this book, you are choos- ing to learn about the human connection—your connection—with all life on Earth.

1.2 Life Is More Than the Sum of Its Parts What, exactly, is the property we call “life”? We may never actually come up with a good definition, because living things are too diverse, and they consist of the same basic components as nonliving things. When we try to define life, we end up with a long list of properties that differentiate living from nonliving things. These

Figure 1.1 Newly discovered species. Each of the thousands of species discovered every year is a reminder that we do not yet know all of the organ- isms living on our own planet. We don’t even know how many to look for. Information about the 1.8 million species we do know about is being collected in The Encyclopedia of Life, an online database maintained by collaborative effort (www.eol.org). (A) Tim Laman/National Geographic Stock; (B) Courtesy East Carolina University.

Application

A. Paul oliver discovered this tree frog perched on a sack of rice during a rainy campsite lunch in New Guinea’s Foja Mountains. The explorers dubbed the new species “Pinocchio frog” after the Disney character because the male frog’s long nose inflates and points upward during times of excitement.

B. Dr. Jason Bond holds a new species of trapdoor spider he discovered in sand dunes of california beaches in 2008. Bond named the spider Aptostichus stephencol- berti, after TV personality Stephen colbert.

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properties often emerge from the interactions of basic components. To understand how that works, take a look at these groups of squares:

A property called “roundness” emerges when the squares are organized one way, but not other ways. The idea that different structures can be assembled from the same basic building blocks is a recurring theme in our world, and also in biology.

Life has successive levels of organization, with new properties emerging at each level (Figure 1.2). This organization begins with interactions between atoms, which are fundamental units of matter—the building blocks of all substances

. Atoms bond together to form molecules

. There are no atoms unique to living things, but there are unique molecules. In today’s natural world, only living things make the “molecules of life,” which are lipids, proteins, DNA, RNA, and complex carbohydrates. The emergent property of “life” appears at the next level, when many molecules of life become organized as a cell

. A cell is the smallest unit of life. Cells survive and reproduce themselves using energy, raw materials, and information in their DNA.

Some cells live and reproduce independently; others do so as part of a mul- ticelled organism

. An organism is an individual that consists of one or more cells. In most multicelled organisms, cells are organized as tissues, organs, and organ systems that interact to keep the body working properly.

A population is a group of interbreeding individuals of the same type, or spe- cies, living in a given area

. At the next level, a community consists of all popula- tions living in a given area

. Communities may be large or small, depending on the area defined.

The next level of organization is the ecosystem, which is a community inter- acting with its physical and chemical environment

. The most inclusive level, the biosphere, encompasses all regions of Earth’s crust, waters, and atmosphere in which organisms live

Figure 1.2 Levels of organization in nature.

Atoms are fundamental units of matter.

Molecules consist of atoms.

cells consist of molecules.

organisms consist of cells.

Populations consist of organisms.

communities consist of populations.

Ecosystems consist of communities interacting with their environment.

The biosphere consists of all ecosystems on Earth.

Take-Home Message 1.2 how do living things differ from nonliving things?

• All things, living or not, consist of the same building blocks: atoms. Atoms bond together to form molecules.

• In today’s natural world, only living things make lipids, proteins, DNA, rNA, and com- plex carbohydrates. The unique properties of life emerge as these molecules become organized into cells.

• Higher levels of life’s organization include multicelled organisms, populations, com- munities, ecosystems, and the biosphere.

atom Fundamental building block of all matter.

biology The scientific study of life.

biosphere All regions of Earth where organisms live.

cell Smallest unit of life.

community All populations of all species in a given area.

ecosystem A community interacting with its environment.

molecule Two or more atoms bonded together.

organism Individual that consists of one or more cells.

population Group of interbreeding individuals of the same species that live in a given area.

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1.3 How Living Things Are Alike Even though we cannot precisely define “life,” we can intuitively understand what it means because all living things share a particular set of key features. All require ongoing inputs of energy and raw materials; all sense and respond to change; and all pass DNA to offspring.

Organisms Require Energy and Nutrients Not all living things eat, but all require energy and nutrients on an ongoing basis. Inputs of both are essential to maintain the functioning of individual organisms and the organization of life in general. A nutrient is a substance that an organism needs for growth and survival but cannot make for itself.

Organisms spend a lot of time acquiring energy and nutrients (Figure 1.3). However, the source of energy and the type of nutrients acquired differ among organisms. These differences allow us to classify living things into two catego- ries: producers and consumers. A producer makes its own food using energy and simple raw materials it obtains from nonbiological sources. Plants are producers; by a process called photosynthesis, they use the energy of sunlight to make sugars from water and carbon dioxide (a gas in air). Consumers, by contrast, cannot make their own food. A consumer obtains energy and nutrients by feeding on other organisms. Animals are consumers. So are decomposers, which feed on the wastes or remains of other organisms. The leftovers from consumers’ meals end up in the environment, where they serve as nutrients for producers. Said another way, nutri- ents cycle between producers and consumers.

Unlike nutrients, energy is not cycled. It flows through the world of life in one direction: from the environment, through organisms, and back to the environ- ment. This flow maintains the organization of every living cell and body, and it also influences how individuals interact with one another and their environment. The energy flow is one-way, because with each transfer, some energy escapes as heat, and cells cannot use heat as an energy source. Thus, energy that enters the world of life eventually leaves it (we return to this topic in Chapter 5).

Organisms Sense and Respond to Change An organism cannot survive for very long in a changing environment unless it adapts to the changes. Thus, every living thing has the ability to sense and respond to change both inside and outside of itself (Figure 1.4). Consider how, after you eat, the sugars from your meal enter your bloodstream. The added sugars set in motion a series of events that causes cells throughout the body to take up sugar faster, so the sugar level in your blood quickly falls. This response keeps your blood sugar level within a certain range, which in turn helps keep your cells alive and your body functioning properly.

All of the fluids outside of cells make up a body’s internal environment. That environment must be kept within certain ranges of temperature and other con- ditions, or the cells that make up the body will die. By sensing and adjusting to change, organisms keep conditions in the internal environment within a range that favors survival. Homeostasis is the name for this process, and it is one of the defin- ing features of life.

Organisms Grow and Reproduce With little variation, the same types of mol- ecules perform the same basic functions in every organism. For example, informa- tion in an organism’s DNA (deoxyribonucleic acid) guides ongoing functions that sustain the individual through its lifetime. Such functions include development:

Figure 1.3 the one-way flow of energy and the cycling of materials in the world of life. Top, © Victoria Pinder, www.flickr.com/photos/vixstarplus.

P R O D U C E R S plants and other self-feeding organisms

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C O N S U M E R S animals, most fungi, many protists, bacteria

Producers harvest energy from the environment. Some of that energy flows from producers to consumers.

Nutrients that get incorporated into the cells

of producers and consumers are eventually released back into the environment (by decomposi-

tion, for example). Producers then take up some of the

released nutrients.

All energy that enters the world of life eventually flows out of it, mainly as heat released back to the environment.

consumer acquiring energy and nutrients by eating a producer

producer acquiring energy and nutrients from its environment

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DNA

Figure 1.4 Organisms sense and respond to stimulation. This baby orangutan is laughing in response to being tickled. Apes and humans make different sounds when being tickled, but the airflow patterns are so similar that we can say apes really do laugh. © Dr. Marina Davila Ross, University of Portsmouth.

consumer organism that gets energy and nutrients by feeding on the tissues, wastes, or remains of other organisms.

development Multistep process by which the first cell of a new multicelled organism gives rise to an adult.

DNA Deoxyribonucleic acid; carries hereditary infor- mation that guides development and other activities.

growth In multicelled species, an increase in the number, size, and volume of cells.

homeostasis Process in which an organism keeps its internal conditions within tolerable ranges by sensing and responding to change.

inheritance Transmission of DNA to offspring.

nutrient Substance that an organism needs for growth and survival but cannot make for itself.

photosynthesis Process by which a producer uses light energy to make sugars from carbon dioxide and water.

producer organism that makes its own food using energy and nonbiological raw materials from the environment.

reproduction Process by which parents produce offspring.

the process by which the first cell of a new individual becomes a multicelled adult; growth: increases in cell number, size, and volume; and reproduction: processes by which individuals produce offspring.

Individuals of every natural population are alike in certain aspects of their body form and behavior because their DNA is very similar: Orangutans look like orangutans and not like caterpillars because they inherited orangutan DNA, which differs from caterpillar DNA in the information it carries. Inheritance refers to the transmission of DNA to offspring. All organisms receive their DNA from one or more parents.

DNA is the basis of similarities in form and function among organisms. How- ever, the details of DNA molecules differ, and herein lies the source of life’s diversity. Small variations in the details of DNA’s structure give rise to differences among indi- viduals, and also among types of organisms. As you will see in later chapters, these differences are the raw material of evolutionary processes.

Take-Home Message 1.3 how are all living things alike?

• A one-way flow of energy and a cycling of nutrients sustain life’s organization. • organisms sense and respond to conditions inside and outside themselves. They

make adjustments that keep conditions in their internal environment within a range that favors cell survival, a process called homeostasis.

• All organisms use information in the DNA they inherited from their parent or parents to develop, grow, and reproduce. DNA is the basis of similarities and differences in form and function among organisms.

Figure 1.5 A few representative prokaryotes. (A) top left, Dr. Richard Frankel; top right, Science Source; bottom left, www.zahnarzt-stuttgart .com; bottom right, © Susan Barnes; (B) left, Dr. Terry Beveridge, Visuals Unlimited/Corbis; right, © Dr. Harald Huber, Dr. Michael Hohn, Prof. Dr. K.O. Stetter, University of Regensburg, Germany.

A. Bacteria are the most numerous organisms on Earth. clockwise from upper left, a bacterium with a row of iron crystals that acts like a tiny compass; a common resident of cat and dog stomachs; spiral cyanobacteria; types found in dental plaque.

B. Archaea may resemble bacteria, but they are more closely related to eukaryotes. These are two types of archaea from a hydrothermal vent on the seafloor.

1.4 How Living Things Differ Living things differ tremendously in their observable characteristics. Various clas- sification schemes help us organize what we understand about the scope of this variation, which we call Earth’s biodiversity.

For example, organisms can be grouped on the basis of whether they have a nucleus, which is a saclike structure containing a cell’s DNA. Bacteria (singular, bacterium) and archaea (singular, archaeon) are organisms whose DNA is not contained within a nucleus. All bacteria and archaea are single-celled, which means each organism consists of one cell (Figure 1.5). Collectively, these organisms are the most diverse representatives of life. Different kinds are producers or consumers in nearly all regions of Earth. Some inhabit such extreme environments as frozen des- ert rocks, boiling sulfurous lakes, and nuclear reactor waste. The first cells on Earth may have faced similarly hostile conditions.

Traditionally, organisms without a nucleus have been called prokaryotes, but the designation is now used only informally. This is because, despite the similar appearance of bacteria and archaea, the two types of cells are less related to one another than we once thought. Archaea turned out to be more closely related to eukaryotes, which are organisms whose DNA is contained within a nucleus. Some eukaryotes live as individual cells; others are multicelled (Figure 1.6). Eukaryotic cells are typically larger and more complex than bacteria or archaea.

Protists are the simplest eukaryotes, but as a group they vary dramatically, from single-celled consumers to giant, multicelled producers.

Fungi (singular, fungus) are eukaryotic consumers that secrete substances to break down food externally, then absorb nutrients released by this process. Many fungi are decomposers. Most fungi, including those that form mushrooms, are mul- ticellular. Fungi that live as single cells are called yeasts.

Plants are multicelled eukaryotes, and the vast majority of them are photosyn- thetic producers that live on land. Besides feeding themselves, plants also serve as food for most other land-based organisms.

Animals are multicelled eukaryotic consumers that ingest tissues or juices of other organisms. Unlike fungi, animals break down food inside their body. They also develop through a series of stages that lead to the adult form. All animals actively move about during at least part of their lives.

What Is a Species? Each time we discover a new species, or unique kind of organism, we name it. Taxonomy, the practice of naming and classifying spe- cies, began thousands of years ago, but naming species in a consistent way did not become a priority until the eighteenth century. At the time, European explor- ers who were just discovering the scope of life’s diversity started having more and more trouble communicating with one another because species often had multiple names. For example, the dog rose (a plant native to Europe, Africa, and Asia) was alternately known as briar rose, witch’s briar, herb patience, sweet briar, wild briar, dog briar, dog berry, briar hip, eglantine gall, hep tree, hip fruit, hip rose, hip tree, hop fruit, and hogseed—and those are only the English names! Species often had multiple scientific names too, in Latin that was descriptive but often cumbersome. The scientific name of the dog rose was Rosa sylvestris inodora seu canina (odorless woodland dog rose), and also Rosa sylvestris alba cum rubore, folio glabro (pinkish white woodland rose with smooth leaves).

An eighteenth-century naturalist, Carolus Linnaeus, standardized a two-part naming system that we still use. By the Linnaean system, every species is given a

animal Multicelled consumer that develops through a series of stages and moves about during part or all of its life.

archaea Group of single-celled organisms that lack a nucleus but are more closely related to eukaryotes than to bacteria.

bacteria The most diverse and well-known group of single-celled organisms that lack a nucleus.

biodiversity Scope of variation among living organisms.

eukaryote organism whose cells characteristically have a nucleus.

fungus Single-celled or multicelled eukaryotic con- sumer that breaks down material outside itself, then absorbs nutrients released from the breakdown.

plant A multicelled, typically photosynthetic producer.

prokaryote Single-celled organism with no nucleus.

protists A group of diverse, simple eukaryotes.

species unique type of organism.

taxonomy Practice of naming and classifying species.

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Animals are multicelled con- sumers that ingest tissues or juices of other organisms. All actively move about during at least part of their life.

Fungi are eukaryotic consumers that secrete substances to break down food outside their body. Most are multicelled (left), but some are single-celled (above).

plants are multicelled eukaryotes. Almost all plants are photosynthetic producers, and most of them have roots, stems, and leaves.

protists are a group of extremely diverse eukary- otes that range from giant multicelled seaweeds to microscopic single cells.

Figure 1.6 A few representative eukaryotes. Protists: from left, © worldswildlifewonders/Shutterstock.com; top middle, Courtesy of Allen W. H. Bé and David A. Caron; bottom middle, © Emiliania Huxleyi photograph, Vita Pariente, scanning electron micrograph taken on a Jeol T330A instrument at Texas A&M University Electron Microscopy Center; top right, M I Walker/Science Source; middle right, © Carolina Biological Supply Company; bottom right, Oliver Meckes/Science Source; Plants: left, © Jag.ca.Shutterstock.com; right, © Martin Ruegner/Radius Images/Getty Images; Fungi, left, Edward S. Ross; right, London Scientific Films/Oxford Scientific/Getty Images; Animals: left, Shironina/Shutterstock.com; middle, © Martin Zimmerman, Science, 1961, 133:73–79, © AAAS; right, © Pixtal/SuperStock.

unique two-part scientific name. The first part of a scientific name is the genus (plural, genera), a group of species that share a unique set of features. The second part is the specific epithet. Together, the genus name and the specific epithet desig- nate one species. Thus, the dog rose now has one official name, Rosa canina, that is recognized worldwide.

Genus and species names are always italicized. For example, Panthera is a genus of big cats. Lions belong to the species Panthera leo. Tigers belong to a different species in the same genus (Panthera tigris), and so do leopards (P. pardus). Note how the genus name may be abbreviated after it has been spelled out once.

A Rose by Any Other Name The individuals of a species share a unique set of inherited traits. For example, giraffes normally have very long necks, brown spots on white coats, and so on. These are morphological (structural) traits. Individuals of a species also share biochemical traits (they make and use the same molecules) and behavioral traits (they respond the same way to certain stimuli, as when hungry giraffes feed on tree leaves). We can rank species into ever more inclusive catego- ries based on some subset of traits it shares with other species. Each rank, or taxon (plural, taxa), is a group of organisms that share a unique set of traits. Each category above species—genus, family, order, class, phylum (plural, phyla), kingdom, and domain—consists of a group of the next lower taxon (Figure 1.7). Using this system, we can sort all life into a few categories (Figure 1.8).

It is easy to tell that orangutans and caterpillars are different species because they appear very different. Distinguishing between species that are more closely related may be much more challenging (Figure 1.9). In addition, traits shared by members of a species often vary a bit among individuals, as eye color does among

Figure 1.7 taxonomic classification of five species that are related at different levels. Each species has been assigned to ever more inclusive groups, or taxa: in this case, from genus to domain. From the left, Joaquim Gaspar; © kymkemp.com; Sylvie Bouchard/Shutterstock.com; Courtesy of Melissa S. Green, www.flickr.com/photos/henkimaa; © Grodana Sarkotic.

Answer: Marijuana, apple, prickly rose, and dog roseFigure It Out: Which of the plants shown here are in the same order?

domain kingdom phylum

class order

family genus

species

A “species” is a convenient but artificial construct of the human mind.

genus A group of species that share a unique set of traits.

taxon Group of organisms that share a unique set of traits.

Eukarya Plantae Magnoliophyta Magnoliopsida Apiales Apiaceae Daucus carota

wild carrot Eukarya Plantae Magnoliophyta Magnoliopsida rosales rosaceae Malus domestica

apple Eukarya Plantae Magnoliophyta Magnoliopsida rosales rosaceae Rosa acicularis

prickly rose Eukarya Plantae Magnoliophyta Magnoliopsida rosales rosaceae Rosa canina

dog rose Eukarya Plantae Magnoliophyta Magnoliopsida rosales cannabaceae Cannabis sativa

marijuana

INVITATIoN To BIoLoGy ChApter 1 11

Bacteria Archaea Eukarya

B. Three-domain classification system. The Eukarya domain includes protists, plants, fungi, and animals.

Figure 1.9 Four butterflies, two species: Which are which? The top row shows two forms of the species Heliconius melpomene; the bottom row, two forms of H. erato.

H. melpomene and H. erato never cross-breed. Their alternate but similar patterns of coloration evolved as a shared warning signal to predatory birds that these but- terflies taste terrible. © 2006 Axel Meyer, “Repeating Patterns of Mimicry.” PLoS Biology Vol. 4, No. 10, e341 doi:10.1371/journal.pbio.0040341. Used with Permission.

Figure 1.8 two little ways to see the big picture of life. Lines in such diagrams indicate evolutionary connections.

people. How do we decide whether similar-looking organisms belong to the same species? The short answer to that question is that we rely on whatever information we have. Early naturalists studied anatomy and distribution—essentially the only methods available at the time—so species were named and classified according to what they looked like and where they lived. Today’s biologists are able to compare traits that the early naturalists did not even know about, including biochemical ones.

The discovery of new information sometimes changes the way we distinguish a particular species or how we group it with others. For example, Linnaeus grouped plants by the number and arrangement of reproductive parts, a scheme that resulted in odd pairings such as castor-oil plants with pine trees. Having more information today, we place these plants in separate phyla.

Evolutionary biologist Ernst Mayr defined a species as one or more groups of individuals that potentially can interbreed, produce fertile offspring, and do not interbreed with other groups. This “biological species concept” is useful in many cases, but it is not universally applicable. For example, we may never know whether two widely separated populations could interbreed if they got together. As another example, populations often continue to interbreed even as they diverge, so the exact moment at which two populations become two species is often impossible to pinpoint. We return to speciation and how it occurs in Chapter 12, but for now it is important to remember that a “species” is a convenient but artificial construct of the human mind.

1.5 The Science of Nature Most of us assume that we do our own thinking, but do we, really? You might be surprised to find out how often we let others think for us. Consider how a school’s job (which is to impart as much information to students as quickly as possible)

Take-Home Message 1.4 how do organisms differ from one another?

• organisms differ in their details; they show tremendous variation in observable characteristics.

• We divide Earth’s biodiversity into broad groups based on traits such as having a nucleus or being multicellular.

• Each species is given a unique, two-part scientific name. • classification systems group species on the basis of shared traits.

Bacteria Archaea FungiPlants AnimalsProtists

A. Six-kingdom classification system. The protist kingdom includes the most ancient multicelled and all single-celled eukaryotes.

How do my own biases affect what I’m learning?

meshes perfectly with a student’s job (which is to acquire as much knowledge as quickly as possible). In this rapid-fire exchange of information, it can be very easy to forget about the quality of what is being exchanged. Any time you accept informa- tion without questioning it, you let someone else think for you.

Thinking About Thinking Critical thinking is the deliberate process of judg- ing the quality of information before accepting it. “Critical” comes from the Greek kriticos (discerning judgment). When you use critical thinking, you move beyond the content of new information to consider supporting evidence, bias, and alterna- tive interpretations. How does the busy student manage this? Critical thinking does not necessarily require extra time, just a bit of extra awareness. There are many ways to do it. For example, you might ask yourself some of the following questions while you are learning something new:

What message am I being asked to accept? Is the message based on facts or opinion? Is there a different way to interpret the facts? What biases might the presenter have? How do my own biases affect what I’m learning?

Such questions are a way of being conscious about learning. They can help you decide whether to allow new information to guide your beliefs and actions.

How Science Works Critical thinking is a big part of science, the systematic study of the observable world and how it works. A scientific line of inquiry usually begins with curiosity about something observable, such as (for example) a decrease in the number of birds in a particular area. Typically, a scientist will read about what others have discovered before making a hypothesis, a testable explanation for a natural phenomenon. An example of a hypothesis would be, “The number of birds is decreasing because the number of cats is increasing.”

A prediction, or statement of some condition that should exist if the hypoth- esis is correct, comes next. Making predictions is often called the if–then process, in which the “if ” part is the hypothesis, and the “then” part is the prediction: If the number of birds is decreasing because the number of cats is increasing, then reduc- ing the number of cats should stop the decline.

Next, a researcher will test the prediction. Tests may be performed on a model, or analogous system, if working with an object or event directly is not possible. For

A. Studying the ecological benefits of weedy buffer zones on farms.

B. Measuring how much wood is produced by extremely old trees.

control group Group of individuals identical to an experimental group except for the independent vari- able under investigation.

critical thinking Evaluating information before accepting it.

data Experimental results.

experiment A test designed to support or falsify a prediction.

experimental group In an experiment, a group of individuals who have a certain characteristic or receive a certain treatment.

hypothesis Testable explanation of a natural phenomenon.

model Analogous system used for testing hypotheses.

prediction Statement, based on a hypothesis, about a condition that should exist if the hypothesis is correct.

science Systematic study of the observable world.

scientific method Making, testing, and evaluating hypotheses.

variable In an experiment, a characteristic or event that differs among individuals or over time.

INVITATIoN To BIoLoGy ChApter 1 13

example, animal diseases are often used as models of similar human diseases. Care- ful observations are one way to test predictions that flow from a hypothesis. So are experiments: tests designed to support or falsify a prediction. A typical experiment explores a cause-and-effect relationship using variables, which are characteristics or events that can differ among individuals or over time.

Biological systems are typically complex, with many interdependent variables. It can be difficult to study one variable separately from the rest. Thus, biology researchers often test two groups of individuals simultaneously. An experimental group is a set of individuals that have a certain characteristic or receive a certain treatment. An experimental group is tested side by side with a control group, which is identical to the experimental group except for one independent variable: the characteristic or the treatment being tested. Any differences in experimental results between the two groups is likely to be an effect of changing the variable. Test results—data—that are consistent with the prediction are evidence in support of the hypothesis. Data inconsistent with the prediction are evidence that the hypothesis is flawed and should be revised.

A necessary part of science is reporting one’s results and conclusions in a stan- dard way, such as in a peer-reviewed journal article. The communication gives other scientists an opportunity to evaluate the information for themselves, both by check- ing the conclusions drawn and by repeating the experiments. Forming a hypothesis based on observation, and then systematically testing and evaluating the hypothesis, are collectively called the scientific method (Table 1.1).

Examples of Experiments in Biology There are many different ways to do research, particularly in biology (Figure 1.10). Some biologists survey, simply observing without making or testing hypotheses. Others make hypotheses based on observations, and leave the testing to others. However, despite a broad range of approaches, scientific experiments are typically designed in a consistent way, so the effects of changing one variable at a time can be measured. To give you a sense of how biology experiments work, we summarize two published studies here.

In 1996 the U.S. Food and Drug Administration (FDA) approved Olestra®, a fat replacement manufactured from sugar and vegetable oil, as a food additive. Potato chips were the first Olestra-containing food product to be sold in the United States. Controversy about the chip additive soon raged. Many people complained of intes- tinal problems after eating the chips, and thought that the Olestra was at fault. Two

table 1.1 the Scientific Method

observe some aspect of nature.

Think of an explanation for your observation (in other words, form a hypothesis).

Test the hypothesis. a. Make a prediction based on the hypothesis. b. Test the prediction using experiments or

surveys. c. Analyze the results of the tests (data).

Decide whether the results of the tests support your hypothesis or not (form a conclusion).

report your results to the scientific community.

Figure 1.10 A few examples of scientific research in the field of biology. (A) Photo by Scott Bauer, USDA/ARS; (B) MICHAEL NICHOLS/National Geographic Creative; (C) © Roger W. Winstead, NC State University; (D) National Cancer Institute; (E) Courtesy of Susanna López-Legentil.

e. Discovering medically active natural products made by marine animals.

C. Improving efficiency of biofuel production from agricultural waste.

D. Devising a vaccine that helps prevent cancer.

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years later, researchers at the Johns Hopkins University School of Medicine designed an experiment to test whether Olestra causes cramps. The researchers made the fol- lowing prediction: if Olestra causes cramps, then people who eat Olestra should be more likely to get cramps than people who do not eat it. To test the prediction, they used a Chicago theater as a “laboratory.” They asked 1,100 people between the ages of thirteen and thirty-eight to watch a movie and eat their fill of potato chips. Each person received an unmarked bag containing 13 ounces of chips. In this experiment, the individuals who received Olestra-laden potato chips were the experimental group, and the individuals who received regular chips were the control group.

A few days after the movie, the researchers contacted all of the people who participated in the experiment and collected any reports of post-movie gastrointes- tinal problems. Of 563 people making up the experimental group, 89 (15.8 percent) reported having cramps. However, so did 93 of the 529 people (17.6 percent) mak- ing up the control group—who had eaten the regular chips. People were about as likely to get cramps whether or not they ate chips made with Olestra. These results did not support the prediction, so the researchers concluded that eating Olestra does not cause cramps (Figure 1.11).

A different experiment that took place in 2005 investigated whether certain behaviors of peacock butterflies help the insects avoid predation by birds. The researchers performing this experiment began with two observations. First, when a peacock butterfly rests, it folds its wings, so only the dark underside shows (Fig- ure 1.12A). Second, when a butterfly sees a predator approaching, it repeatedly flicks its wings open, while also moving them in a way that produces a hissing sound and a series of clicks (Figure 1.12B).

The researchers were curious about why the peacock butterfly flicks its wings. After they reviewed earlier studies, they came up with two hypotheses that might explain the wing-flicking behavior.

Figure 1.11 the steps in a scientific experiment to determine whether Olestra causes intestinal cramps. A report of this study was published in the Journal of the American Medical Association in January 1998. Left, © Bob Jacobson/Corbis; background right, © SuperStock.

Eats regular potato chips

Eats Olestra potato chips

Olestra® causes intestinal cramps.

People who eat potato chips made with Olestra will be more likely to get intestinal cramps than those who eat potato chips made without Olestra.

89 of 563 people get cramps later (15.8%)

93 of 529 people get cramps later (17.6%)

Percentages are about equal. People who eat potato chips made with Olestra are just as likely to get intestinal cramps as those who eat potato chips made without Olestra. These results do not support the hypothesis.

Control Group Experimental Group

Hypothesis

Prediction

Experiment

Results

Conclusion

INVITATIoN To BIoLoGy ChApter 1 15

1. Wing-flicking probably attracts predatory birds, but it also exposes brilliant spots that resemble owl eyes. Anything that looks like owl eyes is known to startle small, butterfly-eating birds, so exposing the wing spots might scare off predators.

2. The hissing and clicking sounds produced when the peacock butterfly moves its wings may be an additional defense that deters predatory birds.

The researchers then used their hypotheses to make the following predictions:

1. If exposing brilliant wing spots startles butterfly-eating birds, then peacock but- terflies missing their spots will be more likely to get eaten.

2. If hissing and clicking sounds deter birds butterfly-eating birds, then peacock butterflies unable to make these sounds will be more likely to get eaten.

The next step was the experiment. The researchers used a black marker to cover up the wing spots of some butterflies, and scissors to cut off the sound-making part of the wings of others. A third group had both treatments, their wings painted and also cut. The researchers then put each butterfly into a large cage with a hungry blue tit (Figure 1.12C) and watched the pair for thirty minutes.

Figure 1.12D lists the results of the experiment. All butterflies with unmodified wing spots survived, regardless of whether they made sounds. By contrast, only half of the butterflies that had spots painted out but could make sounds survived. Most

B. When a predatory bird approaches, a butterfly flicks its wings open and closed, reveal- ing brilliant spots and producing hissing and clicking sounds.

A. With wings folded, a resting peacock butterfly resembles a dead leaf, so it is appropriately camou- flaged from predatory birds.

C. researchers tested whether the wing-flicking behavior of peacock but- terflies affected predation by blue tits.

D. The researchers painted out the spots of some butterflies, cut the sound-making part of the wings on others, and did both to a third group; then exposed each butterfly to a hungry blue tit for 30 minutes. results are listed on the right.

experimental treatment

Number of Butterflies eaten (of total)

Spots painted out 5 of 10

Wings cut 0 of 8

Spots painted, wings cut 8 of 10

None 0 of 9

Figure 1.12 testing peacock butterfly defenses. (A) © Matt Rowlings, www.eurobutterflies.com; (B) © Adrian Vallin; (C) © Antje Schulte; (D) Proceedings of the Royal Society of London, Series B (2005) 272: 1203–1207.

Answer: 20 percent

Figure It Out: What percentage of butterflies with spots painted and wings cut survived the test?

Digging Into Data peacock Butterfly predator Defenses The photographs below represent the experimental and control groups used in the peacock butterfly experiment. Identify the experimental groups, and match them up with the relevant control group(s). Hint: Identify which variable is being tested in each group (each variable has a control). Adrian Vallin, Sven Jakobsson, Johan Lind and Christer Wiklund, Proc. R. Soc. B (2005: 272, 1203, 1207). Used with permission of The Royal Society and the author.

A. Wing spots painted out

B. Wing spots vis- ible; wings silenced

C. Wing spots painted out; wings silenced

D. Wings painted but spots visible

e. Wings cut but not silenced

F. Wings painted, spots visible; wings cut, not silenced

16 INTroDucTIoN

of the silenced butterflies with painted-out spots were eaten quickly. The test results confirmed both predictions, so they support the hypotheses. Predatory birds are indeed deterred by peacock butterfly wing-flicking behavior.

1.6 The Nature of Science Bias in Interpreting Experimental Results Experimenting with a single vari- able apart from all others is not often possible, particularly when studying humans. For example, remember that the people who participated in the Olestra experiment were chosen randomly, which means the study was not controlled for gender, age, weight, medications taken, and so on. These variables may well have influenced the experiment’s results.

Humans are by nature subjective, and scientists are no exception. Research- ers risk interpreting their results in terms of what they want to find out. That is

Take-Home Message 1.5 how does science work?

• The scientific method consists of making, testing, and evaluating hypotheses. It is one way of critical thinking—systematically judging the quality of information before allowing it to guide one’s beliefs and actions.

• Natural processes are often very complex and influenced by many interacting variables.

• Experiments help researchers unravel causes of complex natural processes by focus- ing on the effects of changing a single variable.

Figure 1.13 example of how generalizing from a subset can lead to a conclusion that is incorrect. (A) Tim Laman/ National Geographic Stock; (B) © Bruce Beehler/ Conservation International.

B. In science, discov- ery of an error is not always bad news. Kris Helgen holds a golden- mantled tree kangaroo he found during the 2005 Foja Mountains survey. This kangaroo species is extremely rare in other areas, so it was thought to be criti- cally endangered prior to the expedition.

A. The cloud forest that covers about 2 million acres of New Guinea’s Foja Mountains is extremely remote and difficult to access, even for natives of the region. The first major survey of this forest occurred in 2005.

The scientific community consists of critically thinking people trying to poke holes in one another’s ideas.

INVITATIoN To BIoLoGy ChApter 1 17

why they typically design experiments that will yield quantitative results, which are counts or some other data that can be measured or gathered objectively. Quantita- tive results minimize the potential for bias, and also give other scientists an oppor- tunity to repeat the experiments and check the conclusions drawn from them. This last point gets us back to the role of critical thinking in science. Scientists expect one another to recognize and put aside bias in order to test hypotheses in ways that may prove them wrong. If a scientist does not, then others will, because exposing errors is just as useful as applauding insights. The scientific community consists of critically thinking people trying to poke holes in one another’s ideas. Ideally, their collective efforts make science a self-correcting endeavor.

Sampling Error Researchers cannot always observe all individuals of a group. For example, the explorers you read about in Section 1.1 did not—and could not— survey every uninhabited part of the Foja Mountains. The cloud forest alone cloaks more than 2 million acres (Figure 1.13A), so surveying all of it would take unrealis- tic amounts of time and effort.

When researchers cannot directly observe all individuals of a population, all instances of an event, or some other aspect of nature, they may test or survey a subset. Results from the subset are then used to make generalizations about the whole. However, generalizing from a subset is risky because subsets are not neces- sarily representative of the whole. Consider the golden-mantled tree kangaroo, an animal first discovered in 1993 on a single forested mountaintop in New Guinea. For more than a decade, the species was never seen outside of that habitat, which is getting smaller every year because of human activities. Thus, the golden-mantled tree kangaroo was considered to be one of the most endangered animals on the planet. Then, in 2005, the New Guinea explorers discovered that this kangaroo spe- cies is fairly common in the Foja Mountain cloud forest (Figure 1.13B). As a result, biologists now believe its future is secure, at least for the moment.

Sampling error is a difference between results obtained from a subset, and results from the whole (Figure 1.14A). Sampling error may be unavoidable, but knowing how it can occur helps researchers design their experiments to minimize it. For example, sampling error can be a substantial problem with a small subset, so experimenters try to start with a relatively large sample, and they repeat their experiments (Figure 1.14B). To understand why these practices reduce the risk of sampling error, think about flipping a coin. There are two possible outcomes of each flip: The coin lands heads up, or it lands tails up. Thus, the chance that the coin will land heads up is one in two (1/2), or 50 percent. However, when you flip a coin repeatedly, it often lands heads up, or tails up, several times in a row. With just 3 flips, the proportion of times that the coin actually lands heads up may not even be close to 50 percent. With 1,000 flips, however, the overall proportion of times the coin lands heads up is much more likely to approach 50 percent.

Probability is the measure, expressed as a percentage, of the chance that a particular outcome will occur. That chance depends on the total number of pos- sible outcomes. For instance, if 10 million people enter a drawing, each has the same probability of winning: 1 in 10 million, or (an extremely improbable) 0.00001 per- cent. Analysis of experimental data often includes probability calculations. If there is a very low probability that a result has occurred by chance alone, the result is said to be statistically significant. In this context, the word “significant” does not refer to the result’s importance. Rather, it means that a rigorous statistical analysis has shown a very low probability (usually 5 percent or less) of the result being incorrect because of sampling error.

A. Natalie chooses a random jelly bean from a jar. She is blindfolded, so she does not know that the jar contains 120 green and 280 black jelly beans.

The jar is hidden from Natalie’s view before she removes her blindfold. She sees one green jelly bean in her hand and assumes that the jar must hold only green jelly beans. This assumption is incorrect: 30 percent of the jelly beans in the jar are green, and 70 percent are black. The small sample size has resulted in sampling error.

B. Still blindfolded, Natalie randomly chooses 50 jelly beans from the jar. She ends up choosing 10 green and 40 black beans.

The larger sample leads Natalie to assume that one- fifth of the jar’s jelly beans are green (20 percent) and four-fifths are black (80 percent). The larger sample more closely approximates the jar’s actual green-to- black ratio of 30 percent to 70 percent.

The more times Natalie repeats the sampling, the greater her chance of guessing the actual ratio.

Figure 1.14 how sample size affects sampling error. © Gary Head.

probability The chance that a particular outcome of an event will occur; depends on the total number of outcomes possible.

sampling error Difference between results derived from testing an entire group of events or individuals, and results derived from testing a subset of the group.

statistically significant refers to a result that is sta- tistically unlikely to have occurred by chance alone.

18 INTroDucTIoN

W in

g �i

ck s

p er

m in

ut e

– spots + sound

– spots – sound

+ spots – sound

Variation in data is often shown as error bars on a graph (Figure 1.15). Depend- ing on the graph, error bars may indicate variation around an average for one sample set, or the difference between two sample sets.

Scientific Theories Suppose a hypothesis stands even after years of tests. It is consistent with all data ever gathered, and it has helped us make successful predic- tions about other phenomena. When a hypothesis meets these criteria, it is consid- ered to be a scientific theory (Table 1.2). To give an example, all observations to date have been consistent with the hypothesis that matter consists of atoms. Scien- tists no longer spend time testing this hypothesis for the compelling reason that, since we started looking 200 years ago, no one has discovered matter that consists of anything else. Thus, scientists use the hypothesis, now called atomic theory, to make other hypotheses about matter.

Scientific theories are our best objective descriptions of the natural world. How- ever, they can never be proven absolutely, because to do so would necessitate testing under every possible circumstance. For example, in order to prove atomic theory, the atomic composition of all matter in the universe would have to be checked—an impossible task even if someone wanted to try.

Like all hypotheses, a scientific theory can be disproven by a single observa- tion or result that is inconsistent with it. For example, if someone discovers a form of matter that does not consist of atoms, atomic theory would have to be revised. The potentially falsifiable nature of scientific theories means that science has a built-in system of checks and balances. A theory is revised until no one can prove it to be incorrect. The theory of evolution, which states that change occurs in a line of descent over time, still holds after a century of observations and testing. As with all other scientific theories, no one can be absolutely sure that it will hold under all possible conditions, but it has a very high probability of not being wrong. Few other theories have withstood as much scrutiny.

You may hear people apply the word “theory” to a speculative idea, as in the phrase “It’s just a theory.” This everyday usage of the word differs from the way it is used in science. Speculation is an opinion, belief, or personal conviction that is not necessarily supported by evidence. A scientific theory is different. By definition, a scientific theory is supported by a large body of evidence, and it is consistent with all known data.

A scientific theory also differs from a law of nature, which describes a phe- nomenon that has been observed to occur in every circumstance without fail, but for which we do not have a complete scientific explanation. The laws of

Science helps us communicate our experiences without bias.

Figure 1.15 example of error bars in a graph. This graph was adapted from the peacock butterfly research described in Section 1.5.

The researchers recorded the number of times each butterfly flicked its wings in response to an attack by a bird.

The squares represent average frequency of wing flicking for each sample set of butterflies. The error bars that extend above and below the dots indicate the range of values—the sampling error.

Answer: 22 times per minute

Figure It Out: What was the fastest rate at which a butterfly with no spots or sound flicked its wings?

INVITATIoN To BIoLoGy ChApter 1 19

thermo dynamics, which describe energy, are examples. We understand how energy behaves, but not exactly why it behaves the way it does.

The Scope of Science Science helps us be objective about our observations in part because of its limitations. For example, science does not address many questions, such as “Why do I exist?” Answers to such questions can only come from within as an integration of the personal experiences and mental connections that shape our consciousness. This is not to say subjective answers have no value, because no human society can function for long unless its individuals share standards for making judgments, even if they are subjective. Moral, aesthetic, and philosophi- cal standards vary from one society to the next, but all help people decide what is important and good. All give meaning to our lives.

Neither does science address the supernatural, or anything that is “beyond nature.” Science neither assumes nor denies that supernatural phenomena occur, but scientists often cause controversy when they discover a natural explanation for something that was thought to have none. Such controversy arises when a society’s moral standards are interwoven with its understanding of nature. Nicolaus Copernicus proposed in 1540 that Earth orbits the sun. Today that idea is generally accepted, but the prevailing belief system had Earth as the immovable center of the universe. In 1610, Galileo Galilei published evidence for the Copernican model of the solar system, an act that resulted in his imprisonment. He was publicly forced to recant his work, spent the rest of his life under house arrest, and was never allowed to publish again.

As Galileo’s story illustrates, exploring a traditional view of the natural world from a scientific perspective is often misinterpreted as a violation of morality. As a group, scientists are no less moral than anyone else, but they follow a particular set of rules that do not necessarily apply to others: Their work concerns only the natu- ral world, and their ideas must be testable by other scientists.

Science helps us communicate our experiences of the natural world without bias. As such, it may be as close as we can get to a universal language. We are fairly sure, for example, that the laws of gravity apply everywhere in the universe. Intelli- gent beings on a distant planet would likely understand the concept of gravity. Thus, we might well use gravity or another scientific concept to communicate with them, or anyone, anywhere. The point of science, however, is not to communicate with aliens. It is to find common ground here on Earth.

Take-Home Message 1.6 Why does science work?

• researchers minimize sampling error by using large sample sizes and by repeating their experiments. Probability calculations can show whether a result is unlikely to have occurred by chance alone.

• Science is concerned only with testable ideas about observable aspects of nature. • Ideally, science is a self-correcting process because it is carried out by a community

of people who systematically check one another’s work and conclusions. • Because a scientific theory is thoroughly tested and revised until no one can prove it

wrong, it is our best way of objectively describing the natural world.

law of nature Generalization that describes a consistent natural phenomenon for which there is incomplete scientific explanation.

scientific theory Hypothesis that has not been disproven after many years of rigorous testing.

theory Main premises

Atomic theory All matter consists of atoms.

Big bang The universe originated with an explosion and continues to expand.

cell theory All organisms consist of one or more cells, the cell is the basic unit of life, and all cells arise from existing cells.

Evolution change occurs in the inher- ited traits of a population over generations.

Global warming Human activities are causing Earth’s average temperature to increase.

Plate tectonics Earth’s crust is cracked into pieces that move in relation to one another.

table 1.2 examples of Scientific theories

Summary Section 1.1 Biology is the scientific study of life. We know about only a fraction of the organisms that live on Earth, in part because we have explored only a fraction of its inhabited regions.

Section 1.2 Biologists think about life at different levels of organization, with new properties emerging at successively higher levels. all matter consists of atoms, which bond together to form molecules. Organisms are individuals that consist of one or more cells, the organizational level at which life emerges. a population is a group of interbreeding individuals of a species in a given area; a community is all populations of all species in a given area. an ecosystem is a community interacting with its environment. the biosphere includes all regions of Earth that hold life.

Section 1.3 life has underlying unity in that all living things have similar characteristics: (1) all organisms require energy and nutrients to sustain themselves. Producers harvest energy from the environment to make their own food by processes such as

photosynthesis; consumers ingest other organisms, or their wastes or remains. (2) organisms keep the conditions in their internal environment within ranges that their cells tolerate—a process called homeostasis. (3) DNA contains information that guides an organism’s growth, development, and reproduction. the passage of Dna from parents to offspring is inheritance.

Section 1.4 the many types of organisms that currently exist on Earth differ greatly in details of body form and function. Biodiversity is the sum of differences among living things. Bacteria and archaea are prokaryotes, single-celled organisms whose Dna

is not contained within a nucleus. the Dna of single-celled or multicelled eukaryotes (protists, plants, fungi, and animals) is contained within a nucleus.

Each species has a two-part name. the first part is the genus name. When combined with the specific epithet, it designates the particular species. With taxonomy, species are ranked into ever more inclusive taxa on the basis of shared traits.

Section 1.5 Critical thinking, the self-directed act of judging the quality of information as one learns, is an important part of science. generally, a researcher observes something in nature, forms a hypothesis (testable explanation) for it, then makes

a prediction about what might occur if the hypothesis is correct. Predictions are tested with observations, experiments, or both.

Experiments typically are performed on an experimental group as compared with a control group, and sometimes on model systems. Conclusions are drawn from data. a hypothesis that is not consistent with data is modified or discarded. the scientific method consists of making, testing, and evaluating hypotheses, and sharing results with the scientific community.

Biological systems are usually influenced by many interacting variables. Research approaches differ, but experiments are designed in a consistent way, in order to study a single cause-and- effect relationship in a complex natural system.

Section 1.6 Small sample size increases the potential for sampling error in experimental results. In such cases, a subset may be tested that is not representative of the whole. Researchers design experiments carefully to minimize sampling error and

bias, and they use probability calculations to check the statistical significance of their results.

Science helps us be objective about our observations because it is concerned only with testable ideas about observable aspects of nature. opinion and belief have value in human culture, but they are not addressed by science. a scientific theory is a long- standing hypothesis that is useful for making predictions about other phenomena. It is our best way of objectively describing nature. a law of nature is a phenomenon that occurs without fail, but has an incomplete scientific explanation.

Answers in Appendix I

1. are fundamental building blocks of all matter. a. Cells c. organisms b. atoms d. Molecules

2. the smallest unit of life is the . a. atom c. cell b. molecule d. organism

3. is the transmission of Dna to offspring. a. Reproduction c. Homeostasis b. Development d. Inheritance

4. a process by which an organism produces offspring is called . a. reproduction c. homeostasis b. development d. inheritance

Self-Quiz

INVITATIoN To BIoLoGy ChApter 1 21

15. In one survey, fifteen randomly selected students were found to be taller than 6 feet. this data led to the conclusion that the average height of a student is greater than 6 feet. this is an example of . a. experimental error c. a subjective opinion b. sampling error d. experimental bias

1. a person is declared to be dead upon the irreversible ceasing of spontaneous body functions: brain activity, or blood circulation and respiration. However, only about 1% of a person’s cells have to die in order for all of these things to happen. How can some- one be dead when 99% of his or her cells are still alive?

2. Explain the difference between a one-celled organism and a single cell of a multicelled organism.

3. Why would you think twice about ordering from a restaurant menu that lists only the second part of the species name (not the genus) of its offerings? Hint: look up Ursus americanus, Ceanothus americanus, Bufo americanus, Homarus america- nus, Lepus americanus, and Nicrophorus americanus.

4. once there was a highly intelligent turkey that had nothing to do but reflect on the world’s regularities. Morning always started out with the sky turning light, followed by the master’s footsteps, which were always followed by the appearance of food. other things varied, but food always followed footsteps. the sequence of events was so predictable that it eventually became the basis of the turkey’s theory about the goodness of the world. one morning, after more than 100 confirmations of this theory, the turkey listened for the master’s footsteps, heard them, and had its head chopped off.

any scientific theory is modified or discarded upon discovery of contradictory evidence. the absence of absolute certainty has led some people to conclude that “theories are irrelevant because they can change.” If that is so, should we stop doing scientific research? Why or why not?

5. In 2005, researcher Woo-suk Hwang reported that he had made immortal stem cells from human patients. His research was hailed as a breakthrough for people affected by degenerative diseases, because stem cells may be used to repair a person’s own damaged tissues. Hwang published his results in a peer- reviewed journal. In 2006, the journal retracted his paper after other scientists discovered that Hwang’s group had faked their data. Does the incident show that results of scientific studies cannot be trusted? or does it confirm the usefulness of a scien- tific approach, because other scientists discovered and exposed the fraud?

5. organisms require and to maintain themselves, grow, and reproduce. a. Dna; energy c. nutrients; energy b. food; sunlight d. Dna; cells

6. move around for at least part of their life.

7. By sensing and responding to change, an organism keeps conditions in its internal environment within ranges that its cells can tolerate. this process is called . a. sampling error c. homeostasis b. development d. critical thinking

8. Dna . a. guides form c. is transmitted from

and function parents to offspring b. is the basis of traits d. all of the above

9. a butterfly is a(n) (choose all that apply). a. organism e. consumer b. domain f. producer c. species g. prokaryote d. eukaryote h. trait

10. a bacterium is (choose all that apply). a. an organism c. an animal b. single-celled d. a eukaryote

11. Bacteria, archaea, and Eukarya are three .

12. a control group is . a. a set of individuals that have a characteristic under study or

receive an experimental treatment b. the standard against which an experimental group is

compared c. the experiment that gives conclusive results

13. Science addresses only that which is . a. alive c. variable b. observable d. indisputable

14. Match the terms with the most suitable description. life a. if–then statement probability b. unique type of organism species c. emerges with cells scientific theory d. testable explanation hypothesis e. measure of chance prediction f. makes its own food producer g. time-tested hypothesis

Critical thinking

2.1 Fear of Frying 24

2.2 Start With Atoms 25

2.3 From Atoms to Molecules 28

2.4 Hydrogen Bonds and Water 29

2.5 Acids and Bases 32

2.6 Organic Molecules 33

2.7 Carbohydrates 34

2.8 Lipids 36

2.9 Proteins 38

2.10 Nucleic Acids 41

M o

le c

u le

s o

f l

if e

24 Unit 1 HOW CeLLS WOrk

2.1 Fear of Frying The human body requires only about a tablespoon of fat each day to stay healthy, but most people in developed countries eat far more than that. The average Ameri- can eats about 70 pounds of fat per year, which may be part of the reason why the average American is overweight. Being overweight increases one’s risk for many chronic illnesses. However, the total quantity of fat in the diet may have less impact on health than the types of fats. Fats are more than inert molecules that accumulate in strategic areas of our bodies. They are the main constituents of cell membranes, and as such they have powerful effects on cell function.

The typical fat molecule has three fatty acid tails, each a long chain of carbon atoms that can vary a bit in structure. Fats with a certain arrangement of hydrogen atoms around those carbon chains are called trans fats. Small amounts of trans fats occur naturally in red meat and dairy products, but the main source of these fats in the American diet is an artificial food product called partially hydrogenated vegetable oil. Hydrogenation is a manufacturing process that adds hydrogen atoms to oils in order to change them into solid fats. In 1908, Procter & Gamble Co. developed partially hydrogenated soybean oil as a substitute for the more expensive solid animal fats they had been using to make candles. By 1911, more households in the United States became wired for electricity, so the demand for candles was waning. P & G needed another way to sell its proprietary fat. Partially hydrogenated vegetable oil looks a lot like lard, so the company began aggressively marketing it as a revolutionary new food: a solid cooking fat with a long shelf life, mild flavor, and lower cost than lard or butter.

By the mid-1950s, hydrogenated vegetable oil had become a major part of the American diet. For decades, it was considered to be healthier than animal fats because it was made from plants, but we now know otherwise. Trans fats, which are abun- dant in hydrogenated vegetable oils, raise the level of cholesterol in our blood more than any other fat, and they directly alter the function of our arter- ies and veins. The effects of such changes are quite serious. Eating as little as 2 grams per day (about 0.4 teaspoon) of hydrogenated vegetable oil measurably increases one’s risk of atherosclerosis (hardening of the arteries), heart attack, and diabetes. A small serv- ing of french fries made with hydrogenated vegetable oil contains about 5 grams of trans fat (Figure 2.1). At this writing, hydrogenated oil is still a component of many manufactured and fast foods: french fries, stick margarines, ready-to-use frostings, cookies, crackers, cakes and pancakes, peanut butter, pies, doughnuts, muffins, chips, microwave popcorn, pizzas, burritos, chicken nuggets, fish sticks, and so on.

All organisms consist of the same kinds of molecules, but small differences in the way those molecules are put together can have big effects. With this concept, we introduce you to the chemistry of life. This is your chemistry. It makes you far more than the sum of your body’s molecules.

Figure 2.1 Unhealthy trans fats are abundant in partially hydrogenated oils commonly used to make manufactured and fast foods. © Kentoh/Shutterstock.com.

Application

MOLeCuLeS OF LiFe Chapter 2 25

2.2 Start With Atoms reMeMBer: Atoms are fundamental units of matter—the building blocks of all substances (Section 1.2).

Even though atoms are about 20 million times smaller than a grain of sand, they consist of even smaller subatomic particles. Positively charged protons (p+) and uncharged neutrons occur in an atom’s core, or nucleus. Negatively charged elec- trons (e–) move around the nucleus (Figure 2.2). Charge is an electrical property: Opposite charges attract, and like charges repel. A typical atom has about the same number of electrons and protons. The negative charge of an electron is the same magnitude as the positive charge of a proton, so the two charges cancel one another. Thus, an atom with the same number of electrons and protons carries no charge.

All atoms have protons. The number of protons in the nucleus is called the atomic number, and it determines the type of atom, or element. Elements are pure substances, each consisting only of atoms with the same number of protons in their nucleus. For example, the element carbon has an atomic number of 6 (Figure 2.3). All atoms with six protons in their nucleus are carbon atoms, no matter how many electrons or neutrons they have. Elemental carbon (the substance) consists only of carbon atoms, and all of those atoms have six protons. Each of the 118 known ele- ments has a symbol that is typically an abbreviation of its Latin or Greek name (see Appendix II). Carbon’s symbol, C, is from carbo, the Latin word for coal. Coal is mostly carbon.

All atoms of an element have the same number of protons, but they can differ in the number of other subatomic particles. Those that differ in the number of neu- trons are called isotopes. The total number of neutrons and protons in the nucleus of an isotope is its mass number. Mass number is written as a superscript to the left of the element’s symbol. For example, the most common isotope of hydrogen has one proton and no neutrons, so it is designated 1H. Other hydrogen isotopes include deuterium (2H, one proton and one neutron) and tritium (3H, one proton and two neutrons).

The most common carbon isotope has six protons and six neutrons (12C). Another naturally occurring carbon isotope, 14C, has six protons and eight neutrons (6 + 8 = 14). Carbon 14 is an example of a radioisotope, or radioactive isotope. Atoms of a radioisotope have an unstable nucleus that breaks up spontaneously. As a nucleus breaks up, it emits radiation (subatomic particles, energy, or both), a process called radioactive decay. The atomic nucleus cannot be altered by ordinary means, so radioactive decay is unaffected by external factors such as temperature, pressure, or whether the atoms are part of molecules.

Each radioisotope decays at a predictable rate into predictable products. For example, when carbon 14 decays, one of its neutrons splits into a proton and an electron. The nucleus emits the electron as radiation. Thus, a carbon atom with eight neutrons and six protons (14C) becomes a nitrogen atom, with seven neutrons and seven protons (14N):

This process is so predictable that we can say with certainty that about half of the atoms in any sample of 14C will be 14N atoms after 5,730 years. The predictability of

atomic number Number of protons in the atomic nucleus; determines the element.

charge electrical property; opposite charges attract, and like charges repel.

electron Negatively charged subatomic particle.

element A pure substance that consists only of atoms with the same number of protons.

isotopes Forms of an element that differ in the num- ber of neutrons their atoms carry.

mass number Of an isotope, the total number of protons and neutrons in the atomic nucleus.

neutron uncharged subatomic particle in the atomic nucleus.

nucleus Core of an atom; occupied by protons and neutrons.

proton Positively charged subatomic particle that occurs in the nucleus of all atoms.

radioactive decay Process by which atoms of a radioisotope emit energy and subatomic particles when their nucleus spontaneously breaks up.

radioisotope isotope with an unstable nucleus.

Figure 2.2 atoms consist of subatomic particles. Models such as this do not show what atoms really look like. electrons move in defined, three-dimensional spaces about 10,000 times bigger than the nucleus. Protons and neutrons occur in the nucleus.

Figure 2.3 example of an element: carbon. Left, Theodore Gray/Visuals Unlimited, Inc.

electron

neutron

proton

an atom

+ +

–

C 6

12mass number

element symbol

atomic number

carbon

elemental substance

element name

nucleus of 14C, with 6 protons, 8 neutrons

nucleus of 14N, with 7 protons, 7 neutrons

nucleus of 14C, with 6 protons, 8 neutrons

nucleus of 14N, with 7 protons, 7 neutrons

26 Unit 1 HOW CeLLS WOrk

Figure 2.5 Shell models. each circle (shell) represents one energy level. To make these models, we fill the shells with electrons from the innermost shell out, until there are as many electrons as the atom has protons. The number of protons in each model is indicated.

radioactive decay makes it possible for scientists to estimate the age of a rock or fos- sil by measuring its isotope content (we return to this topic in Section 11.4).

Radioisotopes are often used in tracers, which are substances with a detect- able component. For example, a molecule in which an atom (such as 12C) has been replaced with a radioisotope (such as 14C) can be used as a radioactive tracer. When delivered into a biological system, a radioactive tracer may be followed as it moves through the system with instruments that detect radiation (Figure 2.4).

Why Electrons Matter The more we learn about electrons, the weirder they seem. Consider that an electron has mass but no size, and its position in space is described as more of a smudge than a point. It carries energy, but only in incremen- tal amounts (this concept will be important to remember when you learn how cells harvest and release energy). An electron gains energy only by absorbing the precise amount needed to boost it to the next energy level. Likewise, it loses energy only by emitting the exact difference between two energy levels.

Imagine that an atom is a multilevel apartment building with a nucleus in the basement. Each “floor” of the building corresponds to a certain energy level, and each has a certain number of “rooms” available for rent. Two electrons can occupy each room. Pairs of electrons populate rooms from the ground floor up. The farther an electron is from the nucleus in the basement, the greater its energy. An elec- tron can move to a room on a higher floor if an energy input gives it a boost, but it immediately emits the extra energy and moves back down.

brain

lungs

heart

liver

kidneys

Nonsmoker Smoker

Figure 2.4 pet scans. PeT scans use radioactive tracers to form a digital image of a process in the body’s interior. These two PeT scans reveal the activity of a molecule called MAO-B in the body of a nonsmoker (left) and a smoker (right). The activ- ity is color-coded from red (highest activity) to purple (lowest). Low MAO-B activity is associated with violence, impulsiveness, and other behavioral problems. Brookhaven National Laboratory.

a. the first shell corresponds to the first energy level, and it can hold up to 2 electrons. Hydrogen has one proton, so it has 1 electron and one vacancy. A helium atom has 2 protons, 2 electrons, and no vacancies.

B. the second shell corresponds to the second energy level, and it can hold up to 8 electrons. Carbon has 6 electrons, so its first shell is full. its second shell has 4 electrons and four vacancies. Oxygen has 8 electrons and two vacancies. Neon has 10 electrons and no vacancies.

C. the third shell corresponds to the third energy level, and it can hold up to 8 electrons. A sodium atom has 11 electrons, so its first two shells are full; the third shell has one electron. Thus, sodium has seven vacancies. Chlorine has 17 electrons and one vacancy. Argon has 18 electrons and no vacancies.

answer: Hydrogen, carbon, oxygen, sodium, and chlorineFigure it Out: Which of these models have unpaired electrons in their outer shell?

carbon (C)second shell oxygen (O) neon (Ne)

6 8 10

sodium (Na)third shell chlorine (Cl) argon (Ar)

181711

one electron

one proton

hydrogen (H)first shell

helium (He)

carbon (C)second shell oxygen (O) neon (Ne)

6 8 10

sodium (Na)third shell chlorine (Cl) argon (Ar)

181711

one electron

one proton

hydrogen (H)first shell

helium (He)

carbon (C)second shell oxygen (O) neon (Ne)

6 8 10

sodium (Na)third shell chlorine (Cl) argon (Ar)

181711

one electron

one proton

hydrogen (H)first shell

helium (He)

MOLeCuLeS OF LiFe Chapter 2 27

A shell model helps us visualize how electrons populate atoms (Figure 2.5). In this model, nested “shells” correspond to successively higher energy levels. Thus, each shell includes all of the rooms on one floor (energy level) of our atomic apart- ment building. We draw a shell model of an atom by filling it with electrons from the innermost shell out, until there are as many electrons as the atom has protons. There is only one room on the first floor, and it fills up first. In hydrogen, the sim- plest atom, a single electron occupies that room (Figure 2.5A). Helium, with two protons, has two electrons that fill the room —and the first shell. In larger atoms, more electrons rent the second-floor rooms (Figure 2.5B). When the second floor fills, more electrons rent third-floor rooms (Figure 2.5C), and so on.

When an atom’s outermost shell is filled with electrons, we say that it has no vacancies, and it is in its most stable state. Helium, neon, and argon are examples

of elements with no vacancies. Atoms of these elements are chemically stable, which means they have very little tendency to interact with other atoms. Thus, these elements occur most frequently in nature as solitary atoms. By contrast, when an atom’s outermost shell has room for another electron, it has a vacancy. Atoms with vacancies tend to get rid of them by interacting with other atoms; in other words, they are chemi- cally active. For example, the sodium atom (Na) in Figure 2.5C has one electron in its outer (third) shell, which can hold eight. With seven vacancies, we can predict that this atom is chemically active. In fact, this particular sodium atom is not just active, it is extremely so. Why? The shell model shows that a sodium atom has an unpaired electron, but in the real world, electrons really like to be in pairs when they populate atoms. Atoms that have

unpaired electrons are called free radicals. With a few exceptions, free radicals are very unstable, easily forcing electrons upon other atoms or ripping electrons away from them. This property makes free radicals dangerous to life. A sodium atom with 11 electrons (a sodium radical) quickly evicts the one unpaired electron, so that its second shell—which is full of electrons—becomes its outermost, and no vacancies remain. This is the atom’s most stable state. The vast majority of sodium atoms on Earth are like this one, with 11 protons and 10 electrons.

Atoms with an unequal number of protons and electrons are ions. An ion car- ries a net (or overall) charge. Sodium ions (Na+) offer an example of how atoms gain a positive charge by losing an electron (Figure 2.6A). Other atoms gain a negative charge by accepting an electron (Figure 2.6B).

free radical Atom with an unpaired electron.

ion Atom or molecule that carries a net charge.

shell model Model of electron distribution in an atom.

tracer A substance that can be traced via its detect- able component.

Figure 2.6 ion formation.

vacancy

no vacancy

ic ha

el S

. Y am

as hi

ta / C

or bi

answer: No

Figure it Out: Does a chloride ion have an unpaired electron?

11p+

11e–

charge: 0

Sodium atom

Chlorine atom

charge: 0

17p+

17e–

Chloride ion

charge: –1

17p+

18e–

11p+

10e–

charge: +1

Sodium ion

electron loss

1111

1717

electron gain

a. A sodium atom (Na) becomes a positively charged sodium ion (Na+) when it loses the single electron in its third shell. The atom’s full second shell is now its outer- most, so it has no vacancies.

B. A chlorine atom (Cl) becomes a negatively charged chloride ion (Cl–) when it gains an electron and fills the vacancy in its third, outermost shell.

11p+

11e–

charge: 0

Sodium atom

Chlorine atom

charge: 0

17p+

17e–

Chloride ion

charge: –1

17p+

18e–

11p+

10e–

charge: +1

Sodium ion

electron loss

1111

1717

electron gain

Take-Home Message 2.2 What are atoms?

• Atoms consist of electrons moving around a nucleus of protons and neutrons. The number of protons determines the element. isotopes are forms of an element that have different numbers of neutrons.

• unstable nuclei of radioisotopes emit radiation as they spontaneously break down (decay). radioisotopes decay at a predictable rate to form predictable products.

• An atom’s electrons are the basis of its chemical behavior. When an atom’s outermost shell is not full of electrons, it has a vacancy and it is chemically active. Atoms that get rid of vacancies by gaining or losing electrons become ions (charged).

28 Unit 1 HOW CeLLS WOrk

2.3 From Atoms to Molecules reMeMBer: The same building blocks, arranged different ways, form different products; atoms bond together to form molecules (Section 1.2).

A chemical bond is an attractive force that arises between two atoms, and it is one way that atoms rid themselves of vacancies. Chemical bonds make molecules out of atoms. A molecule consists of atoms held together in a particular number and arrangement by chemical bonds. For example, a water molecule consists of three atoms: two hydrogen atoms bonded to the same oxygen atom (Figure 2.7). Because a water molecule has atoms of two or more elements, it is called a compound. Other molecules, including molecular oxygen (a gas in air), have atoms of one element only.

The term “bond” applies to a continuous range of atomic interactions. However, we can categorize most bonds into distinct types based on their different properties. Which type forms depends on the atoms taking part in the molecule.

Ionic Bonds Two ions may stay together by the mutual attraction of their oppo- site charges, an association called an ionic bond. Ionic bonds can be quite strong. Ionically bonded sodium and chloride ions make sodium chloride (NaCl), which we know as table salt; a crystal of this substance consists of a lattice of sodium and chloride ions interacting in ionic bonds (Figure 2.8A).

Ions retain their respective charges when participating in an ionic bond (Figure 2.8B). Thus, one “end” of an ionically bonded molecule has a positive charge, and the other “end” has a negative charge. Any such separation of charge into distinct positive and negative regions is called polarity (Figure 2.8C).

Covalent Bonds In a covalent bond, two atoms share a pair of electrons, so each atom’s vacancy becomes partially filled (Figure 2.9). Sharing electrons links the two atoms, just as sharing a pair of earphones links two friends (left). Covalent bonds can be stronger than ionic bonds, but they are not always so.

Table 2.1 shows some of the different ways we represent molecules that are held together with covalent bonds. In structural formulas, a line between two atoms rep- resents a single covalent bond, in which two atoms share one pair of electrons. For example, molecular hydrogen (H2) has one covalent bond between hydrogen atoms (HsH).

Two, three, or even four covalent bonds may form between atoms when they share multiple pairs of electrons. For example, two atoms sharing two pairs of electrons are connected by two covalent bonds. Such double bonds are represented by a double line between the atoms. A double bond links the two oxygen atoms in molecular oxygen (O=O). Three lines indicate a triple bond, in which two atoms share three pairs of electrons. A triple covalent bond links the two nitrogen atoms in molecular nitrogen (N≡N).

Double and triple bonds are not distinguished from single bonds in structural models, which show positions and relative sizes of the atoms in three dimensions. The bonds are shown as one stick connecting two balls, which represent atoms. Ele- ments are usually coded by color:

Figure 2.7 the water molecule. each water molecule has two hydrogen atoms bonded to the same oxygen atom.

two hydrogen atoms

one oxygen atom

H H

Figure 2.8 ionic bonds in table salt, or naCl. (A) left, Francois Gohier/Science Source; top right, Melica/Shutterstock.

B. The strong mutual attraction of opposite charges holds a sodium ion and a chloride ion together in an ionic bond.

C. ions taking part in an ionic bond retain their charge, so the molecule itself is polar. One side is positively charged (represented by a blue overlay); the other side is nega- tively charged (red overlay).

a. Above, tiny crystals of sodium chloride compose table salt. right, each crystal consists of many sodium and chloride ions locked together in a cubic lattice by ionic bonds.

Na+ Cl–

positive charge

negative charge

+ +

+ – –

–

carbon hydrogen oxygen nitrogen phosphorus

ionic bond

11 17

11p+

10e–

charge: +1

Sodium ion Chloride ion

charge: –1

17p+

18e–

ionic bond

11 17

11p+

10e–

charge: +1

Sodium ion Chloride ion

charge: –1

17p+

18e–

MOLeCuLeS OF LiFe Chapter 2 29

Molecular hydrogen (Hs H) Two hydrogen atoms, each with one proton, share two electrons in a nonpolar covalent bond.

1 1

Molecular oxygen (O=O) Two oxygen atoms, each with eight protons, share four electrons in a double covalent bond.

1 1

Water (Hs Os H) Two hydrogen atoms share electrons with an oxygen atom in two covalent bonds. The bonds are polar because the oxygen exerts a greater pull on the shared electrons than the hydrogens do.

Atoms share electrons unequally in a polar covalent bond. A bond between an oxygen atom and a hydrogen atom in a water molecule is an example: One atom (the oxygen, in this case) pulls the electrons a little more toward its side of the bond, so that atom bears a slight negative charge. The atom at the other end of the bond (the hydrogen, in this case) bears a slight positive charge. Covalent bonds in most compounds are polar. By contrast, atoms participating in a nonpolar covalent bond share electrons equally. There is no difference in charge between the two ends of such bonds. Molecular hydrogen (H2), oxygen (O2), and nitrogen (N2) are examples.

2.4 Hydrogen Bonds and Water Life evolved in water. All living organisms are mostly water, many of them still live in it, and all of the chemical reactions of life are carried out in water-based fluids. What makes water so fundamentally important for life?

Water has unique properties that arise from the two polar covalent bonds in each water molecule. Overall, the molecule has no charge, but the oxygen atom

Common name Water Familiar term

Chemical name Dihydrogen monoxide Describes elemental composition.

Chemical formula H2O indicates unvarying proportions of elements. Subscripts show number of atoms of an element per molecule. The absence of a subscript means one atom.

Structural formula H s O s H represents each covalent bond as a single line between atoms.

Structural model Shows relative sizes and positions of atoms in three dimensions.

Shell model

1 1

Shows how pairs of electrons are shared in covalent bonds.

table 2.1 representing Covalent Bonds in Molecules

Take-Home Message 2.3 how do atoms interact in chemical bonds?

• A chemical bond forms between atoms when their electrons interact. Depending on the atoms taking part in it, the bond may be ionic or covalent.

• An ionic bond is a strong mutual attraction between ions of opposite charge. • Atoms share a pair of electrons in a covalent bond. When the atoms share

electrons unequally, the bond is polar.

Figure 2.9 Covalent bonds, in which atoms fill vacan- cies by sharing electrons. Two electrons are shared in each covalent bond. When sharing is equal, the bond is nonpolar. When one atom exerts a greater pull on the electrons, the bond is polar.

chemical bond An attractive force that arises between two atoms when their electrons interact. Links atoms into molecules.

compound Molecule that has atoms of more than one element.

covalent bond Type of chemical bond in which two atoms share a pair of electrons.

ionic bond Type of chemical bond in which a strong mutual attraction links ions of opposite charge.

polarity Any separation of charge into distinct posi- tive and negative regions.

30 Unit 1 HOW CeLLS WOrk

carries a slight negative charge, and the two hydrogen atoms carry a slight positive charge. Thus, the molecule itself is polar (Figure 2.10A).

The polarity of individual water molecules attracts them to one another. The slight positive charge of a hydrogen atom in one water molecule is drawn to the slight negative charge of an oxygen atom in another. This type of interaction is called a hydrogen bond. A hydrogen bond is an attraction between a covalently bonded hydrogen atom and another atom taking part in a separate polar covalent bond (Figure 2.10B). Like ionic bonds, hydrogen bonds form by the mutual attrac- tion of opposite charges. However, unlike ionic bonds, hydrogen bonds do not make molecules out of atoms, so they are not chemical bonds.

Hydrogen bonds lie on the weaker end of the spectrum of atomic interactions; they form and break much more easily than covalent or ionic bonds. Even so, many of them form, and collectively they can be quite strong. As you will see, hydrogen bonds stabilize the characteristic structures of biological molecules such as DNA and proteins. They also form in tremendous numbers among water molecules (Fig- ure 2.10C). Extensive hydrogen bonding among water molecules gives liquid water the special properties that make life possible.

Water Is an Excellent Solvent The polarity of the water molecule and its abil- ity to form hydrogen bonds make water an excellent solvent, which means that many other substances can dissolve in it. Substances that dissolve easily in water are hydrophilic (water-loving). Ionic solids such as sodium chloride (NaCl) dissolve in water because the slight positive charge on each hydrogen atom in a water molecule attracts negatively charged ions (Cl–), and the slight negative charge on the oxygen atom attracts positively charged ions (Na+). Hydrogen bonds among many water molecules are collectively stronger than an ionic bond between two ions, so the solid dissolves as water molecules tug the ions apart and sur- round each one (right).

When a substance such as NaCl dissolves, its component ions disperse uni- formly among the molecules of liquid, and it becomes a solute. Sodium chloride is called a salt because it releases ions other than H+ and OH– when it dissolves in water (more about this in the next section). A uniform mixture such as salt dissolved in water is called a solution. Chemical bonds do not form between molecules of sol- ute and solvent, so the proportions of the two substances in a solution can vary. The amount of a solute that is dissolved in a given volume of fluid is its concentration.

Many nonionic solids also dissolve easily in water. Sugars are examples. Molecules of these substances have one or more polar covalent bonds, and atoms participating in a polar covalent bond can form hydrogen bonds with water molecules. Hydrogen bonding with water pulls individual molecules of the solid away from one another and keeps them apart. Unlike ionic solids, these substances retain their molecular integrity when they dissolve, which means they do not dissociate into atoms.

Water does not interact with hydrophobic (water-dreading) substances such as oils. Oils consist of nonpolar molecules, and hydrogen bonds do not form between nonpolar molecules and water. When you mix oil and water, the water breaks into small droplets, but quickly begins to cluster into larger drops as new hydrogen bonds form among its molecules. The bonding excludes molecules of oil and pushes them together into drops that rise to the surface of the water. The very

H H

slight positive charge

slight negative charge

–

a hydrogen bond

O H

B. A hydrogen bond is an attraction between a hydrogen atom and another atom taking part in a separate polar covalent bond.

a. Polarity of the water molecule. each of the hydrogen atoms in a water molecule bears a slight positive charge (represented by a blue overlay). The oxygen atom carries a slight negative charge (red overlay).

C. The many hydrogen bonds that form among water molecules impart special properties to liquid water.

Figure 2.10 hydrogen bonds and water.

MOLeCuLeS OF LiFe Chapter 2 31

same interactions occur at the thin, oily membrane that separates the watery fluid inside cells from the watery fluid outside of them. Such interactions give rise to the structure of cell membranes.

Water Has Cohesion Molecules of some substances resist separating from one another, and the resistance gives rise to a property called cohesion. Water has cohesion because hydrogen bonds collectively exert a continuous pull on its individual molecules. You can see cohesion in water as surface tension, which means that the surface of liquid water behaves a bit like a sheet of elastic (left).

Cohesion is a part of many processes that sustain multicelled bodies. Consider how sweating helps keep your body cool during hot, dry weather. Sweat, which is about 99 percent water, cools the skin as it evaporates. Why?

Evaporation is the process in which molecules escape from the surface of a liquid and become vapor. Evaporation of water is resisted by hydrogen bonding among individual water molecules. In other words, overcoming water’s cohesion takes energy. Thus, evaporation sucks energy (in the form of heat) from liquid water, and this lowers the water’s surface temperature.

Another example of cohesion’s importance to life involves plants. Water molecules evaporate from leaves, and replacements are pulled upward from roots. Cohesion makes it possible for columns of liquid water to rise from roots to leaves inside narrow pipelines of vascular tissue. In some trees, these pipelines extend hundreds of feet above the soil (Section 27.4 returns to this topic).

Water Stabilizes Temperature All atoms jiggle nonstop, so the molecules they make up jiggle too. We measure the energy of this motion as degrees of temperature. Adding energy (in the form of heat, for example) makes the jiggling faster, so the temperature rises. Hydrogen bonding keeps water molecules from moving as much as they would otherwise, so it takes more heat to raise the tempera- ture of water compared with other liquids. Temperature stability is an important part of homeostasis because most of the molecules of life function properly only within a certain range of temperature.

Below 0°C (32°F), water molecules do not jiggle enough to break hydrogen bonds between them, and they become locked in the rigid, lattice-like bonding pattern of ice (Figure 2.11). Individual water molecules pack less densely in ice than they do in water, which is why ice floats on water. Sheets of ice that form on the surface of ponds, lakes, and streams can insulate the water under them from subfreezing air temperatures. Such “ice blankets” protect aquatic organisms during long, cold winters.

er be

rt Sc

hn ek

en bu

rg er

Take-Home Message 2.4 What gives water the special properties that make life possible?

• extensive hydrogen bonding among water molecules arises from the polarity of the individual molecules.

• Hydrogen bonding among water molecules imparts cohesion to liquid water, and gives it the ability to stabilize temperature and dissolve many substances.

Figure 2.11 ice. Top, hydrogen bonds lock water molecules in a rigid lat- tice in ice. The molecules in this lattice pack less densely than in liquid water (compare Figure 2.10C), so ice floats on water. Bottom, a covering of ice can insulate water underneath it, thus keeping aquatic organisms from freezing during harsh winters. Bottom, www.flickr.com/photos/roseofredrock.

cohesion Property of a substance that arises from the tendency of its molecules to resist separating from one another.

concentration Amount of solute per unit volume of solution.

evaporation Transition of a liquid to a vapor.

hydrogen bond Attraction between a covalently bonded hydrogen atom and another atom taking part in a separate covalent bond.

hydrophilic Describes a substance that dissolves easily in water.

hydrophobic Describes a substance that resists dis- solving in water.

salt ionic compound that releases ions other than H+ and OH– when it dissolves in water.

solute A dissolved substance.

solution uniform mixture of solute completely dis- solved in a solvent.

solvent Liquid in which other substances dissolve.

temperature Measure of molecular motion.

32 Unit 1 HOW CeLLS WOrk

2.5 Acids and Bases A hydrogen atom, remember, is just a proton and an electron. When a hydrogen atom participates in a polar covalent bond, the electron is pulled away from the proton, just a bit. Hydrogen bonding in water tugs on that proton even more, so much that the proton can be pulled right off of the molecule. The electron stays with the rest of the molecule, which becomes negatively charged (ionic), and the proton becomes a hydrogen ion (H+). For example, a water molecule that loses a proton becomes a hydroxyl ion (OH–). The loss is more or less temporary, because these two ions easily get back together to form a water molecule (H2O). With other molecules, the loss of a hydrogen ion in water is essentially permanent.

We use a value called pH to measure of the number of hydrogen ions in a water- based fluid. In pure water, the number of H+ ions is the same as the number of OH– ions, and the pH is 7, or neutral. The higher the number of hydrogen ions, the lower the pH. A one-unit decrease in pH corresponds to a tenfold increase in the number of H+ ions (Figure 2.12). One way to get a sense of the pH scale is to taste dissolved baking soda (pH 9), distilled water (pH 7), and lemon juice (pH 2).

An acid is a substance that gives up hydrogen ions in water. Acids can lower the pH of a solution and make it acidic (below pH 7). Bases accept hydrogen ions from water, so they can raise the pH of a solution and make it basic (above pH 7). Nearly all of life’s chemistry occurs near pH 7. Under normal circumstances, fluids inside cells and bodies stay within a certain range of pH because they are buffered. A buffer is a set of chemicals that can keep pH stable by alternately donating and accepting ions that affect pH. For example, two chemicals, carbonic acid and bicarbonate, are part of a homeostatic mechanism that normally keeps your blood pH between 7.3 and 7.5. Carbonic acid forms when carbon dioxide gas dissolves in the fluid portion of blood. It can dissociate into a hydrogen ion and a bicarbonate ion, which in turn recombine to form carbonic acid:

H+ �H2CO3

carbonic acid

H2CO3

carbonic acid

HCO3 –

bicarbonate

An excess of OH– ions in the blood causes the carbonic acid in it to release H+ ions. These combine with the excess OH– ions to form water, which does not affect pH. Excess H+ in blood combines with the bicarbonate, so it does not affect pH either.

Any buffer can neutralize only so many ions. Even slightly more than that limit and the pH of the fluid will change dramatically. Buffer failure can be catastrophic in a biological system because most biological molecules can function properly only within a narrow range of pH. Consider what happens when breathing is impaired suddenly. Carbon dioxide gas accumulates in tissues, and too much carbonic acid forms in blood. If the excess acid reduces blood pH below 7.3, a dangerous level of unconsciousness called coma can be the outcome.

— 14

— 13

— 12

— 11

— 10

— 9

— 8

— 7

— 6

— 5

— 4

— 3

— 2

— 1

— 0

m o

re a

ci d

ic m

o re

b as

cola

beer

corn

milk

battery acid

gastric fluid

acid rain lemon juice

vinegar

orange juice tomatoes, wine bananas

bread black coffee urine, tea, typical rain

butter

pure water

blood, tears egg white seawater

baking soda detergents Tums

toothpaste hand soap milk of magnesia

household ammonia

hair remover

bleach

oven cleaner

drain cleaner

Figure 2.12 a ph scale. Here, red dots signify hydrogen ions (H+) and blue dots signify hydroxyl ions (OH–). Also shown are the approxi- mate pH values for some common solutions.

This pH scale ranges from 0 (most acidic) to 14 (most basic). A change of one unit on the scale corresponds to a tenfold change in the amount of H+ ions. Photos, © JupiterImages Corporation.

answer: 2.5

Figure it Out: What is the approximate pH of cola?

Take-Home Message 2.5 Why are hydrogen ions important in biological systems?

• The number of hydrogen ions in a fluid determines its pH. Most biological systems function properly only within a narrow range of pH. Buffers help keep pH stable.

• Acids release hydrogen ions in water; bases accept them.

MOLeCuLeS OF LiFe Chapter 2 33

acid Substance that releases hydrogen ions in water.

base Substance that accepts hydrogen ions in water.

buffer Set of chemicals that can keep the pH of a solution stable by alternately donating and accepting ions that contribute to pH.

monomer Molecule that is a subunit of polymers.

organic Describes a compound that consists mainly of carbon and hydrogen atoms.

ph Measure of the amount of hydrogen ions in a fluid.

polymer Molecule that consists of multiple monomers.

2.6 Organic Molecules The same elements that make up a living body also occur in nonliving things, but their proportions differ. For example, compared to sand or seawater, a human body has a much larger proportion of carbon atoms. Why? Unlike sand or seawater, a body contains a lot of the molecules of life—complex carbohydrates and lipids, proteins, and nucleic acids—and these molecules consist of a high proportion of carbon atoms. Compounds that consist primarily of carbon and hydrogen atoms are said to be organic. The term is a holdover from a time when such molecules were thought to be made only by living things, as opposed to the “inorganic” molecules that formed by nonliving processes. We now know that organic compounds were present on Earth long before organisms were.

Carbon’s importance to life arises from its ver- satile bonding behavior. Carbon has four vacancies in its outer shell, so it can form four covalent bonds with other atoms, including other carbon atoms. Many organic molecules have a chain of carbon atoms, and this backbone often forms rings (Figure 2.13). Small molecular groups that attach to the backbone impart chemical properties to the mole- cule. For example, carboxyl groups (—COOH) make amino acids and fatty acids acidic; hydroxyl groups (—OH) make sugars polar. Carbon’s ability to form chains and rings, and also to bond with many other elements, means that atoms of this element can be assembled into a wide variety of organic compounds.

As you will see shortly, the function of an organic molecule depends on its structure. The structure of even a small organic molecule can be quite complicated (Figure 2.14A), so representations are typically simplified. Hydrogen atoms and some of the bonds may not be shown, but are understood to exist where they should. Carbon rings such as the ones that occur in glucose and other sugars are

often depicted as polygons (Figure 2.14B). If no atom is shown at a corner or at the end of a bond, a carbon is implied there. Ball-and-stick models are used to depict an organic molecule’s three-dimensional arrangement of atoms (Figure 2.14C); space-filling models are used to show its overall shape (Figure 2.14D). Proteins and nucleic acids are often modeled as ribbon structures, which, as you will see in Sec- tion 2.9, show how the molecule folds and twists.

What Cells Do to Organic Compounds All biological systems are based on the same organic molecules, but the details of those molecules differ among organisms. Just as atoms bonded in different numbers and arrangements form dif- ferent molecules, simple organic building blocks bonded in different numbers and arrangements form different versions of the molecules of life.

Cells assemble complex carbohydrates, lipids, proteins, and nucleic acids from small organic molecules. These small organic molecules—sugars, fatty acids, amino acids, and nucleotides—are called monomers when they are used as subunits of larger molecules. A molecule that consists of multiple monomers is a poly- mer. Cells build polymers from monomers, and break down polymers to release

Figure 2.14 Structural models of an organic molecule. All of these models represent the same molecule: glucose.

a. A structural formula for an organic molecule—even a simple one—can be very com- plicated. The overall structure is obscured by detail.

C. A ball-and-stick model shows the arrangement of atoms and bonds in three dimensions.

glucose

CH2OH

B. Structural formulas of organic molecules are often simplified

by using polygons as symbols for rings, and omitting some bonds and element labels.

CH2OH

D. A space-filling model can be used to show a mole- cule’s overall shape. individual atoms are visible in this model. Space-filling models of larger molecules often show only the surface contours.

glucose

C C

O C

O O

H H

a. Carbon’s versatile bonding behavior allows it to form a variety of structures, including rings.

B. Carbon rings form the backbone of many sugars, starches, and fats, such as those found in foods.

Figure 2.13 Carbon rings. (B) Getty Images.

34 Unit 1 HOW CeLLS WOrk

monomers. These and other processes of molecular change are called reactions. Cells constantly run reactions as they acquire and use energy to stay alive, grow, and reproduce—activities collectively called metabolism (Figure 2.15A). Metabolism also requires enzymes, which are organic molecules (usually proteins) that speed up reactions without being changed by them. For example, in a common reaction called condensation, an enzyme covalently bonds two monomers together (Fig- ure 2.15B). In hydrolysis, the reverse of condensation, an enzyme splits an organic polymer into its component monomers (Figure 2.15C).

2.7 Carbohydrates A carbohydrate is an organic compound that consists of carbon, hydrogen, and oxygen in a 1:2:1 ratio. The term can apply to a sugar molecule or a polymer of them, so these compounds are also called saccharides (saccharide means sugar). Cells use different kinds for fuel, as structural materials, and for storing energy.

Monosaccharides (one sugar) are the simplest carbohydrates, and common types have a backbone of five or six carbon atoms. Glucose, shown in Figure 2.14, is a monosaccharide. Sucrose, which is our table sugar, is a disaccharide (two sugars) that consists of glucose and fructose monomers. Monosaccharides and disaccha- rides are very soluble in water, so they can move easily through the water-based internal environments of all organisms.

Breaking the bonds of a monosaccharide releases energy that can be harnessed to power other reactions (Chapter 5 returns to this topic). Monosaccharides are also remodeled into other important compounds. For example, cells of plants and many animals make vitamin C from glucose. Human cells are unable to make vitamin C, so we need to get it from our food.

Foods that we call “complex” carbohydrates consist mainly of polysaccharides, which are chains of hundreds or thousands of monosaccharide monomers. The chains may be straight or branched, and can have one or many types of monosac- charides. The most common polysaccharides are cellulose, starch, and glycogen. All consist only of glucose monomers, but as substances their properties are very different. Why? The answer begins with differences in patterns of covalent bonding that link their monomers.

Cellulose, the major structural material of plants, is the most abundant organic molecule on Earth. Hydrogen bonding locks its long, straight chains of covalently bonded glucose monomers into tight, sturdy bundles (Figure 2.16A). The bundles form tough fibers that act like reinforcing rods inside stems and other plant parts, helping these structures resist wind and other forms of mechanical stress. Cellulose

C. Cells use a water- requiring reaction called hydrolysis to split a large molecule into smaller ones. An enzyme attaches a hydroxyl group and a hydrogen atom (both from water) at the cleavage site.

O +

OH HO+

HsOsH

B. Cells often build a large molecule from small ones by conden- sation. in this reaction, an enzyme removes a hydroxyl group from one molecule and a hydrogen atom from another. A covalent bond forms between the two molecules; water forms too.

O +

OH HO+

HsOsH

a. Metabolism refers to processes by which cells acquire and use energy as they make and break down molecules. Humans and other con- sumers break down the molecules in food. Their cells use energy and raw materials from the break- down to maintain themselves and to build new components.

Figure 2.15 Metabolism. Two common reactions by which cells build and break down organic molecules are shown.

Take-Home Message 2.6 how are all of the molecules of life alike?

• The molecules of life (carbohydrates, lipids, proteins, and nucleic acids) are organic, which means they consist mainly of carbon and hydrogen atoms.

• The structure of an organic molecule starts with a chain of carbon atoms (the back- bone) that may form one or more rings.

• By processes of metabolism, cells assemble the molecules of life from monomers. They also break apart polymers into component monomers.

Exactostock/SuperStock.

MOLeCuLeS OF LiFe Chapter 2 35

C. Glycogen functions as an energy reservoir in animals, including people. it is especially abundant in the liver and muscles. Above, glycogen consists of highly branched chains of glucose monomers.

a. Cellulose is the main structural component of plants. Above, in cellulose, hydrogen bonds stabilize chains of glucose monomers in tight bundles that form long fibers. Few organisms can digest this tough, insoluble material.

carbohydrate Molecule that consists primarily of carbon, hydrogen, and oxygen atoms in a 1:2:1 ratio.

cellulose Tough, insoluble carbohydrate that is the major structural material in plants.

enzyme Organic molecule that speeds up a reaction without being changed by it.

metabolism All the enzyme-mediated chemical reac- tions by which cells acquire and use energy as they build and break down organic molecules.

reaction Process of molecular change.

is insoluble (it does not dissolve) in water, and it is not easily broken down. Some bacteria and fungi make enzymes that can break it apart into its component sugars, but humans and other mammals do not. Dietary fiber, or “roughage,” usually refers to the indigestible cellulose in our vegetable foods. Bacteria that live in the guts of termites and grazers such as cattle and sheep help these animals digest the cellulose in plants. (Chapter 23 returns to the topic of animal digestion.)

In starch, a different covalent bonding pattern between glucose monomers makes a chain that coils up into a spiral (Figure 2.16B). Like cellulose, starch does not dissolve readily in water, but it is easier to break down. These properties make the molecule ideal for storing sugars in the watery, enzyme-filled interior of plant cells. Most plant leaves make glucose during the day, and their cells store it by build- ing starch. At night, hydrolysis enzymes break the bonds between starch’s glucose monomers. The released glucose can be broken down immediately for energy, or converted to sucrose that is transported to other parts of the plant. Humans also have hydrolysis enzymes that break down starch, so this carbohydrate is an impor- tant component of our food.

Animals store sugars in the form of glycogen, a polysaccharide that consists of highly branched chains of glucose monomers (Figure 2.16C). Muscle and liver cells contain most of the body’s glycogen. When the blood sugar level falls, liver cells break down the glycogen, and the released glucose subunits enter the blood.

Figure 2.16 three of the most common complex carbohydrates and their locations in a few organisms. each polysaccharide consists only of glucose units, but different bonding patterns that link the subunits result in substances with very different properties. Middle photo, © JupiterImages Corporation.

O O

Take-Home Message 2.7 What is a carbohydrate?

• Cells use simple carbohydrates (sugars) for energy and to build other molecules. • Sugar monomers, bonded different ways, form complex carbohydrates such as cel-

lulose, starch, and glycogen.

B. Starch is the main energy reserve in plants, which store it in their roots, stems, leaves, seeds, and fruits. Below, starch consists of long, coiled chains of glucose monomers.

36 Unit 1 HOW CeLLS WOrk

2.8 Lipids Lipids are fatty, oily, or waxy organic compounds. They vary in structure, but all are hydrophobic. Many lipids incorporate fatty acids, which are small organic mol- ecules that consist of a carbon chain “tail” of variable length, and a carboxyl group “head” (Figure 2.17). The tail is hydrophobic (hence the name “fatty”); the carboxyl group makes the head hydrophilic (and acidic). You are already familiar with the properties of fatty acids because these molecules are the main component of soap. The hydrophobic tails of fatty acids in soap attract oily dirt, and the hydrophilic heads dissolve the dirt in water.

Saturated fatty acids have only single bonds linking the carbons in their tails. In other words, their carbon chains are fully saturated with hydrogen atoms (Fig- ure 2.17A). The tail of a saturated fatty acid is flexible and it wiggles freely. Double bonds between carbons limit the flexibility of the tails of an unsaturated fatty acid (Figure 2.17B,C). These bonds are cis or trans, depending on the way the hydrogens are arranged around them (Figure 2.17D,E).

Fats The carboxyl group head of a fatty acid can easily form a covalent bond with another molecule. When it bonds to a glycerol, a type of alcohol, it loses its hydro- philic character. Three fatty acids bonded to the same glycerol form a triglyceride, a molecule that is entirely hydrophobic and therefore does not dissolve in water. Triglycerides are the most abundant and richest energy source in vertebrate bodies; gram for gram, they store more energy than carbohydrates.

A fat is a substance that consists mainly of triglycerides. Butter and other fats derived from animals have a high proportion of triglycerides in which all three fatty acid tails are saturated. These triglycerides are commonly called saturated fats, and substances that consist of them are solid at room temperature because floppy

saturated fatty acid tails can pack tightly together. Vegetable oils, by contrast, have a high proportion of unsaturated fats, the common term for triglycerides in which at least one of the three fatty acid tails is unsaturated. Each double bond makes a rigid kink, and kinky tails cannot pack tightly. This is why most substances that consist of unsaturated fats are liquid at room temperature. The partially hydrogenated vegetable oils that you learned about in Section 2.1 are an exception. They are solid at room temperature because the special trans double bond keeps their fatty acid tails straight, allowing them to pack tightly just like saturated fatty acid tails do.

Phospholipids A phospholipid has two fatty acid tails and a head that contains a phosphate group (Figure 2.18A). The tails are hydrophobic, but the phosphate group is highly polar and it makes the head very hydrophilic. These opposing properties give rise to the basic structure of cell membranes,

H—C—H

C O OH

H—C—H

C—H

C O OH

H—C—H

C—H

H—C—H

C—H

H—C—H

C O OH

H—C—H

C—H

H—C—H

C—H

H—C—H

C—H

H—C—H

C O OH

H—C—H

H—C

C—H

H—C—H

C O OH

a. stearic acid (saturated)

B. linoleic acid (omega-6)

C. linolenic acid (omega-3)

D. oleic acid (cis)

e. elaidic acid (trans)

hydrophilic “head”

hydrophobic “tail”

Figure 2.17 Fatty acids. Double bonds in the tails are highlighted in red.

a. The tail of stearic acid is fully saturated with hydrogen atoms.

B. Linoleic acid, with two double bonds, is unsaturated. The first double bond occurs at the sixth carbon from the end of the tail, so linoleic acid is called an omega-6 fatty acid. Omega-6 and C omega-3 fatty acids are “essential fatty acids,” which means your body does not make them and they must come from food.

D. The hydrogen atoms around the double bond in oleic acid are on the same side of the tail. Most other naturally occurring unsaturated fatty acids have these cis bonds.

e. Hydrogenation creates abundant trans bonds, with hydrogen atoms on opposite sides of the tail.

answer: cis

Figure it Out: Are the double bonds in linolenic acid cis or trans?

MOLeCuLeS OF LiFe Chapter 2 37

fat Substance that consists mainly of triglycerides.

fatty acid Organic compound with an acidic carboxyl group “head” and a long carbon chain “tail.”

lipid Fatty, oily, or waxy organic compound.

lipid bilayer Double layer of lipids arranged tail-to- tail; structural foundation of all cell membranes.

phospholipid A lipid with a phosphate group in its hydrophilic head, and two nonpolar fatty acid tails.

saturated fatty acid Fatty acid with only single bonds linking the carbons in its tail.

steroid A type of lipid with four carbon rings and no fatty acid tails.

triglyceride A molecule with three fatty acid tails that is entirely hydrophobic; main component of fats.

unsaturated fatty acid Fatty acid with one or more carbon–carbon double bonds in its tail.

wax Water-repellent substance that is a complex, varying mixture of lipids.

which consist mainly of phospholipids. In a cell membrane, phospholipids are arranged in two layers—a lipid bilayer (Figure 2.18B). The heads of one layer are dissolved in the cell’s watery interior, and the heads of the other layer are dissolved in the cell’s fluid surroundings. All of the hydrophobic tails are sandwiched between the hydrophilic heads. Section 3.3 returns to the structure of cell membranes.

Waxes A wax is a complex, varying mixture of lipids with long fatty acid tails bonded to carbon rings or other structures. These molecules pack tightly, so waxes are firm and water-repellent. Plants secrete waxes onto their exposed surfaces to

restrict water loss and keep out parasites and other pests. Other types of waxes protect, lubricate, and soften skin and hair. Waxes, together with fats and fatty acids, make feathers waterproof. Bees store honey and raise new generations of bees inside a honeycomb of secreted beeswax.

Steroids Steroids are lipids with no fatty acid tails; they have a rigid backbone that consists of twenty carbon atoms arranged in a characteristic pattern of four rings (Figure 2.19). As you will see in later chapters, these molecules serve varied and important physiological functions in plants, fungi, and animals. Cholesterol, the most common steroid in animal tissues, is remodeled into other molecules such as bile salts (which help digest fats), vitamin D (required to keep teeth and bones strong), and steroid hormones.

Take-Home Message 2.8 What are lipids?

• Lipids are fatty, waxy, or oily organic compounds. • Fats are substances that consist primarily of triglycerides, which have three fatty acid

tails. Triglycerides are called unsaturated fats if there are double bonds in one or more of their fatty acid tails, and saturated fats if there are none.

• Phospholipids arranged in a lipid bilayer are the main component of cell membranes. • Waxes have complex, varying structures. They are components of water-repelling and

lubricating secretions. • Steroids serve varied and important physiological roles in plants, fungi, and animals.

Figure 2.18 phospholipids as components of cell membranes.

Figure 2.19 examples of steroids. estrogen and testosterone are steroid hormones that govern reproduction and secondary sexual traits in animals. These hormones give rise to the gender- specific traits of many species, including wood ducks. Bottom, Tim Davis/Science Source.

male female

an estrogen testosterone

a. The two fatty acid tails of a phospholipid are attached to a phosphate- containing head.

C—O—P—O—C—C—N—CH3

H—C—H

C—H

H—C—H

C—H

H—C—H

H—C

H H

CH3

CH3O-

C O

phosphate group

hydrophilic head one layer

of lipids

one layer of lipids

two hydrophobic tails

B. A double layer of phospholipids—the lipid bilayer—is the structural foundation of all cell membranes.

38 Unit 1 HOW CeLLS WOrk

2.9 Proteins

Cells make the thousands of different proteins they need from only twenty kinds of amino acid monomers. An amino acid is a small organic compound with an amine group (sNH2), a carboxyl group (—COOH, the acid), and a side chain called an “R group” that defines the kind of amino acid. In most amino acids, all three groups are attached to the same carbon atom:

OHH amine group

carboxyl group

R group

The covalent bond that links amino acids in a protein is called a peptide bond. During protein synthesis, a peptide bond forms between the carboxyl group of the first amino acid and the amine group of the second (Figure 2.20

). Another peptide bond links a third amino acid to the second, and so on (you will learn more about the details of protein synthesis in Chapter 7). A short chain of amino acids is called a peptide; as the chain lengthens, it becomes a polypeptide. Polypeptides can be hundreds or even thousands of amino acids long.

The idea that structure dictates function is particularly appropriate as applied to proteins, because the diversity in biological activity among these molecules arises from differences in their three-dimensional shape. Protein structure begins with the linear series of amino acids composing a polypeptide

. The order of the amino acids, which is called primary structure, defines the type of protein.

The molecule begins to take on three-dimensional shape during protein syn- thesis, as hydrogen bonds that form between amino acids cause the lengthening polypeptide to twist and fold. Hydrogen bonding holds sections of the polypeptide in loops, helices (coils), or flat sheets, and these patterns constitute the protein’s secondary structure

. The primary structure of each type of protein is unique, but most proteins have similar patterns of secondary structure.

Much as an overly twisted rubber band coils back upon itself, hydrogen bond- ing also makes the loops, helices, and sheets of a protein fold up into even more compact domains. These domains are called tertiary structure. Tertiary structure is what makes a protein a working molecule. For example, the helices and loops in a polypeptide called a globin chain fold up together to form a pocket

. This pocket

CH3

valine

sOHHs

methionine

CH2

Hs sOH

CH3

methionineHC

CH3

sOH

valinemethionine

CH2

CH3

proline glutaglutatamicc aciacacaacacacacicacacciaciiiciciiiiaa iiiiiaciiiciacccciiaacaccciciiiicciiiiacciiciciciiciaaciiiacaccciiiaaacciiiaaaccccciiiicciiia iaaccciiiaacciiccccicciiddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddvaline histidine leucine threonineHC

CH3

valine

sOHHs

methionine

CH2

Hs sOH

CH3

methionineHC

CH3

sOH

valinemethionine

CH2

CH3

glutaglutatamicc aciacacaacacacacicacacciaciiiciciiiiaa iiiiiaciiiciacccciiaacaccciciiiicciiiiacciiciciciiciaaciiiacaccciiiaaacciiiaaaccccciiiicciiia iaaccciiiaacciiccccicciiddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddvaline histidine leucine threonine

A protein’s primary structure consists of a linear sequence of amino acids (a polypeptide). each type of protein has a unique primary structure.

CH3

valine

sOHHs

methionine

CH2

Hs sOH

CH3

methionineHC

CH3

sOH

valinemethionine

CH2

CH3

valine

sOHHs

methionine

CH2

Hs sOH

CH3

methionineHC

CH3

sOH

valinemethionine

CH2

CH3

A condensation reaction joins the carboxyl group of one amino acid and the amine group of another to form a peptide bond. in this example, a peptide bond forms between the amino acids methionine and valine.

Figure 2.20 how protein structure arises. (3–5) 1BBB, A third quaternary structure of human hemoglobin A at 1.7-A resolution. Silva, M.M., Rogers, P.H., Arnone, A., Journal: (1992) J.Biol.Chem. 267: 17248-17256.

Figure 2.21 an example of a protein domain. This barrel domain is part of a rotary mechanism in a larger protein. The protein is a molecular motor that pumps hydrogen ions through cell membranes. pdb ID2W5J, Vollmar, M., Shlieper, D., Winn, M., Buechner, C., Groth, G. “Structure of the C14 rotor ring of the proton translocating chloroplast ATP synthase.” (2009) J. Biol. Chem. 284:18228.

MOLeCuLeS OF LiFe Chapter 2 39

amino acid Small organic compound that is a subunit of proteins. Consists of a carboxyl group, an amine group, and a characteristic side group (r), all typically bonded to the same carbon atom.

denature To unravel the shape of a protein or other large biological molecule.

peptide bond A bond between the amine group of one amino acid and the carboxyl group of another. Joins amino acids in proteins.

protein Polymer of amino acids; an organic molecule that consists of one or more polypeptides.

holds a heme, which is a small compound essential to the function of the finished protein—hemoglobin. In other proteins, sheets, loops, and helices come together as complex structures that resemble barrels, propellers, sandwiches, and so on. Barrel domains often form tunnels through cell membranes, allowing small molecules to cross. Some proteins have barrel domains that rotate like motors in small molecular machines (Figure 2.21). A protein may have several domains, each contributing a particular structural or functional property to the molecule.

Many proteins also have quaternary structure, which means they consist of two or more polypeptides that are closely associated or covalently bonded together. Hemoglobin is like this

. So are most enzymes, which have multiple polypeptides that collectively form a roughly spherical shape.

Fibrous proteins aggregate by many thousands into much larger structures, with their polypeptides organized into strands or sheets. The keratin in your hair is an example

. Other fibrous proteins are part of the mechanisms that help cells, cell parts, and multicelled bodies move.

Carbohydrates, lipids, or both may get attached to a protein after synthesis. A protein with carbohydrates attached to it is called a glycoprotein. Molecules that allow a body to recognize its own cells are glycoproteins, as are other molecules that help cells interact in immunity. A protein with one or more lipids attached to it is called a lipoprotein. Some lipoproteins are aggregate structures that consist of vari- able amounts and types of proteins and lipids (Figure 2.22).

The Importance of Protein Structure Protein shape depends on hydrogen bonds and other interactions that heat, some salts, shifts in pH, or detergents can disrupt. Such disruption can cause proteins to lose their three-dimensional shape, or denature. Once a protein’s shape unravels, so does its function. You can see denaturation in action when you cook an egg. A protein called albumin is a major component of egg white. Cooking does not disrupt the covalent bonds of albu- min’s primary structure, but it does destroy the hydrogen bonds that maintain the protein’s shape. When a translucent egg white turns opaque, the albumin has been denatured. For a very few proteins, denaturation is reversible if normal conditions return, but albumin is not one of them. There is no way to uncook an egg.

Diseases such as bovine spongiform encephalitis (BSE, or mad cow disease) in cattle, Creutzfeldt–Jakob disease in humans, and scrapie in sheep, are the dire aftermath of a protein that changes shape. These diseases may be inherited, but

Tertiary structure arises when loops, helices, and sheets fold up into a domain. in this example, the helices of a globin chain form a pocket.

Many proteins have two or more polypeptides (quaternary structure). Hemoglobin, shown here, consists of four globins ( green and blue). The pocket of each globin now holds a heme group (red ).

Some types of proteins can aggregate into much larger structures. As an example, organized arrays of keratin, a fibrous protein, compose very long filaments that make up your hair.

CH3

valine

sOHHs

methionine

CH2

Hs sOH

CH3

methionineHC

CH3

sOH

valinemethionine

CH2

CH3

Secondary structure arises as a polypeptide chain twists into a helix (coil), loop, or sheet held in place by hydrogen bonds.

CH3

valine

sOHHs

methionine

CH2

Hs sOH

CH3

methionineHC

CH3

sOH

valinemethionine

CH2

CH3

valine

sOHHs

methionine

CH2

Hs sOH

CH3

methionineHC

CH3

sOH

valinemethionine

CH2

CH3

valine

sOHHs

methionine

CH2

Hs sOH

CH3

methionineHC

CH3

sOH

valinemethionine

CH2

CH3

protein

lipids

Figure 2.22 a lipoprotein particle. The one depicted here (HDL, which is often called “good” cholesterol) consists of thousands of lipids lassoed into a clump by two proteins. Castrignanò T, De Meo PD, Cozzetto D, Talamo IG, Tramontano A. (2006). The PMDB Protein Model Database. Nucleic Acids Research, 34: D306–D309.

40 Unit 1 HOW CeLLS WOrk

more often they arise spontaneously. All are characterized by relentless deterioration of mental and physical abilities that eventually causes death (Figure 2.24A), and all begin with a glycoprotein called PrPC that occurs normally in cell membranes of the mammalian body. This protein is especially abundant in brain cells, but we still know very little about what it does. Sometimes, a PrPC protein misfolds so that part of the molecule forms a sheet instead of a helix. One misfolded molecule should not pose much of a threat, but when this particular protein misfolds it becomes a prion, or infectious protein. The shape of a misfolded PrPC protein causes normally folded PrPC proteins to misfold too. Each protein that misfolds becomes infectious, so the number of prions increases exponentially.

The shape of misfolded PrPC proteins allows them to align tightly into long, insoluble fibers that are called amyloid fibrils. Amyloid fibrils grow from their ends as more PrPC proteins misfold (Figure 2.24B). They form patches in the brain that disrupt its function, causing symptoms such as confusion, memory loss, and lack of coordination. Holes form in the brain as its cells die. Eventually, the brain becomes so riddled with holes that it looks like a sponge.

In the mid-1980s, an epidemic of mad cow disease in Britain was followed by an outbreak of a new variant of Creutzfeldt–Jakob disease (vCJD) in humans. Researchers isolated a prion similar to the one in scrapie-infected sheep from cows with BSE, and also from humans affected by the new type of Creutzfeldt–Jakob disease. How did the prion get from sheep to cattle to people? Prions resist denatur- ation, so treatments such as cooking that inactivate other types of infectious agents have little effect on them. The cattle became infected by the prion after eating feed prepared from the remains of scrapie-infected sheep, and people became infected by eating beef from the infected cattle.

Two hundred people have died from vCJD since 1990. The use of animal parts in livestock feed is now banned in many countries, and the number of cases of BSE

Digging Into Data effects of Dietary Fats on Lipoprotein Levels

Cholesterol that is made by the liver or that enters the body from food does not dissolve in blood, so it is carried through the bloodstream by lipoproteins. Low-density lipoprotein (LDL) carries cholesterol to body tissues such as artery walls, where it can form deposits associated with cardiovascular disease. Thus, LDL is often called “bad” cholesterol. High- density lipoprotein (HDL) carries cholesterol away from tissues to the liver for disposal, so HDL is often called “good” cholesterol. in 1990, ronald Mensink and Martijn katan published a study that tested the effects of different dietary fats on blood lipoprotein levels. Their results are shown in Figure 2.23.

1. in which group was the level of LDL (“bad” cholesterol) highest? 2. in which group was the level of HDL (“good” cholesterol) lowest? 3. An elevated risk of heart disease has been correlated with increasing

LDL-to-HDL ratios. rank the three diets according to their predicted effect on cardiovascular health.

Figure 2.23 effect of diet on lipoprotein levels. researchers placed 59 men and women on a diet in which 10 per- cent of their daily energy intake consisted of cis fatty acids, trans fatty acids, or saturated fats. Blood LDL and HDL levels were mea- sured after three weeks on the diet; averaged results are shown in mg/dL (milligrams per deciliter of blood). All subjects were tested on each of the diets. The ratio of LDL to HDL is also shown. Source, Mensink RP, Katan MB, “Effect of dietary trans fatty acids on high-density and low-density lipoprotein cholesterol levels in healthy subjects.” NEJM 323(7):439–45.

Figure 2.24 Variant Creutzfeldt–Jakob disease (vCJD). (A) © Gary I. Rothstein/Reuters/Corbis; (B) Sherif Zaki, MD, PhD, Wun-Ju Shieh, MD, PhD, MPH/CDC.

a. Charlene Singh was one of the three people who developed symptoms of vCJD disease while living in the united States. Singh, like the others, most likely contracted the disease else- where; she spent her child- hood in Britain. Diagnosed in 2001, she died in 2004.

B. Slice of brain tissue from a person with vCJD. Fibers of prion proteins (amyloid fibrils) radiating from several deposits are visible.

Main Dietary Fats

cis fatty acids

103

1.87

optimal level

<100

>40

trans fatty acids

117

2.44

saturated fats

121

2.2

LDL

HDL

ratio

MOLeCuLeS OF LiFe Chapter 2 41

Take-Home Message 2.9 Why is protein structure important?

• A protein consists of one or more polypeptides, each a chain of amino acids. The order of amino acids in the polypeptide(s) dictates the type of protein.

• During protein synthesis, polypeptides twist and fold into coils, sheets, and loops, which fold and pack further into functional domains.

• A protein’s function arises from and depends on its three-dimensional shape.

Take-Home Message 2.10 What are nucleotides and nucleic acids?

• Nucleotides are monomers of the nucleic acids DNA and rNA. Some have additional roles. ATP, for example, is an important energy carrier in cells.

• DNA holds information necessary to build cells and multicelled individuals. • rNAs carry out protein synthesis.

atp Nucleotide monomer of rNA; also serves an important role as an energy carrier in cells.

Dna Deoxyribonucleic acid. Nucleic acid that consists of two chains of nucleotides twisted into a double helix; holds hereditary information.

nucleic acid Chain of nucleotides; DNA or rNA.

nucleotide Small molecule with a five-carbon sugar, a nitrogen-containing base, and one, two, or three phosphate groups. Monomer of nucleic acids; some have additional roles.

prion infectious protein.

rna ribonucleic acid. Nucleic acid that consists of a chain of nucleotides. Carries out protein synthesis.

2.10 Nucleic Acids Nucleotides are small organic molecules that function as energy carriers, enzyme helpers, chemical messengers, and subunits of DNA and RNA. Each consists of a monosaccharide ring bonded to a nitrogen-containing base and one, two, or three phosphate groups (Figure 2.25A). The monosaccharide is a five-carbon sugar, either ribose or deoxyribose, and the base is one of five compounds with a flat ring structure (we return to the structure of nucleotide bases in Section 6.2). When the third phosphate group of a nucleotide is transferred to another molecule, energy is transferred along with it. You will read about such phosphate-group transfers and their important metabolic role in Section 4.4. The nucleotide ATP (adenosine triphosphate) serves an especially important role as an energy carrier in cells.

Nucleic acids are chains of nucleotides in which the sugar of one nucleotide is joined to the phosphate group of the next (Figure 2.25B). An example is RNA, or ribonucleic acid, named after the ribose sugar of its component nucleotides. An RNA molecule is a chain of four kinds of nucleotide monomers (one of which is ATP). There are different types of RNA, and they work together to carry out protein synthesis. DNA, or deoxyribonucleic acid, is a nucleic acid named after the deoxy- ribose sugar of its component nucleotides. A DNA molecule consists of two chains of nucleotides twisted into a double helix (Figure 2.25C). Hydrogen bonds hold the chains together (Chapter 6 returns to DNA structure). Each cell starts life with DNA inherited from a parent cell. That DNA contains all of the information necessary to build a new cell and, in the case of multicelled organisms, an entire individual. The cell uses the order of nucleotide bases in DNA—the DNA sequence—to guide production of RNA and proteins (Chapter 7 returns to this topic).

and vCJD has since declined. Cattle with BSE still turn up, but so rarely that they pose little threat to human populations.

C. DNA consists of two chains of nucleotides, twisted into a double helix. Hydrogen bonding maintains the three-dimensional structure of this nucleic acid.

B. A chain of nucleotides is a nucleic acid. The sugar of one nucleotide is covalently bonded to the phosphate group of the next, forming a sugar–phosphate backbone.

a. example of a nucleotide: ATP. ATP is a monomer of rNA, and also a participant in many metabolic reactions.

Figure 2.25 nucleic acid structure.

NH2

C N

CHC N

CH2

PPP

ribose sugar

phosphate groups

base (adenine)

P P

O O

Summary Section 2.1 All organisms consist of the same kinds of molecules. seemingly small differences in the way those molecules are put together can have big effects inside a living organism.

Section 2.2 Atoms consist of electrons, which carry a negative charge, moving about a nucleus of positively charged protons and uncharged neutrons. The number of protons (the atomic number) determines the element.

Isotopes of an element have the same number of protons but differ in the number of neutrons. The total number of protons and neutrons in the atomic nucleus is called mass number.

Tracers can be made with radioisotopes, which, by radioactive decay, emit particles and energy when their nucleus spontaneously breaks up.

A shell model of an atom represents the energy levels of its electrons as concentric circles. Atoms are in their most stable state when all of their shells are full of electrons, so they tend to get rid of vacancies. Many can do so by gaining or losing electrons, thereby becoming ions. Atoms with unpaired electrons are free radicals. Most free radicals are unstable and dangerous to life.

Section 2.3 A chemical bond unites two atoms in a molecule. A compound is a molecule that consists of two or more elements. An ionic bond is a strong association of two oppositely charged ions. Polarity is a separation of charge into positive and negative

regions. Atoms share a pair of electrons in a covalent bond, which is nonpolar if the sharing is equal, and polar if it is not.

Section 2.4 Two polar covalent bonds give each water molecule an overall polarity. Hydrogen bonds that form among water molecules in tremendous numbers are the basis of water’s unique life-sustaining properties: cohesion, resistance to temperature

changes, and a capacity to act as a solvent for salts and other polar solutes. The amount of solute in a given volume of a solution is the solute’s concentration. Hydrophilic substances dissolve easily in water; hydrophobic substances do not. Evaporation is the transition of a liquid to a vapor.

Section 2.5 pH is a measure of the number of hydrogen ions (H+) in a liquid. At neutral pH (7), there are an equal number of H+ and oH– ions. Acids release hydrogen ions in water; bases accept them. A buffer can keep the pH of solution consistent. Most cell and body fluids are buffered because most molecules of life work only within a narrow range of pH.

Section 2.6 The molecules of life are organic, and chains or rings of carbon atoms form their backbones. All are polymers of sugar, fatty acid, or amino acid

monomers. Enzymes carry out reactions of metabolism.

Section 2.7 cells use carbohydrates for energy, and as structural materials. enzymes assemble polysaccharides such as cellulose from monosaccharide monomers.

Section 2.8 All lipids are nonpolar. A fatty acid is a lipid with an acidic head and a long carbon chain tail. only single bonds link the carbons in the tail of a saturated fatty acid; the tail of an unsaturated fatty acid has one or more double bonds. Fats consist mostly of

triglycerides, which have three fatty acid tails and are nonpolar. When all of a triglyceride’s fatty acid tails are unsaturated, it is called an unsaturated fat; if one or more of the tails is saturated, it is a saturated fat. A lipid bilayer (of phospholipids) is the basic structure of all cell membranes. Waxes are part of water-repellent and lubricating secretions. some steroids function as hormones.

Section 2.9 The shape of a protein is the source of its function. Protein structure begins as a sequence of amino acids linked by peptide bonds into a

polypeptide. Polypeptides twist into loops, sheets, and coils that can pack further into functional domains. Many proteins, including most enzymes, consist of two or more polypeptides. fibrous proteins aggregate into much larger structures. A protein that denatures, or loses its shape, also loses its function. Prion diseases are a fatal consequence of misfolded proteins.

Section 2.10 Nucleotides consist of a five-carbon sugar, a nitrogen-containing base, and one, two or three phosphate groups. Nucleotides are monomers of nucleic acids, and some, especially ATP, have

additional functions. DNA holds heritable information; RNA carries out protein synthesis.

answers in appendix i

1. Which of the following statements is incorrect? a. isotopes have the same atomic number and different mass

numbers. b. Atoms have about the same number of electrons as protons. c. All molecules consist of atoms. d. free radicals are dangerous because they emit energy.

electron

neutron

proton+ +

–

— 14

— 13

— 12

— 11

— 10

— 9

— 8

— 7

— 6

— 5

— 4

— 3

— 2

— 1

— 0

m o

re a

ci d

ic m

o re

b as

cola

beer

corn

milk

battery acid

gastric fluid

acid rain lemon juice

vinegar

orange juice tomatoes, wine bananas

bread black coffee urine, tea, typical rain

butter

pure water

blood, tears egg white seawater

baking soda detergents Tums

toothpaste hand soap milk of magnesia

household ammonia

hair remover

bleach

oven cleaner

drain cleaner

self-Quiz

MOLeCuLeS OF LiFe Chapter 2 43

2. Which element has only one proton?

3. The mutual attraction of opposite charges holds atoms together as molecules in a(n) bond. a. ionic c. polar covalent b. hydrogen d. nonpolar covalent

4. A salt does not release in water. a. ions b. energy c. H+

5. A(n) substance repels water. a. acidic c. hydrophobic b. basic d. polar

6. When dissolved in water, a(n) donates H+ and a(n) accepts H+. a. acid; base c. buffer; solute b. base; acid d. base; buffer

7. is a monosaccharide. a. Glucose c. Ribose e. a and c b. sucrose d. starch f. a, b, and c

8. unlike saturated fatty acids, the tails of unsaturated fatty acids incorporate one or more . a. phosphate groups c. double bonds b. glycerols d. single bonds

9. Which of the following is a class of molecules that encompasses all of the other molecules listed? a. triglycerides c. waxes e. lipids b. fatty acids d. steroids f. phospholipids

10. are to proteins as are to nucleic acids. a. Amino acids; hydrogen bonds c. sugars; lipids b. Amino acids; nucleotides d. sugars; proteins

11. A denatured protein has lost its . a. hydrogen bonds c. function b. shape d. all of the above

12. Match the terms with their most suitable description. hydrophilic a. protons > electrons atomic number b. number of protons in nucleus hydrogen bonds c. polar; dissolves easily in water positive charge d. collectively strong temperature e. protons < electrons negative charge f. measure of molecular motion solution g. solute dissolved in solvent

13. Which of the following are not found in DNA? a. amino acids c. nucleotides b. sugars d. phosphate groups

14. Match the molecules with the best description. wax a. protein primary structure starch b. an energy carrier triglyceride c. water-repellent secretions DNA d. carries heritable information polypeptide e. sugar storage in plants ATP f. richest energy source in animals

15. Match each molecule with its component(s). protein a. glycerol, fatty acids, phosphate phospholipid b. glycerol, three fatty acids triglyceride c. nucleotides nucleic acid d. glucose only cellulose e. sugar, phosphate, base nucleotide f. amino acid monomers wax g. amino acids, sugars glycoprotein h. fatty acids, carbon rings

1. Alchemists were the forerunners of modern-day chemists. Many of these medieval scholars and philosophers spent their lives trying to transform lead (atomic number 82) into gold (atomic number 79). explain why they never succeeded.

2. Draw a shell model of a lithium atom (li), which has 3 protons, then predict whether the majority of lithium atoms on earth are uncharged, positively charged, or negatively charged.

3. Polonium is a rare element with 33 radioisotopes. The most common one, 210Po, has 82 protons and 128 neutrons. When 210Po decays, it emits an alpha particle, which is a helium nucleus (2 protons and 2 neutrons). 210Po decay is tricky to detect because alpha particles do not carry very much energy compared to other forms of radiation. for example, they can be stopped by a single sheet of paper or a few inches of air. That is one reason that authorities failed to discover toxic amounts of 210Po in the body of former KGB agent Alexander litvinenko until after he died suddenly and mysteriously in 2006. What element does an atom of 210Po become after it emits an alpha particle?

4. in the following list, identify the carbohydrate, the fatty acid, the amino acid, and the polypeptide: a. NH2—cHR—cooH c. (methionine)20 b. c6H12o6 d. cH3(cH2)16cooH

critical Thinking

3.1 Food for Thought 46

3.2 What, Exactly, Is a Cell? 46

3.3 Cell Membrane Structure 50

3.4 Introducing Prokaryotic Cells 52

3.5 Introducing Eukaryotic Cells 54

3.6 The Nature of Life 59

C e

ll S

t r

u C

t u

r e

46 Unit 1 HoW CELLS Work

3.1 Food for Thought Cell for cell, microorganisms that live in and on a human body outnumber the person’s own cells by about ten to one. Most are bacteria that live in the digestive tract, but these cells are not just stowaways. Gut bacteria help with digestion, make vitamins that mammals cannot, prevent the growth of dangerous germs, and shape the immune system. One of the most common intestinal bacteria of warm-blooded animals (including humans) is Escherichia coli. Most of the hundreds of types, or strains, of E. coli, are helpful, but a few make a toxic protein that can severely dam- age the lining of the intestine. After ingesting as few as ten cells of a toxic strain, a person may become ill with severe cramps and bloody diarrhea that lasts up to ten days. In some people, complications of infection result in kidney failure, blindness, paralysis, and death. Each year, about 265,000 people in the United States become infected with toxin-producing E. coli.

Strains of E. coli that are toxic to people live in the intestines of other animals — mainly cattle, deer, goats, and sheep—apparently without sickening them. Humans are exposed to the bacteria when they come into contact with animals that harbor them, for example, by eating fresh fruits and vegetables that have contacted animal feces (Figure 3.1). People also become infected with toxic E. coli by eating contami- nated ground meat. An animal’s feces can contaminate its meat during slaughter. Bacteria in the feces stick to the meat, then get thoroughly mixed into it during the grinding process. Unless the contaminated meat is cooked to at least 71°C (160°F), live bacteria will enter the digestive tract of anyone who eats it.

The United States Department of Agriculture (USDA) recalls food products in which toxic bacteria are discovered. Recalled meat is not necessarily discarded; often, it is cooked and processed into ready-to-eat products such as canned chili. Sterilization by cooking or other means kills bacteria, and it is one way to ensure food safety. Raw beef trimmings, which have a high risk of contact with fecal matter during the butchering process, are effectively sterilized when sprayed with ammo- nia. Ground to a paste and formed into pellets or blocks, the resulting product is termed “lean finely textured beef ” or “boneless lean beef trimmings.” This product is routinely used as a filler in prepared food products such as hamburger patties, fresh ground beef, hot dogs, lunch meats, sausages, frozen entrees, canned foods, and other items sold to quick service restaurants, hotel and restaurant chains, institutions, and school lunch programs. In 2012, a series of news reports that nicknamed the product “pink slime” provoked public outrage at its widespread use. Meat industry organizations and the USDA agree that lean finely textured beef, appetizing or not, is perfectly safe to eat because it has been sterilized.

3.2 What, Exactly, Is a Cell? REMEMBER: The cell is the smallest unit with the properties of life (Section 1.2). A tracer is a substance that can be tracked via a detectable component (2.2). Phos- pholipids arranged in a lipid bilayer are the main component of cell membranes (2.8).

The Cell Theory Hundreds of years of observations led to the way we now answer the question, What is a cell? Today we know that a cell carries out metabolism and homeostasis, and reproduces either on its own or as part of a larger organism. By this definition, each cell is alive even if it is part of a multicelled body, and all

Figure 3.1 toxin-producing bacteria can contaminate foods. Top, Escherichia coli cells sticking to the surface of a lettuce leaf. Some strains of this bacteria can cause a serious intestinal illness when they contaminate human food (bottom). Top, © Custom Medical Stock Photo/Getty Images; bottom, Getty Images.

Application

CELL STruCTurE ChaptER 3 47

living organisms consist of one or more cells. We also know that cells reproduce by dividing, so it follows that all existing cells must have arisen by division of other cells (later chapters discuss processes by which cells reproduce). As a cell divides, it passes its hereditary material—its DNA—to offspring. Taken together, these gen- eralizations constitute the cell theory, which is one of the foundations of modern biology (Table 3.1).

Components of All Cells Cells vary in shape and in what they do, but all share certain organizational and functional features: a plasma membrane, cytoplasm, and DNA (Figure 3.2). A cell’s plasma membrane separates it from the external envi- ronment. Like all other cell membranes, it consists mainly of a phospholipid bilayer, and it is selectively permeable, which means that only certain materials can cross it. Thus, a plasma membrane controls exchanges between the cell and its environment. As you will see in Section 3.3, many different proteins embedded in a lipid bilayer or attached to one of its surfaces carry out membrane functions.

The plasma membrane encloses a jellylike mixture of water, sugars, ions, and proteins called cytoplasm. Some or all of a cell’s metabolism occurs in cytoplasm, and the cell’s internal components, including organelles, are suspended in it. Organelles are structures that carry out special metabolic functions inside a cell. Those with membranes compartmentalize substances and activities.

Every cell starts out life with DNA. In nearly all bacteria and archaea, that DNA is suspended directly in cytoplasm. By contrast, the DNA of a eukaryotic cell is contained in a nucleus (plural, nuclei), an organelle with a double membrane. All protists, fungi, plants, and animals are eukaryotes. Some of these organisms are inde- pendent, free-living cells; others consist of many cells working together as a body.

Constraints on Cell Size A living cell must exchange substances with its envi- ronment at a rate that keeps pace with its metabolism. These exchanges occur across the plasma membrane, which can handle only so many exchanges at a time. The rate of exchange across a plasma membrane depends on its surface area: The bigger it is, the more substances can cross it during a given interval. Thus, cell size is limited by a physical relationship called the surface-to-volume ratio. By this ratio, an object’s volume increases with the cube of its diameter, but its surface area increases only with the square.

Apply the surface-to-volume ratio to a round cell. As Figure 3.3 shows, when a cell expands in diameter, its volume increases faster than its surface area does. Imagine that our round cell expands until it is four times its original diameter. The volume of the cell has increased 64 times (43), but its surface area has increased only 16 times (42 ). Each unit of plasma membrane must now handle exchanges for four times as much cytoplasm (64 ÷ 16 = 4). If the cell gets too big, the inward flow of nutrients and the outward flow of wastes across that membrane will not be fast enough to keep the cell alive.

Figure 3.2 General organization of a cell. All cells start out life with a plasma membrane, cyto- plasm, and DNA. This one is a cell from a plant.

plasma membrane

cytoplasm

DNA in nucleus

1. Each organism consists of one or more cells.

2. The cell is the structural and functional unit of all organisms. A cell is the smallest unit of life, individually alive even as part of a multicelled organism.

3. All living cells arise by division of preexisting cells.

4. Cells contain hereditary material (DNA), which they pass to their offspring when they divide.

table 3.1 the Cell theory

Figure 3.3 Examples of surface-to-volume ratio. This physical relation- ship between increases in volume and surface area limits the size and influ- ences the shape of cells.

Diameter (cm) 2 3 6

Surface area (cm2) 12.6 28.2 113

Volume (cm3) 4.2 14.1 113

Surface-to-volume ratio 3:1 2:1 1:1

cell theory Theory that all organisms consist of one or more cells, which are the basic unit of life; all cells come from division of preexisting cells; and all cells pass DNA to offspring.

cytoplasm Semifluid substance enclosed by a cell’s plasma membrane.

nucleus of a cell, an organelle with two membranes that holds the cell’s DNA.

organelle Structure that carries out a special meta- bolic function inside a cell.

plasma membrane Membrane that encloses a cell and separates it from the external environment.

surface-to-volume ratio A relationship in which the volume of an object increases with the cube of the diameter, and the surface area increases with the square.

48 Unit 1 HoW CELLS Work

Surface-to-volume limits also affect the form of colonial organisms such as strandlike algae, in which small cells attach end to end so each one can interact directly with the environment. It also affects the form of cells in multicelled bodies. For example, some types of muscle cells in your thighs run the length of your upper leg. Each of these cells is thin, so it exchanges substances efficiently with fluids in the surrounding tissue.

How Do We See Cells? No one even knew cells existed until well after the first microscopes were invented. This is because typical cells are in the micrometer range of size—much smaller than the unaided human eye can perceive (Figure 3.4). One micrometer (µm) is one-thousandth of a millimeter, which is one-thousandth of a meter (Table 3.2). In a light microscope, visible light illuminates a sample. As you will learn in Chapter 5, all light travels in waves. This property of light causes it to bend when passing through a curved glass lens. Inside a light microscope, such lenses focus light that passes through a specimen, or bounces off of one, into a mag- nified image (Figure 3.5A). Microscopes that use polarized light can yield images in which the edges of some structures appear in three-dimensional relief (Figure 3.5B). Photographs of images enlarged with a microscope are called micrographs; those taken with visible light are called light micrographs (LM).

Most cells are nearly transparent, so their internal details may not be visible unless they are first stained, or exposed to dyes that only some cell parts soak up. Parts that absorb the most dye appear darkest. Staining results in an increase in con- trast (the difference between light and dark) that allows us to see a greater range of detail. Researchers often use light-emitting tracers to pinpoint the location of a mol- ecule of interest within a cell. When illuminated with a laser, these tracers fluoresce (emit light), and an image of the emitted light can be captured with a fluorescence microscope (Figure 3.5C). Such images are called fluorescence micrographs.

Structures smaller than about 200 nanometers across appear blurry under light microscopes. To observe objects of this size range clearly, we would have to switch to an electron microscope. There are two types of electron microscope; both use magnetic fields as lenses to focus a beam of electrons onto a sample. A transmission electron microscope directs electrons through a thin specimen, and the specimen’s internal details appear as shadows in the resulting image, which is called a transmis- sion electron micrograph, or TEM (Figure 3.5D). A scanning electron microscope directs a beam of electrons back and forth across the surface of a specimen that has been coated with a thin layer of gold or other metal. The irradiated metal emits

Figure 3.4 Relative sizes. Below, the diameter of most cells is between 1 and 100 micrometers. Table 3.2 shows conversions among units of length; also see units of Measure, Appendix IV. Louse, Edward S. Ross; Ant, Vladimir Davydov/iStock/360/Getty Images; Frog, © A Cotton Photo/Shutterstock; Rat, © Pakhnyushcha/Shutterstock; Goose, panbazil/Shutterstock.com; Boy, © Piotr Marcinski/Shutterstock; Giraffe, © Valerie Kalyuznnyy/Photos.com; Whale, Dorling Kindersley/Getty Images.

table 3.2 Common Units of Length

Unit Equivalent

Meter inch

centimeter (cm) 1/100 0.394

millimeter (mm) 1/1000 0.0394

micrometer (μm) 1/1,000,000 0.0000394

nanometer (nm) 1/1,000,000,000 0.0000000394

meter (m) 100 cm 1,000 mm 1,000,000 µm 1,000,000,000 nm

39.4

electron microscopes light microscopes

human eye (no microscope)

molecules of life viruses mitochondria, chloroplasts

most bacteria

most eukaryotic

cells small animals largest organisms

small molecules

lipids carbohydrates DNA proteins frog eggs

0.1 nm 1 nm 10 nm 100 nm 1 µm 10 µm 100 µm 1 mm 1 cm 10 cm 1 m 10 m 100 m

electron microscopes light microscopes

human eye (no microscope)

molecules of life viruses mitochondria, chloroplasts

most bacteria

most eukaryotic

cells small animals largest organisms

small molecules

lipids carbohydrates DNA proteins frog eggs

0.1 nm 1 nm 10 nm 100 nm 1 µm 10 µm 100 µm 1 mm 1 cm 10 cm 1 m 10 m 100 m

CELL STruCTurE ChaptER 3 49

electrons and x-rays, which are converted into an image (a scanning electron micro- graph, or SEM) of the surface (Figure 3.5E). SEMs and TEMs are always black and white; colored versions have been digitally altered to highlight specific details.

Take-Home Message 3.2 how are all cells alike?

• All cells start life with a plasma membrane, cytoplasm, and a region of DNA. In eukaryotic cells only, the DNA is contained within a nucleus.

• The surface-to-volume ratio limits cell size and influences cell shape. • Different types of microscopes reveal different aspects of cell structure.

electron microscopes light microscopes

human eye (no microscope)

molecules of life viruses mitochondria, chloroplasts

most bacteria

most eukaryotic

cells small animals largest organisms

small molecules

lipids carbohydrates DNA proteins frog eggs

0.1 nm 1 nm 10 nm 100 nm 1 µm 10 µm 100 µm 1 mm 1 cm 10 cm 1 m 10 m 100 m

electron microscopes light microscopes

human eye (no microscope)

molecules of life viruses mitochondria, chloroplasts

most bacteria

most eukaryotic

cells small animals largest organisms

small molecules

lipids carbohydrates DNA proteins frog eggs

0.1 nm 1 nm 10 nm 100 nm 1 µm 10 µm 100 µm 1 mm 1 cm 10 cm 1 m 10 m 100 m

E. A scanning electron micrograph (SEM) shows details of the cell’s surface, including its thick coat of cilia. The indentation (also visible in a) is where the cell takes in food.

D. A colorized transmis- sion electron micrograph (TEM) reveals several types of internal structures in a plane (slice). Ingested algae are being broken down inside food vacuoles.

C. In this fluorescence micrograph, yellow pinpoints the location of a particular protein in the membrane of organelles called contractile vacuoles. These organelles are also visible in B.

B. A light micrograph taken with polarized light shows edges in relief. This technique reveals ingested algae, and also some inter- nal structures that are not visible in a.

a. Green blobs visible in this light micrograph (LM) of a living cell are ingested algae. Hairlike structures on the cell’s surface are waving cilia that propel this motile organism through fluid surroundings.

50 µm

Figure 3.5 Different microscopes reveal different characteristics of the same organism, a single-celled protist called Paramecium. (A) Nancy Nehring/iStockphoto.com; (B) Michael Abbey/Science Source; (C) © Dennis Kunkel Microscopy, Inc./PhototakeUSA.com; (D) © Microworks/PhototakeUSA.com; (E) Steve Gschmeissner/Science Source.

50 Unit 1 HoW CELLS Work

A cell’s basic structure is essentially a lipid bilayer bubble filled with fluid.

extracellular fluid

cytoplasmlipid bilayer

one layer of lipids

Figure 3.6 Cell membrane structure. organization of phospholipids in cell membranes (a) and examples of com- mon membrane proteins (B–E). For clarity, these proteins are often modeled as blobs or geometric shapes; their structure can be extremely complex.

a. In a watery fluid, phospholipids spontaneously line up into two layers: the hydrophobic tails cluster together, and the hydrophilic heads face outward, toward the fluid. This lipid bilayer forms the framework of all cell membranes. Many types of proteins intermingle among the lipids; a few that are typical of plasma membranes are shown opposite.

3.3 Cell Membrane Structure REMEMBER: Phospholipids have a phosphate-containing head and two fatty acid tails; the tails can vary in length and in saturation (Section 2.8).

The foundation of all cell membranes is a lipid bilayer that consists mainly of phospholipids (Figure 3.6A). The head of a phospholipid is highly polar and hydro-

philic, which means that it interacts with water molecules. Its two long hydrocarbon tails are very nonpolar and hydrophobic, so they do not

interact with water molecules. As a result of these opposing proper- ties, phospholipids swirled into water will spontaneously organize themselves into lipid bilayer sheets or bubbles, with hydrophobic tails together, hydrophilic heads facing the watery surroundings. A

cell’s basic structure is essentially a lipid bilayer bubble filled with fluid (left).

Other molecules, including cholesterol, proteins, glycoproteins, and glycolipids, are embedded in or attached to the lipid bilayer of a cell membrane. Many of these molecules can move around the membrane more or less freely. We use the term fluid mosaic to describe a membrane of a eukaryotic or bacterial cell because it behaves like a two-dimensional liquid of mixed composition. Membrane fluidity occurs because phospholipids in the bilayer are not chemically bonded to one another; they stay organized as a result of collective hydrophobic and hydro- philic attractions. These interactions are, on an individual basis, relatively weak. Thus, individual phospholipids in the bilayer drift sideways and spin around their long axis, and their tails wiggle.

A cell membrane’s properties vary depending on the types and proportions of molecules composing it. For example, membrane fluidity decreases with increasing cholesterol content. A membrane’s fluidity also depends on the length and satura- tion of its phospholipids’ fatty acid tails. Archaea do not even use fatty acids to build their phospholipids. Instead, they use molecules with reactive side chains, so the tails of archaeal phospholipids form covalent bonds with one another. As a result of this rigid crosslinking, archaeal phospholipids do not drift, spin, or wiggle in a

fluid

CELL STruCTurE ChaptER 3 51

adhesion protein Plasma membrane protein that fastens cells together in animal tissues.

fluid mosaic Model of a cell membrane as a two- dimensional fluid of mixed composition.

receptor protein Membrane protein that triggers a change in cell activity in response to a stimulus such as binding a certain substance.

transport protein Protein that moves specific ions or molecules across a membrane.

extracellular fluid

cytoplasmlipid bilayer

one layer of lipids

B. adhesion proteins fasten cells together or to external proteins. This one connects protein fila- ments inside the cell with external filaments in animal tissues.

D. Enzymes speed reactions at membranes. This one is part of a membrane-bound set of mol- ecules that together break down drugs and other organic toxins.

E. transport proteins bind to mole cules on one side of the membrane, and release them on the other side. This one transports glucose.

C. Receptor proteins trigger a change in cellular activity in response to a stimulus such as binding to a particular substance. This one occurs on cells of the immune system.

bilayer. Thus, membranes of archaea are stiffer than those of bacteria or eukaryotes, a characteristic that may help these cells survive in extreme habitats.

Membrane Proteins A cell membrane physically separates an external environ- ment from an internal one, but that is not its only task. Many types of proteins are associated with a cell membrane, and each type adds a specific function to it. Thus, different cell membranes can carry out different tasks depending on which proteins are associated with them. A plasma membrane incorporates certain proteins that no internal cell membrane has, so it has functions that no other membrane does. For example, cells stay organized in animal tissues because adhesion proteins in their plasma membranes fasten them together and hold them in place (Figure 3.6B). Plasma membranes and some internal membranes incorporate receptor proteins, which trigger a change in the cell’s activities in response to a stimulus (Figure 3.6C). Each type of receptor protein receives a particular stimulus, such as binding to a certain hormone. Each receptor protein also triggers a specific response inside the cell, which may involve metabolism, movement, division, or even cell death.

All cell membranes incorporate enzymes (Figure 3.6D). Some membrane enzymes act on other proteins or lipids that are part of the lipid bilayer. All mem- branes also have transport proteins, which move specific substances across the bilayer (Figure 3.6E). These proteins are important because lipid bilayers are imper- meable to ions and polar molecules (we return to this topic in Section 4.5).

Take-Home Message 3.3 What is a cell membrane?

• The foundation of all cell membranes is the lipid bilayer: two layers of phospho lipids, tails sandwiched between heads.

• Proteins that associate with lipid bilayers add various functions to a membrane.

52 Unit 1 HoW CELLS Work

pilus

DNA in nucleoid

flagellum

cell wall

plasma membrane

capsule

cytoplasm, with ribosomes

Figure 3.8 Generalized body plan of a prokaryote.

3.4 Introducing Prokaryotic Cells REMEMBER: A polysaccharide is a long chain of monosaccharides (Section 2.7); a peptide is a short chain of amino acids (2.9).

All bacteria and archaea are single-celled organisms, although individual cells of many species cluster in filaments or colonies (Figure 3.7). Outwardly, cells of the two groups appear so similar that archaea were once presumed to be an unusual group of bacteria. Both were classified as prokaryotes, a word that means “before the nucleus.” By 1977, it had become clear that archaea are more closely related to eukaryotes than to bacteria, so they were given their own separate domain. The term “prokaryote” is now an informal designation only.

Bacteria and archaea are the smallest and most metabolically diverse forms of life that we know about. Chapter 13 revisits them in more detail; here we present an overview of structures shared by both groups (Figure 3.8).

Compared with eukaryotic cells, prokaryotes have little in the way of internal framework, but they do have protein filaments under the plasma membrane that reinforce the cell’s shape and act as scaffolding for internal structures. The cytoplasm of these cells

contains many ribosomes (organelles upon which polypeptides are assembled), and in some species, additional organelles. The cytoplasm also contains plasmids, which are small circles of DNA that carry a few genes (units of inheritance). The cell’s remaining genes typically occur on one large circular molecule of DNA located in an irregularly shaped region of cytoplasm called the nucleoid

. In a few species, the nucleoid is enclosed by a membrane. Other internal membranes carry out special metabolic processes such as photosynthesis (Figure 3.7B).

Like all cells, bacteria and archaea have a plasma membrane 3

. In nearly all prokaryotes, a rigid cell wall

surrounding the plasma membrane protects the cell and supports its shape. Archaeal cell walls and bacterial cell walls differ, but both types are permeable to water, so dissolved substances easily cross. Many spe- cies of bacteria, including the ones shown in Figure 3.7, have a second membrane

B. Oscillatoria are a type of cyanobacteria, an ancient lineage of photosynthetic bacteria. Photosynthesis occurs at internal membranes (green). The multi- sided structures (pink) are protein-enclosed organ- elles called carboxysomes that assist photosynthesis.

a. Escherichia coli is a common bacterial inhabit- ant of human intestines. Short, hairlike structures are pili; longer ones are flagella. This one is harm- less; others can cause disease in humans.

C. Ferroglobus placidus is an archaeon that thrives in superheated water spewing from the ocean floor. The durable composition of its lipid bilayers (note the gridlike texture) keeps them intact at extreme heat and pH.

1 µm0.5 µm 0.5 µm

Figure 3.7 Some representative prokaryotes. (A, B) © Biophoto Associates/Science Source; (C) © K.O. Stetter & R. Rachel, Univ. Regensburg; (D) Cryo-EM image of Haloquadratum walsbyi, isolated from Australia. Courtesy of Zhuo Li (City of Hope, Duarte, California, USA), Mike L. Dyall-Smith (Charles Sturt University, Australia), and Grant J. Jensem (California Institute of Technology, Pasadena, California, USA); (E) Biomedical Imaging Unit, Southhampton General Hospital/Science Photo Library; (F) Archivo Angels Tapias y Fabrice Confalonieri.

CELL STruCTurE ChaptER 3 53

biofilm Community of microorganisms living within a shared mass of slime.

cell wall Semirigid but permeable structure that sur- rounds the plasma membrane of some cells.

flagellum Long, slender cellular structure used for movement.

pilus A protein filament that projects from the sur- face of some prokaryotic cells.

ribosome organelle of protein synthesis.

around the cell wall. Outside the cell wall (or the second membrane) is a thick, gelatinous capsule

and/or a loosely attached layer of slime. Protein filaments called pili (singular, pilus)

project from the wall of some prokaryotes. Pili help these cells move across or cling to surfaces. One kind, a “sex” pilus, attaches to another bacterium and then shortens. The attached cell is reeled in, and DNA is transferred from one cell to the other. Many types of bacteria and archaea also have one or more flagella projecting from their surface

. Flagella (singular, flagellum) are long, slender cellular structures used for motion. A pro- karyotic flagellum rotates like a propeller that drives the cell through fluid habitats.

Biofilms Bacterial cells often live so close together that an entire community shares a layer of slime. A communal living arrangement in which single-celled organisms occupy a shared mass of slime is called a biofilm. A biofilm is often attached to a solid surface, and may include bacteria, algae, fungi, protists, and/or archaea. Participating in a biofilm allows the cells to linger in a favorable spot rather than be swept away by fluid currents, and to reap the benefits of living communally. For example, rigid or netlike secretions of some species serve as permanent scaffold- ing for others; species that break down toxic chemicals allow more sensitive ones to thrive in habitats that they could not withstand on their own; and waste products of some serve as raw materials for others. Later chapters discuss some medical implica- tions of biofilms, including dental plaque (Figure 3.9).

Take-Home Message 3.4 how are bacteria and archaea alike?

• Bacteria and archaea do not have a nucleus. Most kinds have a cell wall around their plasma membrane. The permeable wall reinforces and imparts shape to the cell body.

• The structure of bacteria and archaea is relatively simple, but as a group these organ- isms are the most diverse forms of life.

D. The square archaeon Haloquadratum walsbyi prefers brine pools saltier than soy sauce. Gas-filled organelles (white structures) buoy these highly motile cells, which can aggregate into flat sheets a bit like floor tiles.

F. The archaeonThermococcus gammatolerans lives under extreme conditions of salt, temperature, and pressure. It is by far the most radiation-resistant organism ever discovered, capable of withstanding thousands of times more radiation than humans can.

0.5 µm0.5 µm

E. Helicobacter pylori, a bacterium that can cause stomach ulcers when it infects the lining of the stomach, takes on a ball-shaped form (shown) that offers protection from environmen- tal challenges such as antibiotic treatment.

0.5 µm 0.5 µm

Figure 3.9 Oral bacteria in dental plaque, a biofilm. This micrograph shows two species of bacteria (tan, green) and a yeast (red) sticking to one another and to teeth via a gluelike mass of shared, secreted polysaccha- rides (pink). other secretions of these organisms cause cavities and periodontal disease. © Dennis Kinkel Microscopy, Inc./Phototake.

54 Unit 1 HoW CELLS Work

Figure 3.10 Common components of eukaryotic cells. An animal cell is illustrated here.

The nucleus protects and controls access to the cell’s DNA.

Vesicles form by budding from other components of the endomembrane system or from the plasma membrane. Some transport substances among organelles of the Er, and to and from the plasma membrane. others store or break down substances.

ribosomes attached to rough endoplasmic reticulum (Er) assemble polypeptides that thread into the Er’s interior, where they take on tertiary structure and assemble with other polypeptides.

Many proteins made in rough Er migrate through the Er compartment to smooth Er. Some of these proteins stay in smooth Er, as enzymes that assemble lipids and break down carbohydrates, wastes, and toxins. others are packaged in vesicles for transport to Golgi bodies.

Golgi bodies modify proteins and lipids, then sort and repackage the finished molecules into new ves- icles. Some of the new vesicles become lysosomes. others carry proteins to the plasma membrane for insertion into the lipid bilayer or secretion.

Mitochondria specialize in efficient production of ATP.

3.5 Introducing Eukaryotic Cells REMEMBER: Hydrogen bonding makes the loops, helices, and sheets of a polypep- tide fold up into functional domains; many proteins consist of two or more polypep- tides; fibrous proteins aggregate by many thousands into much larger structures (Section 2.9). ATP has an important metabolic role as an energy carrier (2.10).

In addition to a nucleus, a typical eukaryotic cell has many other membrane-enclosed organelles (Figure 3.10). An enclosing membrane allows an organelle to regulate the types and amounts of sub- stances that enter and exit. Through this control, the organelle maintains a special internal environment that allows it to carry out a particular function—for example, isolating toxic or sensitive substances from the rest of the cell, moving substances through cytoplasm, maintaining fluid balance, or providing a favorable environment for a special process.

The Nucleus A cell nucleus serves two important functions. First, it keeps the cell’s genetic mate- rial—its one and only copy of DNA—away from metabolic processes that might damage it. Isolated in its own compartment, the DNA stays separated from the bustling activity of the cytoplasm

. Second, a nucleus controls the passage of certain

molecules across its membrane. The nucleus has a special membrane, the nuclear envelope, that carries out this function. A nuclear envelope consists of two lipid bilayers folded together. Proteins embedded in the two lipid bilayers aggregate into thousands of tiny nuclear pores that span the envelope (Figure 3.11). Some bacteria have membranes around their DNA, but we do not consider the bacteria to have nuclei because there are no pores in these membranes.

Large molecules, including RNA and proteins, cannot cross lipid bilayers on their own. Nuclear pores function as gateways for these molecules to enter and exit a nucleus. Protein synthesis offers an example of why this movement is important. Protein synthesis occurs in cytoplasm, and it requires the participation of many molecules of RNA. RNA is produced in the nucleus. Thus, RNA molecules must move from nucleus to cytoplasm, and they do so through nuclear pores. Proteins that carry out RNA synthesis must move in the opposite direction, because this process occurs in the nucleus.

The Endomembrane System The endomembrane system is a series of interact- ing organelles between the nucleus and the plasma membrane. Its main function is to make lipids, enzymes, and proteins for insertion into the cell’s membranes or secretion to the external environment. The endomembrane system also destroys toxins, recycles wastes, and has other special functions. Components of the system vary among different types of cells, but here we present an overview of the most common ones.

Small, membrane-enclosed sacs called vesicles 2

form by budding from other organelles or when a patch of plasma membrane sinks into the cytoplasm. Many types carry substances from one organelle to another, or to and from the

CELL STruCTurE ChaptER 3 55

0.5 µm

plasma membrane. Some are a bit like trash cans that collect and dispose of waste, debris, or toxins. Enzymes in vesicles called peroxisomes break down fatty acids, amino acids, and poisons such as alcohol. They also break down hydrogen peroxide, a toxic by-product of fatty acid breakdown. Even more powerful enzymes in vesicles called lysosomes break down cellular debris and wastes. Ingested bacteria, cell parts, and other particles are delivered to lysosomes for breakdown.

Vacuoles are sacs that form by the fusion of multiple vesicles. Many isolate or break down waste, debris, toxins, or food. Plant cells have a large central vacuole that collects amino acids, sugars, ions, wastes, and toxins. Fluid pressure in a central vacuole keeps plant cells plump, so stems, leaves, and other plant parts stay firm (a central vacuole is illustrated to the left of the nucleus in Figure 3.2).

Endoplasmic reticulum (ER) is a system of tubes and flattened sacs. The membrane of the ER extends from the nuclear envelope, and it encloses a single, continuous compartment. Two kinds of ER, rough and smooth, are named for their appearance in electron micrographs. Thousands of ribosomes attached to the outer surface of rough ER give this organelle its “rough” appearance

. These ribosomes make polypeptides that thread into the interior of the ER as they are assembled. Inside the ER, the polypeptides take on their tertiary structure, and many assemble with other polypeptides. Cells that make, store, and secrete proteins have a lot of rough ER.

Some proteins made in rough ER become part of its membrane. Others migrate through the ER compartment to smooth ER. Smooth ER has no ribosomes, so it does not make its own proteins

. Some proteins that arrive in smooth ER are immediately packaged into vesicles for delivery elsewhere. Others are enzymes that stay and become part of the smooth ER. Enzymes of the smooth ER make lipids for the cell’s membranes, and they break down carbohydrates, fatty acids, and some drugs and poisons.

A Golgi body has a folded membrane that often looks like a stack of pancakes

. Enzymes inside of Golgi bodies put finishing touches on proteins and lipids that have been delivered from ER. The finished products are sorted and packaged in new vesicles. Some of the vesicles deliver their cargo to the plasma membrane; others become lysosomes.

Mitochondria The mitochondrion (plural, mitochondria) 6

is a eukaryotic organelle that specializes in making ATP by aerobic respiration (Chapter 5 details this metabolic pathway). A mitochondrion has two membranes, one highly folded inside the other (Figure 3.12), that form its ATP-making machinery. The organelle

Figure 3.11 the nucleus. This organelle is the defining characteristic of eukaryotic cells. TEM shows a liver cell nucleus. © Kenneth Bart.

endoplasmic reticulum (ER) Membrane-enclosed organelle that is a continuous system of sacs and tubes extending from the nuclear envelope. Smooth Er makes lipids and breaks down carbohydrates and fatty acids; ribosomes on the surface of rough Er make polypeptides.

Golgi body organelle that modifies polypeptides and lipids, then packages the finished products into vesicles.

lysosome Enzyme-filled vesicle that breaks down cellular wastes and debris.

mitochondrion Eukaryotic organelle that produces ATP by aerobic respiration.

nuclear envelope A double membrane that con- stitutes the outer boundary of the nucleus. Nuclear pores in the membrane control the entry and exit of large molecules.

peroxisome Enzyme-filled vesicle that breaks down amino acids, fatty acids, and toxic substances.

vesicle Small, membrane-enclosed organelle; dif- ferent kinds store, transport, or break down their contents.

Figure it Out: What organelle is visible to the upper right in the micrograph? answer: rough Er

1 µm

DNA

nuclear envelope

nuclear pore

Figure 3.12 the mitochondrion. Two membranes, one folded inside the other, form the ATP-making machinery of this eukaryotic organelle. The TEM shows a mitochondrion in a cell from bat pancreas. Keith R. Porter.

outer membrane

outer compartment

inner compartment

inner membrane

56 Unit 1 HoW CELLS Work

Organelles and Cystic Fibrosis

A plasma membrane transport protein called CFTr moves chloride ions out of cells lin- ing cavities and ducts of the lungs, liver, pancreas, intestines, and reproductive system. Water that follows the ions creates a thin film that allows mucus to slide easily through these structures.

People with cystic fibrosis (CF) have too few copies of the CFTr protein in the plasma membranes of their cells. Not enough chloride ions leave the cells, and so not enough water leaves them either. The result is thick, dry mucus that clogs the airways to the lungs and other passages. Symptoms include difficulty breathing and chronic lung infections. In 2000, researchers tracked the cellular location of the CFTr protein as it was being produced in cells from people with CF (Figure 3.13).

1. Which organelle contains the least amount of CFTr protein in normal cells? In CF cells?

2. In which organelle is the amount of CFTr protein most similar in both types of cells? 3. Where is the CFTr protein getting held up in cells of people who have CF?

Figure 3.13 Cellular location of the CFtR protein. Graph compares the amounts of CFTr protein found in endo- plasmic reticulum, vesicles traveling from Er to Golgi, and Golgi bodies in CF cells and normal cells.

Digging Into Data

resembles a bacterium in size, form, and biochemistry. Mitochondria have their own DNA, which is circular and otherwise similar to bacterial DNA. They divide independently of the cell, and have their own ribosomes. Such clues led to a theory that mitochondria evolved from aerobic bacteria that took up permanent residence inside a host cell (we return to this topic in Section 13.3).

Chloroplasts Photosynthetic cells of plants and many protists have chloroplasts, which are organelles specialized for photosynthesis. Most chloroplasts are oval or disk-shaped (Figure 3.14). Each has two outer membranes enclosing a semifluid interior, the stroma, that contains enzymes and the chloroplast’s own DNA. In the stroma, a third, highly folded membrane forms a single, continuous compartment. Photosynthesis occurs at this inner membrane. In many ways, chloroplasts resemble the photosynthetic bacteria from which they evolved.

The Cytoskeleton Between the nucleus and plasma membrane of all eukaryotic cells is a system of protein filaments collectively called the cytoskeleton. Elements of the cytoskeleton reinforce, organize, and move cell structures, and often the whole cell. Some are permanent; others form only at certain times.

Microtubules are long, hollow cylinders that consist of subunits of the protein tubulin (Figure 3.15A). They form a dynamic scaffolding for many cellular pro- cesses, rapidly assembling when they are needed, disassembling when they are not. For example, before a eukaryotic cell divides, microtubules assemble, separate the cell’s duplicated DNA molecules, then disassemble. As another example, microtu- bules that form in the growing end of a young nerve cell support its lengthening in a particular direction (Figure 3.15C).

Figure 3.14 the chloroplast. Each chloroplast has two outer membranes. Photosyn- thesis occurs at a third, much-folded inner membrane. TEM shows a chloroplast from a cell in a corn leaf. Science Source.

two outer membranes

stroma

inner membrane

1 µm

normal cells

Am ou

nt o

f C FT

r p

ro te

CF cells

Er vesicles Golgi

CELL STruCTurE ChaptER 3 57

Microfilaments are fine fibers that consist primarily of subunits of a protein called actin (Figure 3.15B). These fibers strengthen or change the shape of eukaryotic cells, and have a critical function in cell migration, movement, and contraction. Crosslinked, bundled, or gel- like arrays of them make up the cell cortex, a reinforcing mesh under the plasma membrane. Microfilaments also connect plasma mem- brane proteins to other proteins inside the cell.

Intermediate filaments are the most stable elements of the cytoskeleton, forming a framework that lends structure and resilience to cells and tissues in multicelled organ- isms. Several types of intermediate filaments are assembled from different proteins. For example, intermediate filaments that make up your hair consist of keratin, a fibrous protein. Intermediate filaments of lamins (another fibrous protein) support the nuclear envelope, and also help regulate processes inside the nucleus such as DNA replication.

Motor proteins that associate with cytoskeletal elements move cell parts when energized by a phosphate-group transfer from ATP. A cell is like a bustling train sta- tion, with molecules and structures being moved continuously throughout its inte- rior. Motor proteins are a bit like freight trains, dragging cellular cargo along tracks of microtubules and microfilaments (Figure 3.16). One motor protein, myosin, brings about muscle cell contraction by interacting with microfilaments. Dynein, another motor protein, interacts with microtubules to bring about move- ment of eukaryotic flagella and cilia. Eukaryotic flagella propel sperm and other motile cells through fluid by whipping back and forth, a motion that differs from the propeller-like rotation of prokaryotic flagella. Cilia (singular, cilium) are short, hairlike structures that project from the surface of some eukaryotic cells. The coordinated waving of many cilia can propel a cell through fluid, and stir fluid around a stationary cell. Cilia on thousands of cells lining your airways sweep inhaled particles away from your lungs.

Some eukaryotic cells, including the amoeba at left, form pseudopods, or “false feet.” As these temporary, irregular lobes bulge outward, they can move the entire cell or engulf a target such as prey. Elongating microfilaments force the lobe to advance in a steady direction. Motor proteins attached to the microfilaments drag the plasma membrane along with them.Ast

rid H

an ns

-F rie

de rM

ic hl

er /

Sc ie

nc e

So ur

chloroplast organelle of photosynthesis in the cells of plants and photosynthetic protists.

cilia Short, movable structures that project from the plasma membrane of some eukaryotic cells.

cytoskeleton Network of protein filaments that sup- port, organize, and move eukaryotic cells and their internal structures.

intermediate filament Stable cytoskeletal element that structurally supports cells and tissues.

microfilament reinforcing cytoskeletal element that functions in cell movement; a fiber of actin subunits.

microtubule Cytoskeletal element involved in move- ment; hollow filament of tubulin subunits.

motor protein Type of energy-using protein that interacts with cytoskeletal elements to move the cell’s parts or the whole cell.

pseudopod A temporary protrusion that helps some eukaryotic cells move and engulf prey.

a. Microtubule. B. Microfilament.

C. A fluorescence micrograph shows microtubules (yel- low) and microfilaments (blue) in the growing end of a nerve cell. These cytoskeletal elements support and guide the cell’s lengthening in a particular direction.

Figure 3.15 Cytoskeletal elements. (C) © Dylan T. Burnette and Paul Forscher.

actin subunit

tubulin subunit

25 nm 6–7 nm

10 µm

Figure 3.16 Motor proteins. Here, kinesin (tan) drags a pink vesicle as it inches along a microtubule.

58 Unit 1 HoW CELLS Work

cuticle

outer cell of leaf

photosynthetic cell inside leaf

Figure 3.17 a plant ECM. This section through a plant leaf shows the cuticle, a protective covering of deposits secreted by living cells. George S. Ellmore.

Extracellular Matrix Many cells secrete an extracellular matrix (ECM), a com- plex mixture of molecules that varies by cell type, but often includes polysaccharides and fibrous proteins. A cell wall is an example of ECM. You learned in Section 3.4 that many prokaryotes have walls. Plants have them too, as do fungi and some protists. Wall composition differs among these groups. Animal cells have no walls, but some types secrete an extracellular matrix called basement membrane. Despite the name, basement membrane is not a cell membrane because it does not con- sist of lipids. Rather, it is a sheet of fibrous material that structurally supports and organizes tissues. A cuticle is a type of ECM secreted by cells at a body surface. In plants, a cuticle of waxes and other hydrophobic compounds helps stems and leaves fend off insects and retain water (Figure 3.17). Crabs, spiders, and other arthropods have a cuticle that consists mainly of chitin, a tough polysaccharide.

Cell Junctions In multicelled species, cells can interact with one another and their surroundings by way of cell junctions. Cell junctions are structures that connect a cell directly to other cells or to its environment. Cells send and receive substances and signals through some junctions. Other junctions help cells recognize and stick to each other and to ECM.

Three types of cell junctions are common in animal tissues (Figure 3.18). In tissues that line body surfaces and internal cavities, rows of tight junctions fasten the plasma membranes of adjacent cells and prevent body fluids from seeping between them. For example, the lining of the stomach is leakproof because tight junctions seal its cells together. Adhering junctions consist of adhesion proteins, and they make a tissue quite strong by connecting cytoskeletal elements of adjacent cells, and cytoskeletal elements to basement membrane. Contractile tissues (such as heart muscle) have a lot of adhering junctions, as do tissues subject to abrasion or stretch- ing (such as skin). Gap junctions are closable channels that connect the cytoplasm of adjoining animal cells. When open, they permit water, ions, and small molecules to pass directly from the cytoplasm of one cell to another. These channels allow entire regions of cells to respond to a single stimulus. Heart muscle and other tissues in which the cells perform a coordinated action have many gap junctions.

In plants, plasmodesmata (singular, plasmo desma) are open channels that connect the cytoplasm of adjoining cells. These cell junctions extend across the cell walls, and, like gap junctions, they allow substances to flow quickly from cell to cell.

Take-Home Message 3.5 What structures are common in eukaryotic cells?

• A typical eukaryotic cell has many membrane-enclosed organelles. • A nucleus protects and controls access to the cell’s DNA. organelles of the endomem-

brane system make, modify, and transport proteins and lipids. Mitochondria produce ATP; chloroplasts carry out photosynthesis.

• An extensive cytoskeleton of protein filaments reinforces a eukaryotic cell’s shape, and is the basis of movement of the cell and its parts.

• Many cells secrete an extracellular matrix (ECM) such as a cell wall. Plant cells, fungi, and some protists are walled, but not animal cells.

• Cell junctions structurally and functionally connect cells in tissues. In animal tissues, cell junctions also connect cells with basement membrane.

Figure 3.18 three types of cell junctions common in animal tissues: tight junctions, gap junctions, and adhering junctions. The micrograph shows how a profusion of tight junctions (green) seals abutting surfaces of kidney cell membranes to form a waterproof tissue. The DNA in each cell nucleus appears red. © ADVANCELL (Advanced In Vitro Cell Technologies; S.L.) www.advancell.com.

adhering junctions

gap junctions

basement membrane

tight junctions

free surface of epithelial tissue

CELL STruCTurE ChaptER 3 59

cell junction Structure that connects a cell to another cell or to extracellular matrix.

cuticle Secreted covering at a body surface.

extracellular matrix (ECM) Complex mixture of cell secretions, the composition and function of which vary by cell type.

Kevin Schafer/Getty Images.

3.6 The Nature of Life Carbon, hydrogen, oxygen, and other atoms of organic molecules are the stuff of you, and us, and all of life. Yet it takes more than organic molecules to complete the picture. Life continues only as long as an ongoing flow of energy sustains its organization, because assembling molecules and cells requires energy. Life is no more and no less than a marvelously complex system for prolonging order. With energy and the heredi- tary codes of DNA, matter becomes organized, generation after generation.

In this chapter, you learned about the structure of cells, which have at mini- mum a plasma membrane, cytoplasm, and DNA. We often use differences in other cellular components—the presence or absence of a particular organelle, for example—to categorize life’s diversity. What about life’s commonality? The cell is the smallest unit with the properties of life, but what is it, exactly, that makes a cell, or an organism that consists of them, alive? According to evolutionary biologist Gerald Joyce, the simplest definition of life might well be “that which is squishy.” He says, “Life, after all, is protoplasmic and cellular. It is made up of cells and organic stuff and is undeniably squishy.”

Defining life more unambiguously than “squishy” is challenging, if not impos- sible. Even deciding what sets the living apart from the nonliving can be tricky. For example, living things have a high proportion of the organic molecules of life, but so do the remains of dead organisms in seams of coal. Living things use energy to reproduce themselves, but computer viruses, which are arguably not alive, can do that too.

So how do biologists, who study life as a profession, define it? The short answer is that their best definition is a long list of properties that collectively apply to living things, and not to nonliving things. You already know about two of these properties:

1. Living things make and use the organic molecules of life . . . 2. . . . and they consist of one or more cells.

The remainder of this book details the other properties of life:

3. Living things engage in self-sustaining biological processes such as metabolism and homeostasis . . . 4. . . . and they change over their lifetime, for example by maturing and aging . . . 5. . . . and they use DNA as their hereditary material when they reproduce . . . 6. . . . and they have the collective capacity to change over successive generations, for example by adapting to environmental pressures.

Take-Home Message 3.6 What, exactly, is life?

• We describe the characteristic of “life” in terms of properties that are collectively unique to living things.

• organisms make and use the organic molecules of life. DNA is their hereditary material.

• In living things, the molecules of life are organized as one or more cells that engage in self-sustaining biological processes.

• Living things change over lifetimes, and also over successive generations.

“Life . . . is made up of cells and organic stuff and is undeniably squishy.”

Section 3.1 A huge number of bacteria live in and on the human body. Most of them are helpful; only a few types can cause disease. Contamination of food with disease-causing bacteria can result in illness that is sometimes fatal.

Section 3.2 By the cell theory, all organisms consist of one or more cells; the cell is the smallest unit of life; each new cell arises from another, preexisting cell; and a cell passes hereditary material to its offspring. All cells start out life with cytoplasm, DNA, and a plasma

membrane that controls the types and kinds of substances that cross it. Most have many additional components. A eukaryotic cell’s DNA is contained within a nucleus, which is a membrane- enclosed organelle. the surface-to-volume ratio limits cell size and influences cell shape. Different types of microscopes and techniques reveal different internal and external details of cells.

Section 3.3 A cell membrane is a lipid bilayer (of mainly phospholipids) with many other molecules attached or embedded in it. A bacterial or eukaryotic cell membrane can be described as a fluid mosaic;

archaeal membranes are not fluid. Proteins carry out most membrane functions. All cell membranes have enzymes, and all have transport proteins that help substances move across the membrane. Plasma membranes also incorporate adhesion proteins that lock cells together in tissues. Plasma membranes and some internal membranes have receptor proteins that trigger a change in cell activities in response to a stimulus.

Section 3.4 Bacteria and archaea (prokaryotes) are single- celled organisms with no nucleus. All have DNA and ribosomes. Many also have a protective, rigid cell wall and a sticky capsule, and some have motile structures (flagella) and other projections (pili). they often have plasmids in addition to the single circular molecule of DNA. Bacteria and other microorganisms may live together in a shared mass of slime as a biofilm.

Section 3.5 the nucleus in cells of eukaryotes (protists, fungi, plants, and animals) protects and controls access to the cell’s DNA. the nucleus has a nuclear envelope, a double membrane studded with pores through which molecules pass into and out of the

nucleus. A typical eukaryotic cell has many other membrane- enclosed organelles, including the endoplasmic reticulum (ER), a continuous system of sacs and tubes extending from the nuclear envelope. Polypeptides made in ribosome-studded rough er pass to smooth er, which makes lipids and breaks down carbohydrates

and fatty acids. Golgi bodies modify proteins and lipids before sorting them into vesicles. enzymes in peroxisomes break down substances such as amino acids, fatty acids, and toxins. enzymes in lysosomes break down cellular wastes and debris. Mitochondria produce AtP by aerobic respiration; chloroplasts carry out photosynthesis.

elements of a cytoskeleton reinforce, organize, and move cell structures and often the entire cell. Cytoskeletal elements include microtubules, microfilaments, and intermediate filaments. Interactions

between AtP-driven motor proteins and microtubules bring about movement of cilia and eukaryotic flagella. elongating microfilaments bring about movement of pseudopods. Intermediate filaments lend structural support to cells and tissues, and they help support the nuclear membrane.

A secreted mixture of materials forms extracellular matrix (ECM) that has different functions depending on the cell type. In animals, a secreted basement membrane supports and organizes cells in tissues. Among the eukaryotes, plant cells, fungi, and many protists secrete a cell wall around their plasma membrane. Many eukaryotic cell types also secrete a protective cuticle.

Cell junctions connect cells to one another and to their environment. Plasmodesmata (in plants) and gap junctions (in animals) connect the cytoplasm of adjacent cells. Also in animal cells, adhering junctions that connect to cytoskeletal elements fasten cells to one another and to basement membrane. tight junctions form a waterproof seal between cells.

Section 3.6 All living things share a characteristic set of features. they make and use the molecules of life; they consist of one or more cells that engage in self- sustaining biological processes; they change over their lifetime; and they pass their DNA to offspring that can

change over generations.

answers in appendix i

1. All cells have these three things in common: a. cytoplasm, DNA, and organelles with membranes b. a plasma membrane, DNA, and a nuclear envelope c. cytoplasm, DNA, and a plasma membrane d. a cell wall, cytoplasm, and DNA

2. unlike eukaryotic cells, prokaryotic cells . a. have no plasma membrane c. have no nucleus b. have rNA but not DNA d. a and c

Self-Quiz

Summary

CELL STruCTurE ChaptER 3 61

P. L. Walne and J. H. Arnott, Planta, 77:325–354, 1967.

1. In a classic episode of Star Trek, a gigantic amoeba engulfs an entire starship. Spock blows the cell to bits before it has a chance to reproduce. think of at least one problem a biologist would have with this particular scenario.

2. In plants, the cell wall forms as a young plant cell secretes polysaccharides onto the outer surface of its plasma mem- brane. Being thin and pliable, this primary wall allows the cell to enlarge and change shape. In mature woody plants, cells in some tissues deposit material onto the primary wall’s inner sur- face. Why doesn’t this secondary wall form on the outer surface of the primary wall?

1. What type of micrograph is shown below? Is the organism pic- tured prokaryotic or eukaryotic? How can you tell?

3. every cell is descended from another cell. this idea is part of . a. evolution c. the cell theory b. the theory of heredity d. cell biology

4. the surface-to-volume ratio . a. does not apply to prokaryotic cells c. constrains cell size b. is part of the cell theory d. b and c

5. true or false? Some protists start out life with no nucleus.

6. Cell membranes consist mainly of and . a. lipids; carbohydrates c. lipids; carbohydrates b. phospholipids; proteins d. phospholipids; eCM

7. Which of the following statements is correct? a. ribosomes are only found in bacteria and archaea. b. Some animal cells are prokaryotic. c. Only eukaryotic cells have mitochondria. d. the plasma membrane is the outermost boundary of

all cells. e. Most membrane functions are carried out by phospholipids.

8. In a lipid bilayer, the of all the lipid molecules are sandwiched between all of the . a. hydrophilic tails; hydrophobic heads b. hydrophilic heads; hydrophilic tails c. hydrophobic tails; hydrophilic heads d. hydrophobic heads; hydrophilic tails

9. the main function of the endomembrane system is . a. building and modifying proteins and lipids b. isolating DNA from toxic substances c. secreting extracellular matrix onto the cell surface d. producing AtP by aerobic respiration

10. enzymes contained in break down worn-out organelles, bacteria, and other particles. a. lysosomes c. endoplasmic reticulum b. mitochondria d. peroxisomes

11. Put the following structures in order according to the pathway of a secreted protein: a. plasma membrane c. endoplasmic reticulum b. Golgi bodies d. post-Golgi vesicles

12. No animal cell has a . a. plasma membrane c. lysosome b. flagellum d. cell wall

13. connect the cytoplasm of plant cells. a. Plasmodesmata c. tight junctions b. Adhering junctions d. Adhesion proteins

14. Which of the following organelles contains no DNA? Choose all that are correct. a. nucleus c. mitochondrion b. Golgi body d. chloroplast

15. Match each cell component with its main function. mitochondrion a. connection chloroplast b. protective covering ribosome c. AtP production nucleus d. protects DNA cell junction e. protein synthesis flagellum f. photosynthesis cuticle g. movement

Critical thinking

Visual Question

4.1 A Toast to Alcohol Dehydrogenase 64

4.2 Life Runs on Energy 65

4.3 Energy in the Molecules of Life 66

4.4 How Enzymes Work 68

4.5 Diffusion and Membranes 73

4.6 Membrane Transport Mechanisms 75

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Application 4.1 A Toast to Alcohol Dehydrogenase Most college students are under the legal drinking age, but alcohol abuse continues to be the most serious drug problem on college campuses throughout the United States. Recent surveys polled tens of thousands of undergraduates about their drink- ing habits, and more than half of them reported regularly consuming five or more alcoholic beverages within a two-hour period—a self-destructive behavior called binge drinking. Drinking large amounts of alcohol in a brief period of time is an extremely risky behavior, both for the drinkers and people around them. Every year, around 600,000 students injure themselves while under the influence of alcohol; intoxicated students physically assault 690,000 people and sexually assault 97,000 others. Binge drinking is responsible for killing or causing the death of 1,825 stu- dents per year.

Before you drink, consider what you are consuming. All alcoholic drinks—beer, wine, hard liquor—contain the same psychoactive ingredient: ethanol. Almost all ingested ethanol ends up in the liver, a large organ in the abdomen with many important functions. Liver cells make an enzyme, alcohol dehydrogenase (ADH), which is part of a metabolic pathway that detoxifies alcohols (Figure 4.1). This path- way evolved long before humans began to consume alcoholic beverages. Its main function in our bodies is to break down the tiny amount of alcohol that we encoun- ter naturally: Foods such as ripe fruit contain it, and it also forms in our bodies as a metabolic by-product of body cells and gut bacteria.

ADH converts ethanol to acetaldehyde, an organic compound even more toxic than ethanol and the most likely source of various hangover symptoms. A second enzyme converts the toxic acetaldehyde to acetate, which is a nontoxic salt. In the average healthy adult human, these two enzymes can detoxify between 7 and 14 grams of ethanol per hour. The average alcoholic beverage contains between 10 and 20 grams of ethanol, which is why having more than one drink in any two-hour interval may result in a hangover.

Putting more alcohol into your body than your enzymes can detoxify damages it more permanently than a hangover, however. Ethanol breakdown harms liver cells, so the more a person drinks, the fewer liver cells are left to do the breaking down. Ethanol also interferes with normal processes of metabolism. For example, oxygen that would ordinarily take part in breaking down fatty acids is diverted to breaking down the ethanol. As a result, fats tend to accumulate as large globules in the tissues of heavy drinkers. Long-term heavy drinking causes alcoholic hepatitis,

Figure 4.1 Alcohol dehydrogenase. Left, this enzyme helps the body break down toxic molecules such as ethanol, making it possible for humans to drink beer, wine, and other alcoholic beverages.

Right, a tailgate party at a Notre Dame– Alabama football game. Indiana state police arrested 138 Notre Dame stu- dents for underage drinking at tailgate parties during 2012. © Al Diaz/Miami Herald/MCT via Getty Images.

alcohol dehydrogenase

ENERgy AND METAboLIsM ChApter 4 65

energy The capacity to do work.

first law of thermodynamics Energy cannot be cre- ated or destroyed.

second law of thermodynamics Energy tends to disperse spontaneously.

4.2 Life Runs on Energy reMeMBer: A one-way flow of energy and a cycling of nutrients sustain life’s orga- nization (section 1.3). A law of nature describes something that occurs without fail, but our explanation of why it occurs is incomplete (1.6).

Energy is formally defined as the capacity to do work, but this definition is not very satisfying. Even the brilliant physicists who study it cannot say exactly what it is. However, we do have an intuitive understanding of energy just by thinking about familiar forms of it, such as light, heat, electricity, and motion. We also understand intuitively that one form of energy can be converted to another. Think about how an automobile changes the chemical energy of gasoline into the energy of motion (kinetic energy), or how a lightbulb changes electricity into light.

The formal study of heat and other forms of energy is called thermo- dynamics (therm means heat; dynam means power). By making careful measurements, thermodynamics researchers discovered that the total amount of energy before and after every conversion is always the same. In other words, energy cannot be created or destroyed—a phenomenon that is the first law of thermodynamics. Energy also tends to spread out, or disperse, until no part of a system holds more than another part. In a kitchen, for example, heat always flows from a hot pan to cool air until the temperature of both is the same. We never see cool air raising the temperature of a hot pan. The tendency of energy to spread out spontaneously is the second law of thermodynamics.

Work occurs as a result of energy transfers. Consider how it takes work to push a box across a floor. In this case, a body (you) transfers energy to another body (the box) to make it move. Similarly, a plant cell works to make sugars. Inside the cell, one set of molecules harvests energy from light, then transfers it to another set of molecules. A second set of molecules uses the energy to build sugars from carbon dioxide and water. This particular energy transfer involves the conversion of light energy to chemical energy. Most other types of cellular work occur by the transfer of chemical energy from one molecule to another.

As you learn about such processes, remember that every time energy is trans- ferred, a bit of it disperses—usually in the form of heat. As a simple example, a typi- cal incandescent lightbulb converts only about 5 percent of the energy of electricity into light. The remaining 95 percent of the energy ends up as heat that disperses from the bulb.

a disease characterized by inflammation and destruction of liver tissue. It also causes cirrhosis, a condition in which the liver becomes so scarred, hardened, and filled with fat that it loses its function. (The term cirrhosis is from the Greek kirros, meaning “orange-colored,” after the abnormal skin color of people with the disease.) A cirrhotic liver can no longer produce the protein albumin, so the solute balance of body fluids is disrupted, and the legs and abdomen swell with watery fluid. It can no longer remove drugs and other toxins from the blood, so they accumulate in the brain—which impairs mental functioning and alters personality. Restricted blood flow through a cirrhotic liver causes veins to enlarge and rupture, so internal bleeding is a risk. The damage to the body results in a heightened susceptibility to diabetes and liver cancer. Once cirrhosis has been diagnosed, a person has about a 50 percent chance of dying within 10 years (Figure 4.2).

Figure 4.2 Gary reinbach. The 22-year-old died from alcoholic liver disease shortly after this photograph was taken, in 2009. The odd color of his skin is a symptom of cirrhosis.

Transplantation is a last-resort treatment for a failed liver, but there are not enough liver donors for everyone who needs a transplant. Reinbach was refused a trans- plant that may have saved his life because he had not abstained from drinking for the prior 6 months. Stuart Clark/The Sunday Times/nisyndication.

66 Unit 1 HoW CELLs WoRk

Dispersed heat is not useful for doing work, and it is not easily converted to a more useful form of energy (such as electricity). Because some energy in every transfer disperses as heat, and heat is not useful for doing work, we can say that the total amount of energy in the universe available for doing work is always decreasing.

Is life an exception to this inevitable flow? An organized body is hardly dis- persed. Energy becomes concentrated in each new organism as the molecules of life organize into cells. Even so, living things constantly use energy—to grow, to move, to acquire nutrients, to reproduce, and so on—and some energy is lost in every one of these processes (Figure 4.3). Unless the losses are replenished with energy from another source, life’s complex organization will end.

The energy that fuels most life on Earth comes from the sun. That energy flows through producers such as plants, then consumers such as animals (Figure 4.3). During this journey, the energy is transferred many times. With each transfer, some energy escapes as heat until, eventually, all of it is permanently dispersed. However, the second law of thermodynamics does not say how quickly the dispersal has to happen. Energy’s spontaneous dispersal is resisted by chemical bonds. The energy in chemical bonds is a type of potential energy, which is energy stored in the position or arrangement of objects in a system (Figure 4.4). Think of the bonds in the count- less molecules that make up your skin, heart, liver, fluids, and other body parts. Those bonds hold the molecules, and you, together—at least for the time being.

Take-Home Message 4.2 What is energy?

• Energy, which is the capacity to do work, cannot be created or destroyed. • Energy disperses spontaneously. • Energy can be transferred between systems or converted from one form to another,

but some is lost (as heat, typically) during every exchange. • sustaining life’s organization requires ongoing energy inputs to counter energy loss.

organisms stay alive by replenishing themselves with energy they harvest from someplace else.

4.3 Energy in the Molecules of Life reMeMBer: A chemical formula (section 2.3) indicates unvarying proportions of elements in a molecule. Reactions are processes of molecular change (2.6). Cellulose consists of chains of glucose monomers (2.7).

All cells store and retrieve energy in chemical bonds of the molecules of life, and these activities occur by way of reactions. During a reaction, one or more reactants (molecules that enter the reaction and become changed by it) become one or more products (molecules that are produced by the reaction). Intermediate molecules may form between reactants and products. We show a reaction as an equation in which an arrow points from reactants to products:

P R O D U C E R S

C O N S U M E R S

A. energy in sunlight reaches environments on Earth. Producers in those environments capture some of its energy and convert it to other forms that can drive cellular work.

C. energy Out With each energy transfer, some energy escapes into the environ- ment, mainly as heat. Living things do not use heat to drive cellular work, so energy flows through the world of life in one direction overall.

B. some of the energy captured by producers ends up in the tissues of consumers.

Figure 4.3 energy flow through the world of life.

2H2O (water)

�

(hydrogen) 2H2 O2

(oxygen)

Figure 4.4 illustration of potential energy. by opposing gravity’s downward pull, the rope keeps the man from falling. similarly, a chemical bond that attaches two atoms keeps them from flying apart. © Greg Epperson/Shutterstock.com.

ENERgy AND METAboLIsM ChApter 4 67

A number before a chemical formula in such equations indicates the number of molecules; a subscript indicates the number of atoms of that element per molecule. Note that atoms shuffle around in a reaction, but they never disappear: The same number of atoms that enter a reaction remain at the reaction’s end.

Every chemical bond holds a certain amount of energy. That is the amount of energy required to break the bond, and it is also the amount of energy released when the bond forms. The particular amount of energy held by a bond depends on which elements are taking part in it. For example, two covalent bonds—one between an oxygen and a hydrogen atom in a water molecule, the other between two oxygen atoms in molecular oxygen (O2)—both hold energy, but different amounts of it. In most reactions, the energy of the reactants differs from the energy of the products. If the reactants have less energy than the products, the reaction will not proceed without a net energy input (Figure 4.5

). If the reactants have more energy than the products, the reaction will end with a net release of energy

Why Earth Does Not Go Up in Flames The molecules of life release energy when they combine with oxygen. Think of how a spark ignites wood in a camp- fire. Wood is mostly cellulose, which consists of long chains of repeating glucose monomers. A spark starts a reaction that converts cellulose (in wood) and oxygen (in air) to water and carbon dioxide. This reaction releases a lot of energy—enough to initiate the same reaction with other cellulose and oxygen molecules. That is why wood keeps burning after it has been lit (Figure 4.6A).

Earth is rich in oxygen—and in potential energy-releasing reactions. Why doesn’t it burst into flames? Luckily, chemical bonds do not break without at least a small input of energy, even in an energy-releasing reaction. We call this input activa- tion energy. Activation energy, the minimum amount of energy required to get a chemical reaction started, is a bit like a hill that reactants must climb before they can coast down the other side to become products (Figure 4.6B).

Both energy-requiring and energy-releasing reactions have activation energy, but the amount varies with the reaction. Consider guncotton (nitrocellulose), a highly explosive derivative of cellulose. Christian Schönbein accidentally discovered a way to manufacture it when he used his wife’s cotton apron to wipe up a nitric acid spill on his kitchen table, then hung it up to dry next to the oven. The apron exploded, and being a chemist in the 1800s, Schönbein was thrilled. He immediately

activation energy Minimum amount of energy required to start a reaction.

product A molecule that is produced by a reaction.

reactant A molecule that enters a reaction and is changed by participating in it.

B. Most reactions will not begin without an input of acti- vation energy, which is shown as a bump in an energy hill. The graph shows an energy-releasing reaction; energy-requiring reactions also have activation energy.

A. Wood continues to burn after it has been lit because the combustion reaction between cellulose molecules in wood and oxygen molecules in air releases enough energy to trigger the reaction again with other molecules. Activation energy keeps this and other energy-releasing reactions from starting without an energy input.

Activation energy

Reactants: 2H2 � O2

Products: 2H2O

Time

E ne

rg y

Difference between energy of

reactants and products

Figure 4.6 Activation energy. (A) Tero Hakala/Shutterstock.com.

Activation energy

Reactants: 2H2 � O2

Products: 2H2O

Time E

ne rg

Difference between energy of

reactants and products

Figure 4.5 energy inputs and outputs in chemical reactions.

some reactions convert molecules with lower energy to molecules with higher energy, so they require a net energy input in order to proceed.

other reactions convert molecules with higher energy to molecules with lower energy, so they end with an energy release.

carbon dioxide CO2

water H2O

oxygen O2

E ne

rg y

glucose C6H12O6

6 6

Figure it Out: Which law of thermo- dynamics explains energy inputs and outputs in chemical reactions?

Answer: The first law

energy output

energy input

68 Unit 1 HoW CELLs WoRk

Take-Home Message 4.3 how do cells use energy?

• Cells store and retrieve energy by making and breaking chemical bonds. • some reactions require a net input of energy. others end with a net release of energy. • Most chemical reactions require an input of activation energy to begin.

4.4 How Enzymes Work reMeMBer: Electrons carry energy in incremental amounts (section 2.2). The number of hydrogen ions in a fluid determines its pH (2.5). Molecules jiggle faster at higher temperatures (2.4). Enzymes speed reactions without being changed by them; metabolism includes all the enzyme-mediated reactions by which cells acquire and use energy as they build and break down organic molecules (2.6). A protein’s func- tion arises from and depends on its three-dimensional shape, which is held together by hydrogen bonds; when a protein denatures, it loses its shape and its function (2.9). ATP has an important metabolic role as an energy carrier (2.10).

The Need for Speed Metabolism requires enzymes. Why? Consider that a molecule of glucose can break down to carbon dioxide and water on its own, but the process might take decades. That same conversion takes just seconds inside your cells. Enzymes make the difference. An enzyme makes a reaction run much faster than it would on its own. The enzyme is unchanged by participating in the reaction, so it can work again and again.

Some enzymes are RNAs, but most are proteins. Each kind of enzyme interacts only with specific reactants, or substrates, and alters them in a specific way. Such specificity occurs because an enzyme’s polypeptide (or nucleotide) chains fold to form a pocket called an active site, where substrates bind and a reaction proceeds (Figure 4.8). An active site is complementary in shape, size, polarity, and charge to the enzyme’s substrate. That fit is the reason why each enzyme acts in a specific way on a specific substrate (Figure 4.9).

tried marketing guncotton as a firearm explosive, but it was too unstable to manu- facture. So little activation energy is needed to make guncotton react with oxygen that it tends to explode unexpectedly. Several manufacturing plants burned to the ground before guncotton was abandoned for use as a firearm explosive. The substi- tute: gunpowder, which has a higher activation energy for a reaction with oxygen.

Energy In, Energy Out Cells store energy by running energy-requiring reactions that build organic compounds (Figure 4.7A). For example, light energy drives pho- tosynthesis, a pathway that produces glucose from carbon dioxide and water. Unlike light, glucose can be stored in a cell. Cells harvest energy by running energy-releasing reactions that break the bonds of organic compounds (Figure 4.7B). Most cells do this when they carry out aerobic respiration, a pathway that releases the energy of glucose by breaking the bonds between its carbon atoms. You will see in the next section how cells use energy released from some reactions to drive others (we return to the reactions of photosynthesis and aerobic respiration in Chapter 5).

Figure 4.7 Cells store and retrieve energy in the chemical bonds of organic molecules.

A. Cells store energy in the chemical bonds of organic compounds.

B. Cells retrieve energy stored in the chemical bonds of organic compounds.

energy out

organic compounds (carbohydrates, fats, proteins)

small molecules (e.g., carbon dioxide, water)

energy-requiring reactions

energy-releasing reactions

energy in

energy out

organic compounds (carbohydrates, fats, proteins)

small molecules (e.g., carbon dioxide, water)

energy-requiring reactions

energy-releasing reactions

energy in

Figure 4.8 example of an active site. For simplicity, enzymes are often drawn as blobs or geo- metric shapes. This model shows the actual contours of an active site in hexo kinase, an enzyme that adds a phosphate group to glucose and other six-carbon sugars. PDB ID: 1GZX; Paoli, M., Liddington, R., Tame, J., Wilinson, A., Dodson, G.; Crystal Structure of T state hemoglobin with oxygen bound at all four haems. J. Mol.Bio., v256, pp. 775–792, 1996.

A. A glucose molecule meets up with a phosphate in the active site of a hexokinase enzyme.

B. The reaction between glucose and phosphate produced glucose-6-phosphate, shown leaving the active site.

ENERgy AND METAboLIsM ChApter 4 69

active site Pocket in an enzyme where substrates bind and a reaction occurs.

substrate of an enzyme, a reactant that is specifically acted upon by the enzyme.

An enzyme speeds a reaction by reducing activation energy, so it lowers the barrier that prevents the reaction from proceeding. When we talk about activation energy, we are really talking about the energy required to bring reactant bonds to the breaking point. An active site can bring reactants to this state by (for example) holding them in a certain position, squeezing them, or redistributing their charge.

Factors That Influence Enzyme Activity Environmental factors such as pH, temperature, salt, and pressure influence an enzyme’s shape, and so influence its function. Each enzyme works best in a particular range of conditions that reflect the environment in which it evolved.

Consider pepsin, a digestive enzyme that works best at low pH (Figure 4.10A). Pepsin begins the process of protein digestion in the very acidic environment of the stomach (pH 2). During digestion, the stomach’s contents pass into the small intes- tine, where the pH rises to about 7.5. Pepsin denatures (unfolds) above pH 5.5, so this enzyme becomes inactive in the small intestine. Here, protein digestion contin- ues with the assistance of trypsin, an enzyme that functions well at the higher pH.

Adding heat boosts energy, which is why the jiggling motion of atoms and molecules increases with temperature. The greater the energy of reactants, the closer they are to reaching activation energy. Thus, the rate of an enzymatic reaction typically increases with temperature—but only up to a point. An enzyme denatures above a characteristic temperature. Then, the reaction rate falls sharply as the shape of the enzyme changes and it stops working (Figure 4.10B). Body temperatures above 42°C (107.6°F) adversely affect the function of many of your enzymes, which is why such severe fevers are dangerous.

The activity of many enzymes is also influenced by the amount of salt in the surrounding fluid. Too little salt, and polar parts of the enzyme attract one another so strongly that the molecule’s shape changes. Too much salt interferes with the hydrogen bonds that hold the enzyme in its characteristic shape, so the enzyme denatures.

Figure 4.10 enzymes, temperature, and ph. Each enzyme works best within a characteristic range of conditions—generally, the same environmental conditions in which the enzyme normally occurs.

Figure it Out: At what temperature does the E. coli DNA poly merase work fastest?

Answer: About 37°C

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Temperature (°C) 20 40 60 80 100

T. aquaticus polymerase

E. coli polymerase

B. Temperature-dependent activity of an enzyme from two bacteria: E. coli, which inhabits the human gut (normally 37°C); and Thermus aquaticus, which lives in hot springs around 70°C.

pH 2 4 6 8 10

pepsin trypsin

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A. The pH-dependent activity of two digestive enzymes. Pepsin acts in the stomach, where the normal pH is 2. Trypsin acts in the small intestine, where the pH is normally around 7.5.

Figure 4.9 how an active site works.

A. An active site binds substrates that are complementary in shape, size, polarity, and charge.

B. binding at an active site squeezes substrates together, influences their charge, or causes some change that lowers activation energy, and the reac- tion proceeds.

C. The product leaves the active site after the reaction is finished. The enzyme is unchanged, so it can work again.

enzyme substrates

Cells use energy released from some reactions to drive others.

70 Unit 1 HoW CELLs WoRk

Regulatory molecules (or ions) enhance or inhibit the activity of many enzymes. Some of these substances exert their effects by binding directly to an active site; others bind elsewhere on the enzyme. In the latter case, binding of the regulatory molecule alters the overall shape of the enzyme (Figure 4.12).

Cofactors Most enzymes (and many other proteins) can function properly only with assistance from metal ions or small organic molecules. These helpers are called cofactors. Many dietary vitamins and minerals are essential because they are cofac- tors or become converted into cofactors. Coenzymes, which are organic cofactors, carry chemical groups, atoms, or electrons from one reaction to another, and often into or out of organelles. In some reactions, coenzymes stay tightly bound to the enzyme. In others, they participate as separate molecules.

One tough Bug

The genus Ferroplasma consists of a few species of acid-loving archaea. one species, F. acidarmanus, was discovered to be the main component of slime streamers (a type of biofilm) deep inside an abandoned California copper mine (Figure 4.11A).

F. acidarmanus cells use an ancient energy-harvesting pathway that combines oxygen with iron–sulfur compounds in minerals such as pyrite. This reaction dissolves the min- erals, so groundwater that seeps into the mine ends up with extremely high concentrations of metal ions such as copper, zinc, cadmium, and arsenic. The reaction also produces sulfuric acid, which lowers the pH of the water around the cells to zero.

Despite living in an environment with a composition similar to hot battery acid, F. acidarmanus cells maintain their internal pH at a cozy 5.0. Thus, researchers investigating Ferroplasma metabolic enzymes were surprised to discover that most of the cells’ enzymes function best at very low pH (Figure 4.11b).

1. What does the dashed line signify? 2. of the four enzymes profiled in the graph,

how many function optimally at a pH lower than 5? How many retain significant func- tion at pH 5?

3. What is the optimal pH for F. acidarmanus carboxylesterase?

Figure 4.11 ph anomaly of Ferroplasma acidarmanus enzymes. (A) Dr. Katrina J. Edwards; (B) From Golyshina et al., Environmental Microbiology, 8(3): 416–425. © 2006 John Wiley and Sons. Used with permission of the publisher.

Digging Into Data

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pH pH pH pH 3 4 5 60 1 2 3 4 5 60 1 2 3 4 5 6 70 1 2

a-glucosidase glyFa1 glyFa2carboxylesterase

3 4 5 6 70 1 2

A. Deep inside one of the most toxic sites in the United states: Iron Mountain Mine, in California. The water in this stream, which is about 1 meter (3 feet) wide in this photo, is hot (around 40°C, or 104°F), heavily laden with arsenic and other toxic metals, and has a pH of zero. slime streamers growing in it are a biofilm dominated by a species of archaea, Ferroplasma acidarmanus.

B. pH profiles of four enzymes isolated from F. acidarmus. Researchers had expected these enzymes to func- tion best at the cells’ cytoplasmic pH (5.0).

Figure 4.12 regulatory molecule binding to enzymes. some types of regulatory molecules (red) bind to an enzyme in a place other than the active site. This binding changes the shape of the enzyme in a way that enhances or inhibits its function.

enzyme substrate

regulatory molecules

ENERgy AND METAboLIsM ChApter 4 71

Unlike enzymes, many coenzymes are modified by taking part in a reaction. They are regenerated in separate reactions. Consider NAD+ (nicotinamide adenine dinucleotide), a coenzyme derived from niacin (vitamin B3). NAD

+ can accept elec- trons and hydrogen atoms, thereby becoming NADH. When electrons and hydro- gen atoms are removed from NADH, NAD+ forms again:

In cells, the nucleotide ATP (adenosine triphosphate) functions as a coenzyme in many reactions. Bonds between phosphate groups hold a lot of energy, and ATP has two of these bonds holding its three phosphate groups together (Figure 4.13A). When a phosphate group is transferred to or from a nucleotide, energy is transferred along with it. Thus, the nucleotide can receive energy from an energy-releasing reaction, and it can also donate energy that contributes to the “energy in” part of

an energy-requiring reaction. ATP is such an important currency in a cell’s energy economy that we use a cartoon coin to symbolize it.

A reaction in which a phosphate group is transferred from one molecule to another is called a phosphorylation. ADP (adenosine diphosphate) forms when an enzyme transfers a phosphate group from ATP to another molecule (Figure 4.13B). Cells constantly run this reaction in order to drive a variety of energy-requiring reactions. Thus, they constantly have to replenish their stockpile of ATP—by run- ning energy-releasing reactions that phosphorylate ADP. This cycle of using and replenishing ATP couples energy-requiring reactions with energy-releasing ones. As you will see in Chapter 5, cells harvest energy from organic compounds by run- ning metabolic pathways that break them down. Energy that cells harvest in these pathways is not released to the environment, but rather stored in the high-energy phosphate bonds of ATP molecules and in electrons carried by coenzymes. The ATP and the coenzymes are then used to drive many of the energy-requiring reactions that a cell runs.

Metabolic Pathways Building, rearranging, or breaking down an organic sub- stance often occurs stepwise, in a series of enzymatic reactions called a metabolic pathway. Some metabolic pathways are linear, meaning that the reactions run straight from reactant to product:

Other reactions are cyclic. In a cyclic pathway, the last step regenerates a reactant of the first step (left).

Controlling Metabolism Cells conserve energy and resources by making only what they need at any given moment—no more, no less. Several mechanisms help a cell main-

tain, raise, or lower its production of thousands of different substances. Consider that reactions do not only run from reactants to products. Many also run in re verse at the same time, with some of the products being converted back into reactants. The rates of the forward and reverse reactions often depend on the concentrations of reactants and products: A high concentration of reactants pushes the reaction in the forward direction; a high concentration of products pushes it in reverse.

NAD+ � electrons � H+ NAD+ � electrons � H+NADH

coenzyme An organic cofactor.

cofactor A molecule or metal ion that associates with a protein and is necessary for its function.

metabolic pathway series of enzyme-mediated reac- tions by which cells build, remodel, or break down an organic molecule.

phosphorylation A phosphate-group transfer.

A. bonds between phosphate groups hold a lot of energy. ATP has two of these bonds.

B. ADP forms in a reaction that removes a phosphate group from ATP. Energy released in this reaction drives other reactions that are the stuff of cellular work. ATP forms again in reactions that phosphorylate ADP.

Figure 4.13 Atp as an energy carrier.

reactant

intermediate

product

intermediate

enzyme 2

enzyme 3 enzyme 1

reactant intermediate intermediate enzyme 1 enzyme 2

product enzyme 3

ATP

adenine

ribose

three phosphate groups

ATP

ADP + phosphate

energy in energy out

72 Unit 1 HoW CELLs WoRk

oxygen

glucose

H+

water

carbon dioxide

e–

Take-Home Message 4.4 how do enzymes work in metabolic pathways?

• binding at an enzyme’s active site causes substrate bonds to reach their breaking point, and the reaction can run spontaneously to completion.

• Each enzyme works best within a characteristic range of environmental conditions. Many enzymes require the assistance of cofactors.

• ATP often couples reactions that release energy with reactions that require energy. • A metabolic pathway is a series of enzyme-mediated reactions that builds, breaks down,

or remodels an organic molecule. some pathways involve electron transfer chains. • Cells conserve energy and resources by producing only what they require at a given

time. This metabolic control arises from mechanisms that regulate individual enzymes and often entire pathways.

Other mechanisms more actively regulate pathways. Regulatory substances gov- ern how fast enzyme molecules are made, or influence the activity of enzymes that have already been built. Regulation of a single enzyme can affect an entire metabolic pathway. In some cases, the end product of a series of enzymatic reactions inhibits the activity of one of the enzymes in the series (Figure 4.14). This type of regulatory mechanism, in which a change that results from an activity decreases or stops the activity, is called feedback inhibition.

Electron Transfers The bonds of organic molecules hold a lot of energy that can be released in a reaction with oxygen. Burning is one type of reaction with oxygen, and it releases the energy of organic molecules all at once (Figure 4.15A). Cells use oxygen to break the bonds of organic molecules, but they have no way to harvest the sudden burst of energy that occurs during burning. Instead, they break the molecules apart in pathways that release the energy in small, manageable steps. Most of these steps are electron transfers, in which one molecule accepts electrons from another. Energy is harvested in these reactions. In the next chapter, you will learn about the importance of this process in electron transfer chains. An electron transfer chain is a series of membrane-bound enzymes and other molecules that give up and accept electrons in turn. Electrons are at a higher energy level when they enter a chain than when they leave. Energy given off by an electron as it drops to a lower energy level is harvested by molecules of the electron transfer chain to do cellular work (Figure 4.15B).

Figure it Out: Is this a cyclic or a linear pathway? Answer: This is a linear pathway.

Figure 4.14 Feedback inhibition. In this example, three different enzymes act in sequence to convert a substrate to a product. The product inhibits the activity of the first enzyme.

reactant intermediate intermediate enzyme 1 enzyme 2 enzyme 3

productX

B. In cells, glucose reacts with oxygen in a stepwise fashion that involves an electron transfer chain, repre- sented here by a staircase. Energy is released in amounts that cells are able to use.

An input of activation energy splits glucose into carbon dioxide, electrons, and hydrogen ions (H+).

Electrons lose energy ( ) as they pass from one molecule to the next in an electron transfer chain. That energy is harnessed for cellular work.

Electrons, hydrogen ions, and oxygen combine to form water.

A. glucose reacts with oxygen (burns). Energy in the form of light and heat is released all at once as carbon dioxide and water form.

ENERgy AND METAboLIsM ChApter 4 73

lipid bilayer

oxygen

carbon dioxide

water

ions; glucose and other polar organic molecules

gases

4.5 Diffusion and Membranes reMeMBer: An ion carries charge (section 2.2). Atoms and molecules move faster at higher temperatures (2.4). The amount of a solute per unit volume of solution is its concentration (2.4). The number of hydrogen ions in a fluid determines its pH (2.5). Lipid bilayers are impermeable to ions and polar molecules (3.3).

Metabolic pathways require the participation of molecules and ions that must move across membranes and through cells. Diffusion is the spontaneous spreading of molecules or atoms (left), and it is an essential way in which substances move into, through, and out of cells. Diffusion occurs because an atom or molecule is always jiggling, and this internal movement causes it to randomly bounce off of nearby objects, including other atoms or molecules. Rebounds from such collisions propel solutes through a liquid, resulting in a gradual and complete mixing. How fast this occurs depends on five factors:

1. Concentration. A difference in solute concentration between adjacent regions of solution is called a concentration gradient. Solutes tend to diffuse “down” their concentration gradient, from a region of higher concentration to one of lower con- centration. Why? Consider that moving objects (such as molecules) collide more often when they are more crowded. Thus, during a given interval, more molecules get bumped out of a region of higher concentration than get bumped into it. 2. Temperature. Atoms and molecules jiggle faster at higher temperature, so they collide more often. Thus, diffusion occurs more quickly at higher temperatures. 3. Size. It takes more energy to move a large object than it does to move a small one, so ions and small molecules diffuse more quickly than large molecules. 4. Charge. Each ion or charged molecule in a fluid contributes to the fluid’s over- all electric charge. A difference in charge between two regions of fluid can affect the rate and direction of diffusion between them. For example, positively charged substances (such as sodium ions) will tend to diffuse toward a region with an over- all negative charge. 5. Pressure. Pressure squeezes objects—including atoms and molecules—closer together. Atoms and molecules that are more crowded collide and rebound more frequently. Thus, diffusion occurs faster at higher pressures.

Semipermeable Membranes Lipid bilayers are selectively permeable, which means that they are permeable to some substances and not others. Specifically, water, gases, and hydrophobic molecules can diffuse directly through a lipid bilayer; most solutes—ions and polar molecules, in particular—cannot (Figure 4.16). When a lipid bilayer separates two fluids with differing solute concentrations, water will diffuse across it. The direction of water movement depends on the relative solute concentration of the two fluids, which we describe in terms of tonicity. If the overall solute concentrations of the two fluids differ, the fluid with the lower concentration of solutes is said to be hypotonic (hypo–, under). The other one, with the higher solute concentration, is hypertonic (hyper–, over). Water diffuses from a hypotonic fluid into a hypertonic one. The diffusion will continue until the two fluids are isotonic, which means they have the same overall solute concentration. The move- ment of water across a membrane is so important in biology that it is given a special name: osmosis (Figure 4.17).

diffusion The spontaneous spreading of molecules or atoms.

electron transfer chain series of enzymes and other molecules in a cell membrane that accept and give up electrons, thus releasing the energy of the electrons in steps.

feedback inhibition Mechanism by which a change that results from some activity decreases or stops the activity.

hypertonic Describes a fluid that has a high overall solute concentration relative to another fluid.

hypotonic Describes a fluid that has a low overall solute concentration relative to another fluid.

isotonic Describes two fluids with identical solute concentrations.

osmosis Diffusion of water across a selectively per- meable membrane; occurs when there is a difference in solute concentration between the fluids on either side of the membrane.

Figure 4.16 Selective permeability of lipid bilayers. Hydrophobic molecules, gases, and water molecules can cross a lipid bilayer on their own. Ions in particular and most polar organic molecules such as glucose cannot.

gresei/Shutterstock.com.

selectively permeable membrane

Figure 4.17 Osmosis. Water moves across a selectively permeable membrane that separates two fluids of differing tonicity (red dots represent solutes). The fluid volume changes in the two compartments as water diffuses across the membrane.

selectively permeable membrane

74 Unit 1 HoW CELLs WoRk

Take-Home Message 4.5 What influences the movement of ions and molecules?

• solutes tend to diffuse into an adjoining region of fluid in which they are not as con- centrated. The steepness of a concentration gradient as well as temperature, molecu- lar size, charge, and pressure affect the rate of diffusion.

• When two fluids of different solute concentration are separated by a selectively permeable membrane, water diffuses from the hypotonic to the hypertonic fluid. This movement, osmosis, is opposed by turgor.

Figure 4.18 effects of tonicity in human red blood cells. These cells have no mechanism to compensate for dif- ferences in solute concentration between cytoplasm and extracellular fluid. (A) Annie Cavanagh/Wellcome Images; (B, C) CMSP/Getty Images.

If a cell’s cytoplasm becomes hypertonic with respect to the fluid outside of its plasma membrane, water will diffuse into the cell. If the cytoplasm becomes hypo- tonic, water will diffuse out. In either case, the solute concentration of the cytoplasm may change. If it changes enough, the cell’s enzymes will stop working, with lethal results. Many cells have built-in mechanisms that compensate for differences in sol- ute concentration between cytoplasm and extracellular (external) fluid. In cells with no such mechanism, the volume—and solute concentration—of cytoplasm changes when water diffuses into or out of the cell (Figure 4.18).

The rigid cell walls of plants and many protists, fungi, and bacteria can resist an increase in the volume of cytoplasm even in hypotonic environments. In the case of plant cells, cytoplasm usually contains more solutes than soil water does. Thus, water usually diffuses from soil into a plant—but only up to a point. Stiff walls keep plant cells from expanding very much, so an inflow of water causes pressure to build up inside them. Pressure that a fluid exerts against a structure that contains it is called turgor. When enough pressure builds up inside a plant cell, water stops diffusing into its cytoplasm. The amount of turgor that is enough to stop osmosis is called osmotic pressure.

Osmotic pressure keeps walled cells plump, just as high air pressure inside a tire keeps it inflated. A young land plant can resist gravity to stay erect because its cells are plump with cytoplasm (Figure 4.19A). When soil dries out, it loses water, so the concentration of solutes increases in it. If soil water becomes hypertonic with respect to cytoplasm, water will start diffusing out of the plant’s cells, causing their cyto- plasm to shrink (Figure 4.19B). As turgor inside the cells decreases, the plant wilts.

A. Red blood cells in an isotonic solution (such as the fluid portion of blood) have a normal, indented disk shape.

B. Water diffuses out of red blood cells immersed in a hypertonic solution, so they shrivel up.

C. Water diffuses into red blood cells immersed in a hypotonic solution, so they swell up. some of these have burst.

2 µm

Figure 4.19 turgor, as illustrated in cells of iris petals. (A,B) Perennou Nuridsany/Science Source; (inset) © Evgenyi/Shutterstock.com.

A. osmotic pressure keeps plant parts erect. These cells in an iris petal are plump with cytoplasm.

B. Cells from a wilted iris petal. The cytoplasm shrank, and the plasma membrane is pulled away from the cell wall.

ENERgy AND METAboLIsM ChApter 4 75

facilitated diffusion Passive transport mechanism in which a solute follows its concentration gradient across a membrane by moving through a transport protein.

passive transport Membrane-crossing mechanism that requires no energy input.

turgor Pressure that a fluid exerts against a mem- brane, wall, or other structure that contains it.

4.6 Membrane Transport Mechanisms reMeMBer: Phospholipids swirled into water will spontaneously organize themselves into lipid bilayer sheets or bubbles; a transport protein moves specific solutes across a cell membrane (section 3.3). some cells use pseudopods to engulf a target (3.5).

Substances that do not diffuse directly through lipid bilayers can cross a cell mem- brane through transport proteins embedded in it. Each type of transport protein allows a specific substance to cross: Calcium pumps pump only calcium ions; glu- cose transporters transport only glucose; and so on. This specificity is an important part of homeostasis. Consider how the composition of cytoplasm depends on move- ment of particular solutes across the plasma membrane, which in turn depends on the transporters in it. Glucose is an important source of energy for most cells, so they normally take up as much as they can from extracellular fluid. They do so with the help of glucose transporters in the plasma membrane. As soon as a molecule of glucose enters cytoplasm, an enzyme (hexokinase, shown in Figure 4.8) phosphory- lates it. Phosphorylation traps the molecule in the cell because the transporters are specific for glucose, not phosphorylated glucose. Thus, phosphorylation prevents the molecule from moving back through the transport protein and leaving the cell.

Passive Transport Osmosis is an example of passive transport, a membrane- crossing mechanism that requires no energy input. The diffusion of solutes through transport proteins is another example. In this case, the movement of the solute (and the direction of its movement) is driven entirely by the solute’s concentration gradi- ent. Some transport proteins form pores: permanently open channels through a membrane. Other channels are gated, which means they open and close in response to a stimulus such as a shift in electric charge or binding to a signaling molecule. With a passive transport mechanism called facilitated diffusion, a solute binds to a transport protein, which then changes shape so the solute is released to the other side of the membrane. A glucose transporter is an example of a transport protein that works in facilitated diffusion (Figure 4.20). This protein changes shape when it binds to a molecule of glucose. The shape change moves the glucose to the oppo- site side of the membrane, where it detaches from the transport protein. Then, the glucose transporter reverts to its original shape.

Figure 4.20 An example of facilitated diffusion.

A. A glucose molecule (here, in extracellular fluid) binds to a glucose transporter (gray) in the plasma membrane.

B. binding causes the transport protein to change shape.

C. The transport protein releases the glucose on the other side of the membrane (in cytoplasm) and resumes its original shape.

Extracellular Fluid

Cytoplasm

glucose

Figure it Out: In this example, which fluid is hypo- tonic: extracellular fluid or cytoplasm?

Answer: Cytoplasm

76 Unit 1 HoW CELLs WoRk

Active Transport Maintaining a solute’s concentration often means transporting the solute against its gradient, to the side of the membrane where it is more con- centrated. This takes energy. In active transport, a transport protein uses energy to pump a solute against its gradient across a cell membrane. Typically, an energy input (for example, in the form of a phosphate-group transfer from ATP) changes the shape of the transport protein. The shape change causes the protein to release a bound solute to the other side of the membrane.

A calcium pump moves calcium ions across cell mem- branes by active transport (Figure 4.21). Calcium ions act as potent messengers inside cells, and they also affect the activ- ity of many enzymes. Thus, their concentration in cytoplasm is tightly regulated. Calcium pumps in the plasma mem- brane of all eukaryotic cells can keep the concentration of calcium ions in cytoplasm thousands of times lower than it is in extracellular fluid. Another example of active transport involves sodium–potassium pumps (Figure 4.22). Nearly all cells in your body have these transport proteins.

Bear in mind that the membranes of all cells, not just those of animals, have proteins that carry out active trans- port. In plants, for example, transport proteins in the plasma membranes of photosynthetic cells pump sucrose from cyto- plasm into tubes that thread throughout the plant body.

Membrane Trafficking Vesicles are constantly carrying materials to and from a cell’s plasma membrane (Figure 4.23). Cells use vesicles to take in or expel materi- als in bulk (as opposed to one molecule or ion at a time via transport proteins). A cell can expel bulk materials by exocytosis, a pathway in which a vesicle in the cytoplasm moves to the cell’s surface

and fuses with the plasma membrane 2

. As the exocytic vesicle loses its identity, its contents are released to extracellular fluid 3

. The cell can take in bulk materials by endocytosis. In one endocytic pathway, a small patch of plasma membrane balloons into the cytoplasm, bringing with it a drop of extracellular fluid (along with solutes and particles suspended in it). As the balloon sinks into the cytoplasm, the hydrophobic tails of the lipids in the bilayer are repelled by the watery fluid on both sides. The fluid “pushes” the phos- pholipid tails together, which helps round off the bud as a vesicle.

Figure 4.21 Active transport of calcium ions.

ATP ADP + Pi

Ca+ Ca+

Ca+

A. Two calcium ions (blue) bind to the transport protein (a calcium pump, gray).

ATP ADP + Pi

Ca+ Ca+

Ca+

B. A phosphate group from ATP causes the protein to change shape so that the calcium ions are ejected to the opposite side of the membrane.

ATP ADP + Pi

Ca+ Ca+

Ca+

C. After it loses the calcium ions, the transport protein resumes its original shape.

Extracellular Fluid

Cytoplasm

K+

K+ Na+

Na+

P P

Na+

Na+ ATP ADP

Extracellular Fluid

Cytoplasm

Figure 4.22 the sodium–potassium pump. This protein (gray) actively transports sodium ions (Na+) from cytoplasm to extracellular fluid, and potassium ions (k+) in the other direction. The transfer of a phosphate group ( P ) from ATP provides energy required for trans- porting both ions against their concentration gradient.

ENERgy AND METAboLIsM ChApter 4 77

Take-Home Message 4.6 how do substances and particles that cannot diffuse through lipid bilayers cross cell membranes?

• Transport proteins allow specific ions or molecules to cross a cell membrane. The types and amounts of substances that cross a membrane depend on the transport proteins embedded in it.

• In facilitated diffusion (a type of passive transport), a solute binds to a transport protein that releases it on the opposite side of the membrane. The movement is driven by the solute’s concentration gradient.

• In active transport, a transport protein pumps a solute across a membrane against its concentration gradient. The movement requires energy, as from ATP.

• Exocytosis and endocytosis move materials in bulk across a plasma membrane. some cells can engulf large particles by phagocytosis.

active transport Energy-requiring mechanism in which a transport protein pumps a solute across a cell membrane against the solute’s concentration gradient.

endocytosis Process by which a cell takes in a small amount of extracellular fluid (and its contents) by the ballooning inward of the plasma membrane.

exocytosis Process by which a cell expels a vesicle’s contents to extracellular fluid.

phagocytosis “Cell eating”; an endocytic pathway by which a cell engulfs large particles such as microbes or cellular debris.

Phagocytosis (which means “cell eating”) is a type of endocytosis in which motile cells engulf microorganisms, cellular debris, or other large particles. Many

single-celled protists such as amoebas feed by phagocytosis. Some of your white blood cells use the pathway to engulf viruses and bacteria, cancerous body cells, and other threats to health. (The micrograph on the left shows a phagocytic white blood cell engulfing several tuberculo- sis bacteria, in red.) Phagocytosis begins when receptor proteins bind to a particular target. The binding causes microfilaments just under the

plasma membrane to contract. The contraction forces a lobe of membrane-enclosed cytoplasm to bulge outward as a pseudopod. Pseudopods that merge around a target trap it inside a vesicle that sinks into the cytoplasm.

Figure 4.23 Membrane crossings. A plasma membrane is a hub of activity: Molecules and ions (colored balls) are constantly flowing into and out of a cell via transport proteins embedded in its plasma membrane. Vesicles are also taking in or expelling bulk amounts of solutes and much larger particles.

Exocytosis begins as a vesicle moves to the plasma membrane.

The vesicle’s membrane fuses with the plasma membrane.

As the membranes fuse, the vesicle’s contents are released to the extracellular fluid.

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Summary Section 4.1 Currently the most serious drug problem on college campuses is binge drinking. drinking more alcohol than the body’s enzymes can detoxify damages the body, and it can be lethal in the short term or the long term.

Section 4.2 Energy is the capacity to do work. Energy cannot be created or destroyed (first law of thermodynamics), but it can be converted from one form to another and transferred between objects or systems. Energy tends to disperse spontaneously

(second law of thermodynamics). a bit disperses at each energy transfer, usually in the form of heat.

living things maintain their organization only as long as they harvest energy from someplace else. Energy flows in one direction through the biosphere, starting mainly from the sun, then into and out of ecosystems. Producers and then consumers use the captured energy to assemble, rearrange, and break down organic molecules that cycle among organisms in an ecosystem.

Section 4.3 Cells store and retrieve energy by making and breaking chemical bonds in chemical reactions, in which reactants are con verted to products. some reactions require a net energy input; others end with a net energy release. Activation energy is the minimum

energy input required to start a reaction.

Section 4.4 Enzymes greatly enhance the rate of reactions without being changed by them. Each has an active site that is complementary in shape, size, polarity, and charge to the enzyme’s

substrate, and each works best within a characteristic range of conditions, including temperature, salt concentration, and pH. Most enzymes require assistance from cofactors; organic cofactors are coenzymes. atP is often used as a coenzyme to carry energy between reactions. When a phosphate group is transferred from atP to another molecule, energy is transferred along with it. Phosphate-group transfers (phosphorylations) to and from atP couple reactions that release energy with reactions that require energy.

Metabolic pathways are sequences of enzyme- mediated reactions that build, convert, and break down organic molecules. regulating metabolic pathways allows cells to conserve energy and resources by making only what they need at a given time. the activity of many enzymes can be regulated, for example by binding of a regulatory molecule. the products of some metabolic pathways inhibit their own production, a regulatory

mechanism called feedback inhibition. Electron transfer chains allow cells to harvest energy in small, manageable steps.

Section 4.5 the rate of diffusion is influenced by temperature, solute size, and regional differences in concentration, charge, and pressure. gases, water, and nonpolar molecules can diffuse directly through a lipid bilayer. ions and most polar molecules cannot.

Osmosis is the diffusion of water across a selectively permeable membrane, from a hypotonic fluid toward a hypertonic fluid. there is no net movement of water between isotonic solutions. osmotic pressure is the amount of turgor (fluid pressure against a cell membrane or wall) sufficient to halt osmosis.

Section 4.6 ions and most polar molecules can cross cell membranes only with the help of a transport protein. With facilitated diffusion, a solute follows its concentration gradient across a membrane through a transport protein. Facilitated diffusion is a type

of passive transport (no energy input is required). With active transport, a transport protein uses energy to pump a solute across a membrane against its concentration gradient. a phosphate-group transfer from atP often supplies energy needed for active transport.

Particles and substances in bulk and large particles are moved across plasma membranes by exocytosis and endocytosis. in exocytosis, a cytoplasmic vesicle fuses with the plasma membrane, and its contents are released to the outside of the cell. in one endocytic pathway, a patch of plasma membrane balloons into the cell, taking with it a drop of extracellular fluid (along with solutes and particles in it). the balloon forms a vesicle that sinks into the cytoplasm. some cells can engulf large particles such as other cells by the endocytic pathway of phagocytosis.

ATP

Answers in Appendix i

1. is life’s primary source of energy. a. Food c. sunlight b. Water d. atP

2. Which of the following statements is not correct? a. Energy cannot be created or destroyed. b. Energy cannot change from one form to another. c. Energy tends to disperse spontaneously.

self-Quiz

ENERgy AND METAboLIsM ChApter 4 79

1. beginning physics students are often taught the basic concepts of thermodynamics with two phrases: First, you can never win. second, you can never break even. Explain.

2. Water molecules tend to diffuse in response to their own concentration gradient. How can water be more or less concentrated?

3. dixie bee wanted to make JEll-o shots for her next party, but felt guilty about encouraging her guests to consume alcohol. she tried to compensate for the toxicity of the alcohol by adding pieces of healthy fresh pineapple to the shots, but when she did, the JEll-o never solidified. What happened? Hint: JEll-o is mainly sugar and a gelatinous mixture of proteins.

4. the enzyme trypsin is sold as a dietary enzyme supplement. Explain what happens to trypsin taken with food.

5. the enzyme catalase combines two hydrogen peroxide mol- ecules (H

2o2 + H2o2) to make two molecules of water (2H2o). a gas also forms. What is the gas?

3. if we liken a reaction to an energy hill, then a reaction that is an uphill run. a. requires energy b. releases energy c. runs from reactants to products d. uses an enzyme and a cofactor

4. in an energy-requiring reaction, activation energy is a bit like . a. a burst of speed b. coasting downhill c. a bump at the top of the hill d. putting on the brakes

5. are always changed by participating in a reaction. (Choose all that are correct.) a. Enzymes c. reactants b. Cofactors d. Coenzymes

6. an environmental factor that directly influences enzyme function is . a. temperature c. light b. wind d. all of the above

7. a metabolic pathway . a. may build or break down molecules b. generates heat c. can include an electron transfer chain d. all of the above

8. Which of the following statements is not correct? a. some metabolic pathways are cyclic. b. glucose can diffuse directly through a lipid bilayer. c. Feedback inhibition controls some metabolic pathways. d. all coenzymes are cofactors. e. osmosis is a case of diffusion.

9. ions or molecules tend to diffuse from a region where they are (more/less) concentrated to another where they are (more/less) concentrated.

10. cannot diffuse directly across a lipid bilayer. a. Water c. ions b. gases d. all of the above

11. if you immerse a human red blood cell in a hypotonic solution, water will . a. diffuse into the cell c. show no net movement b. diffuse out of the cell d. move in by endocytosis

12. Fluid pressure against a wall or cell membrane is called . a. osmosis c. diffusion b. turgor d. osmotic pressure

13. a transport protein requires atP to pump sodium ions across a membrane. this is a case of . a. passive transport c. facilitated diffusion b. active transport d. a and c

14. Vesicles are part of . a. endocytosis c. phagocytosis b. exocytosis d. all of the above

15. Match each term with its most suitable description. reactant a. assists enzymes phagocytosis b. forms at reaction’s end first law c. enters a reaction of thermodynamics d. requires energy input product e. one cell “eats” another cofactor f. energy cannot be created concentration gradient or destroyed passive transport g. basis of diffusion active transport h. no energy input required atP i. goes in circles cyclic pathway j. currency in a cell’s energy economy

Critical thinking

5.1 A Burning Concern 82

5.2 To Catch a Rainbow 83

5.3 Light-Dependent Reactions 85

5.4 Light-Independent Reactions 87

5.5 A Global Connection 89

5.6 Fermentation 92

5.7 Food as a Source of Energy 94

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Figure 5.1 Worldwide, most air pollution comes from burning fossil fuels. (A) ChinaFotoPress/Getty Images; (B) www.photo.antarctica.ac.uk.

Application

B. Air bubbles trapped in Antarctic ice core slices such as this one are samples of Earth’s atmosphere as it was when the ice formed. The deeper the slice, the older the air in the bubbles. From the deepest samples, we know that the level of carbon dioxide in the atmosphere is now higher than it has been for at least 15 million years.

A. Air pollution—smog—blankets Lianyungang, China, in December 2013. The brown color of smog comes from one of its components, a gas (nitric oxide) that is toxic in large amounts. Invisible components include other nitro- gen compounds, sulfur compounds, organic molecules, mercury and other heavy metals, and carbon dioxide.

5.1 A Burning Concern REMEMBER: Producers make their own food; consumers ingest tissues of other organisms (Section 1.3). Photosynthesis is the metabolic pathway (4.4) by which plants and other producers harness the energy (4.2, 4.3) in light to make sugars (2.7).

Your body is about 9.5 percent carbon by weight, which means that you contain an enormous number of carbon atoms. Where did they all come from? Those atoms may have passed through other consumers before you ate them, but at some point they were components of producers. The vast majority of producers get their carbon from carbon dioxide (CO2), a gas in air. Your carbon atoms—and those of most other organisms on land—were recently part of Earth’s atmosphere, in molecules of CO2.

The main producers in the human food chain are plants. Plants make their own food by photosynthesis, a pathway that harnesses the energy of sunlight to drive the assembly of sugars from carbon dioxide and water. Photosynthesis removes carbon dioxide from the atmosphere, and fixes its carbon atoms in organic compounds. When plants and other organisms break down organic compounds for energy, car- bon atoms are released in the form of CO2, which then reenters the atmosphere. For billions of years, these two processes have constituted a more or less balanced cycle of the biosphere (you will learn more about the carbon cycle in Section 17.6). For now, know that the amount of carbon dioxide that photosynthesis removes from the atmosphere is roughly the same amount that organisms release back into it—at least it was, until humans came along. As early as 8,000 years ago, humans began burn- ing forests to clear land for agriculture. When trees and other plants burn, most of the carbon in their tissues is released into the atmosphere as CO2. Fires that occur naturally release carbon dioxide the same way.

Today, we burn a lot more than our ancestors ever did. In addition to wood, we are burning fossil fuels—coal, petroleum, and natural gas—to satisfy our greater and greater demands for energy. Fossil fuels are the organic remains of ancient organ- isms. When we burn fossil fuels, we release the carbon that has been locked in their organic molecules for hundreds of millions of years, mainly as carbon dioxide that reenters the atmosphere.

Our extensive use of fossil fuels has put Earth’s atmospheric cycle of carbon dioxide out of balance: We are adding far more CO2 to the atmosphere than pho- tosynthetic organisms are removing from it, and the excess is fueling global climate change (we return to this topic in Section 18.5). In 2013 alone, humans released over 36 billion tons of CO2 into the atmosphere—an increase of 61 percent over 1990 and twice as much as photosynthesis removed from the atmosphere during the same year. Most of the CO2 that humans release comes from burning fossil fuels (Figure 5.1A). How do we know? Researchers can determine how long ago the carbon atoms in a sample of CO2 were part of a living organism by measuring the ratio of different carbon isotopes in it (you will read more about radioisotope dating techniques in Section 11.4). The results are correlated with global statistics on fossil fuel extraction, refining, and trade.

Tiny pockets of Earth’s ancient atmosphere remain in Antarctica, preserved in snow and ice that have been accumulating in layers, year after year, for millions of years (Figure 5.1B). Air and dust trapped in each layer reveal the composition of the atmosphere that prevailed when the layer formed. These layers tell us that the atmo- spheric CO2 level was relatively stable for about 10,000 years before the industrial revolution began in the mid-1800s. Since then, the CO2 level has been steadily ris- ing. Today, the atmospheric CO2 level is higher than it has been for 15 million years.

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pigment An organic molecule that can absorb light of certain wavelengths.

wavelength Distance between the crests of two suc- cessive waves.

Figure 5.2 properties of light. Electromagnetic radiation moves through space in waves that we measure in nanometers (nm). Visible light makes up a very small part of this energy. Raindrops or a prism can separate visible light’s different wavelengths, which we see as different colors. About 25 million nanometers are equal to 1 inch. Left, © Robbie George, National Geographic Creative.

5.2 To Catch a Rainbow REMEMBER: An electron that absorbs energy moves to a higher energy level, then emits the extra energy and moves back down (Section 2.2). Chloroplasts are organ- elles specialized for photosynthesis (3.5). Sustaining life’s organization requires ongoing energy inputs to counter energy loss (4.2). Building, rearranging, or break- ing down an organic substance often occurs stepwise, in a series of enzymatic reac- tions called a metabolic pathway (4.4).

Energy flow through nearly all ecosystems on Earth begins when photosynthesizers capture the energy in sunlight. Harnessing that energy is a complicated business; plants do it by converting it to chemical energy, which they and most other organ- isms use to drive cellular work. Understanding the conversion process requires a bit of knowledge about the nature of light.

Light is electromagnetic radiation, a type of energy that moves through space in waves, a bit like waves move across an ocean. The distance between the crests of two successive waves is called wavelength, and it is measured in nanometers (nm). Light that is visible to the human eye is only a tiny part of the spectrum of elec- tromagnetic radiation emitted by the sun (Figure 5.2). This visible light travels in wavelengths between 380 and 750 nm, and it is the main form of energy that drives photosynthesis. Our eyes perceive all of these wavelengths combined as white light, and particular wavelengths in this range as different colors. White light separates into its component colors when it passes through a prism, or raindrops that act as tiny prisms. A prism bends longer wavelengths more than it bends shorter ones, so a rainbow of colors forms.

Photosynthesizers use pigments to capture the energy of visible light. A pig- ment is an organic molecule that selectively absorbs light of certain wavelengths, a bit like an antenna specialized for receiving light energy. Absorbing energy of the appropriate wavelength excites a pigment’s electrons. An excited electron (one that has been boosted to a higher energy level) quickly emits its extra energy and returns to a lower energy level. As you will see, photosynthetic cells can capture energy emitted from an electron returning to a lower energy level.

shortest wavelengths (highest energy)

visible light

longest wavelengths (lowest energy)

gamma rays ultravioletx-rays near-infrared infrared microwaves radio waves

400 nm 500 nm 600 nm 700 nm

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Figure 5.3 A few photosynthetic pigments. The curves in this graph show the efficiency at which each pigment absorbs the different wavelengths of visible light. Line color indicates the pigment’s characteristic color. using a combination of pigments allows photosyn- thetic organisms to maximize the range of wavelengths they can capture for photosynthesis. Top, © Photobac/Shutterstock.

All life is sustained by inputs of energy, but not all forms of energy can sustain life.

Wavelengths of light that are not absorbed by a pigment are reflected, and that reflected light gives each pigment its characteristic color. Chlorophyll a is the most common photosynthetic pigment in plants and photosynthetic protists. It also occurs in some bacteria. Chlorophyll a absorbs violet, red, and orange light, and it reflects green light, so it appears green to us. Accessory pigments, including other chlorophylls, collectively harvest a wide range of additional light wavelengths for photosynthesis and for other purposes. Many accessory pigments protect cells from the damaging effects of ultraviolet (UV) light in the sun’s rays. Appealing colors attract animals to ripening fruit or pollinators to flowers. You may already be familiar with some of these molecules: Carrots, for example, are orange because they contain beta-carotene (which is often abbreviated as β-carotene); roses are red and violets are blue because their cells make anthocyanins.

Most photosynthetic organisms maximize the range of wavelengths they can capture for photosynthesis by using a combination of pigments (Figure 5.3). In green plants, chlorophylls are usually so abundant that they mask the colors of the other pigments. Plants that change color during autumn are preparing for a period of dormancy; they conserve resources by moving nutrients from tender parts that would be damaged by winter cold (such as leaves) to protected parts (such as roots). Chlorophylls are not needed during dormancy, so they are disassembled and their components recycled. Yellow and orange accessory pigments are also recycled, but not as quickly as chlorophylls. Their colors begin to show as the chlorophyll content declines in leaves. Anthocyanin synthesis also increases in some plants, adding red and purple tones to turning leaf colors.

Storing Energy in Sugars All life is sustained by inputs of energy, but not all forms of energy can sustain life. Sunlight, for example, is abundant here on Earth, but it cannot be used to directly power protein synthesis or other energy-requiring reactions that all organisms must run in order to stay alive. Photosynthesis converts the energy of light into the energy of chemical bonds. Unlike light, chemical energy can power the reactions of life, and it can be stored for later use.

In plants and other photosynthetic eukaryotes, photosynthesis takes place in chloroplasts (Figure 5.4A). Plant chloroplasts have two outer membranes, and they are filled with a thick, cytoplasm-like fluid called stroma (Figure 5.4B). Suspended in the stroma are the chloroplast’s own DNA, some ribosomes, and an inner, much- folded thylakoid membrane. The folds of a thylakoid membrane typically form stacks of interconnected disks called thylakoids. The space enclosed by the thyla- koid membrane is a single, continuous compartment (Figure 5.4C).

Photosynthesis is often summarized by an equation:

C6H12O6 � �6O2 6H2O 36 ATP36 ADP 6CO2 � �

sugar oxygen carbon dioxide water

�� sugars O2CO2 water light energy

This equation means that photosynthesis converts CO2 and water to sugars and oxygen. However, photosynthesis is not a single reaction. Rather, it is a metabolic pathway with many reactions that occur in two stages. Molecules in the thylakoid membrane carry out the reactions of the first stage, which are driven by light and thus called the light-dependent reactions. The “photo” in photosynthesis means light, and it refers to the conversion of light energy to chemical bond energy of ATP during this stage. In addition to making ATP, the main light-dependent pathway in chloro- plasts splits water molecules and releases O2. Hydrogen ions and electrons from the water molecules end up in the coenzyme NADPH (Figure 5.5A).

The “synthesis” part of photosynthesis refers to the reactions of the second stage, which build sugars from CO2 and water. These sugar-building reactions run

phycoerythrobilin phycocyanobilin

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5.3 Light-Dependent Reactions REMEMBER: Successively higher electron energy levels can be represented as nested shells (Section 2.2). Potential energy is stored in the position or arrangement of objects in a system (4.2). Electron transfer chains can harvest the energy of elec- trons in small, usable increments; phosphorylation is a reaction in which a phosphate group is transferred from one molecule to another (4.4). Ions and other substances that do not diffuse directly through lipid bilayers can cross a cell membrane through transport proteins embedded in it; in active transport, a transport protein uses energy to pump a solute against its gradient across a cell membrane (4.6).

When a chlorophyll or accessory pigment absorbs light, one of its electrons jumps to a higher energy level (shell). The electron quickly drops back down to a lower shell by emitting its extra energy. In the thylakoid membrane, energy emitted by an electron is not lost to the environment. In this special membrane, photosynthetic pigments occur in clusters held together by proteins. These clusters can hold onto energy by passing it back and forth, a bit like volleyball players pass a ball among team members.

Take-Home Message 5.2 how do cells harvest light for photosynthesis?

• The sun emits light, which travels in waves. we see different wavelengths of visible light as different colors.

• Visible light is the main form of energy that drives photosynthesis. Photosynthetic species use pigments such as chlorophyll a to harvest this energy for photosynthesis.

• In eukaryotic cells, the first stage of photosynthesis occurs at the thylakoid membrane of chloroplasts. During these light-dependent reactions, light energy drives the forma- tion of ATP and nADPH.

• The second stage occurs in the stroma. During these light-independent reactions, ATP and nADPH drive the synthesis of sugars from water and carbon dioxide.

chlorophyll a Main photosynthetic pigment in plants. stroma The cytoplasm-like fluid between the thyla- koid membrane and the two outer membranes of a chloroplast.

thylakoid membrane A chloroplast’s highly folded inner membrane system; forms a continuous compartment.

Figure 5.5 inputs and outputs of the two stages of photosynthesis.

Figure 5.4 Zooming in on a chloroplast. The first stage of photosynthesis takes place at the thyla- koid membrane; the second stage runs in the stroma. (A) Michael Eichelberger/Visuals Unlimited.

in the stroma. They are collectively called the light-independent reactions because light energy does not power them. Instead, they run on energy delivered by NADPH and ATP that formed during the first stage (Figure 5.5B).

ATP

NADPH

ADP

energy

NADP+ H2O

ADP

NADP+

sugars

ATP

H2O

NADPH CO2

A. Chloroplasts in leaf cells of a moss. B. Three membranes of a chloroplast. C. Part of the thylakoid membrane, cutaway view.

A. Light-dependent reactions of photosynthesis

B. Light-independent reactions of photosynthesis (Calvin–Benson cycle)

The reactions of photosynthesis begin when energy being passed around the thylakoid membrane reaches and becomes absorbed by a photosystem (Figure 5.6). A photosystem is a grouping of hundreds of chlorophylls, accessory pigments, and other molecules. When a photosystem absorbs light energy

, it releases electrons that immediately enter an electron transfer chain in the thylakoid membrane. (With this step, light energy has been converted to chemical energy.) The photosystem must replace its lost electrons, and it does so by pulling them off of water molecules in the thylakoid compartment. Water molecules do not give up electrons very easily; doing so causes them to break apart into hydrogen ions and oxygen atoms

. The hydrogen ions remain in the thylakoid compartment; oxygen atoms combine and diffuse out of the cell as oxygen gas (O2).

Meanwhile, the electrons released by the photosystem have been moving through the electron transfer chain

. As the electrons pass from one molecule in the chain to the next, they release a bit of their extra energy. Molecules of the chain use the released energy to actively transport hydrogen ions (H+) across the membrane, from the stroma into the thylakoid compartment

. Thus, the flow of electrons through the electron transfer chain sets up and maintains a hydrogen ion gradient across the thylakoid membrane.

At the end of the electron transfer chain, electrons are accepted by a second photosystem. When this photosystem absorbs light energy, it releases electrons

. These electrons immediately enter a second, different electron transfer chain. At the end of this chain, the coenzyme NADP+ accepts the electrons along with H+, so NADPH forms

The hydrogen ion gradient that forms across the thylakoid membrane is a type of potential energy that can be tapped to make ATP. The H+ ions want to follow their concentration gradient by moving back into the stroma, but ions cannot diffuse

A photosystem absorbs light energy and releases electrons.

The photosystem pulls replacement electrons from water molecules, which then break apart into oxygen atoms and hydrogen ions. The oxygen atoms leave the cell as O2 gas.

The electrons enter an electron trans- fer chain in the thylakoid membrane.

Energy lost by the electrons as they move through the chain is used to actively transport hydrogen ions from the stroma into the thylakoid compart- ment. A hydrogen ion gradient forms across the thylakoid membrane.

Hydrogen ions in the thyla- koid compartment follow their gradient across the thylakoid membrane by flowing through the interior of ATP synth ases.

Hydrogen ion flow causes ATP synth ases to phosphorylate ADP, so ATP forms in the stroma.

Another photosystem absorbs light energy and releases electrons. Replacement electrons come from the first electron transfer chain.

The released electrons move through a second electron transfer chain, then combine with nADP+ and H+, so nADPH forms.

Figure 5.6 Light-dependent reactions in the thylakoid membrane of chloroplasts. ATP and oxygen gas are produced in this pathway. Elec- trons that travel through two different electron transfer chains end up in nADPH, which delivers them to sugar- building reactions in the stroma.

Calvin–Benson cycle Light-independent reactions of photosynthesis; cyclic carbon-fixing pathway that forms sugars from CO2.

carbon fixation Process by which carbon from an inorganic source such as carbon dioxide gets incor- porated (fixed) into an organic molecule.

electron transfer phosphorylation Process in which electron flow through electron transfer chains sets up a hydrogen ion gradient that drives ATP formation.

NADPH

electron transfer chain electron transfer chain

e– e–

e–

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light energy light energy

ATP synthasephotosystem II photosystem I

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Capturing and releasing energy Chapter 5 87

sugars

CO2

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ATP

5.4 Light-Independent Reactions reMeMBer: plant cells store sugars in the form of starch, a polymer of glucose (section 2.7). a plant cuticle helps stems and leaves retain water (3.5). an active site is a pocket in an enzyme where substrates bind and a reaction occurs (4.4).

Energy that drives the second stage of photosynthesis is provided not by light; rather, the reactions run on the energy of electrons delivered by NADPH and phosphate-group transfers from ATP. These light-independent reactions, which are collectively called the Calvin–Benson cycle, produce sugars in the stroma of chloroplasts (Figure 5.7). This cyclic pathway uses carbon atoms from CO2 to build the carbon backbones of the sugar molecules. Extracting carbon atoms from an inorganic source (such as CO2) and incorporating them into an organic molecule is a process called carbon fixation.

In most plants, photosynthetic protists, and some bacteria, the enzyme rubisco fixes carbon by attaching CO2 to a five-carbon compound called RuBP. The six-carbon intermediate that forms by this reaction is unstable, so it splits right away into two three-carbon molecules of PGA, which continue in the cycle. NADPH and ATP are used to convert these molecules to sugars.

It takes six cycles of Calvin–Benson reactions to fix the six carbon atoms necessary to make one molecule of glucose (a six-carbon sugar). Plant cells break down some of the glucose they make to access the energy stored in its bonds. However, most of the glucose they make is converted at once to sucrose or starch by other pathways that conclude the light-independent reactions. Excess glucose is stored as starch grains in chloroplast stroma. When sugars are needed in other parts of the plant, the starch is broken apart into its glucose monomers.

Alternative Carbon-Fixing Pathways The aboveground parts of most plants are covered with a cuticle that limits evaporative water loss. Gases cannot diffuse across the cuticle, but oxygen produced by the light-dependent reactions must escape

Take-Home Message 5.3 What happens during the first stage of photosynthesis?

• photosynthetic pigments in the thylakoid membrane transfer the energy of light to photosystems, which release electrons that enter electron transfer chains.

• the flow of electrons through electron transfer chains sets up a hydrogen ion gradient that drives atp formation.

• Water molecules are split, oxygen is released, and electrons end up in nadpH.

through the lipid bilayer. H+ leaves the thylakoid compartment only by flowing through proteins called ATP synthases embedded in the thylakoid membrane

. An ATP synthase is both a transport protein and an enzyme. When hydrogen ions flow through its interior, the protein phosphorylates ADP, so ATP forms in the stroma

. The process by which the flow of electrons through electron transfer chains drives ATP formation is called electron transfer phosphorylation.

Figure 5.7 the Calvin–Benson cycle. this sketch shows a cross-section of a chloroplast with the reactions cycling in the stroma. six cycles of the Calvin–Benson reactions produce one six-carbon sugar.

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Take-Home Message 5.4 What happens during the second stage of photosynthesis?

• During the light-independent reactions (the second stage of photosynthesis), ATP and nADPH drive the synthesis of sugars from CO2.

• when stomata close on hot, dry days, they also prevent the exchange of gases between plant tissues and the air. This outcome reduces the efficiency of sugar pro- duction in C3 plants.

• Plants adapted to hot, dry conditions fix carbon twice. C4 plants separate the two sets of reactions in space; CAM plants separate them in time.

Figure 5.9 C4 and CAM plants. (A) Image courtesy msuturfweeds.net; (B) © Tamara Kulikova/Shutterstock.

Figure 5.8 Stomata on the surface of a leaf. when these tiny pores are open, gases can be exchanged between the plant’s internal tissues and air. Gas exchange ends when stomata close to conserve water on dry days. © D. Kucharski & K. Kucharska/Shutterstock.

A. Crabgrass “weeds” overgrowing a lawn. Crabgrasses, which are C4 plants, thrive in hot, dry summers, easily outcompeting kentucky bluegrass and other fine-leaved C3 grasses commonly planted in residential lawns.

B. The jade plant, Crassula argentea, and other CAM plants survive in hot deserts by opening stomata to fix carbon only at night. They run the Calvin–Benson cycle during the day, with stomata closed.

the plant, and carbon dioxide needed for the Calvin–Benson cycle must enter it. Thus, most leaves and stems are studded with tiny, closable gaps called stomata (singular, stoma; Figure 5.8). When stomata are open, CO2 diffuses from air into photosynthetic tissues, and O2 diffuses out of the tissues into air. Stomata close to conserve water on hot, dry days. When that happens, gas exchange comes to a halt.

Both stages of photosynthesis run during the day. With stomata closed, the O2 level in the plant’s tissues rises, and the CO2 level declines. This outcome can reduce the efficiency of sugar production because both gases are substrates of rubisco, and they compete for its active site. Rubisco starts the Calvin–Benson cycle by attaching CO2 to RuBP. It also attaches O2 to RuBP. To convert the product of this alternate reaction to a substrate of the Calvin–Benson cycle, the cell uses additional ATP and NADPH, and it also loses carbon in the form of CO2. The detrimental effects of the alternate pathway are greatest in C3 plants, which use only the Calvin–Benson cycle to fix carbon (they are called C3 plants because a three-carbon molecule, PGA, is the first stable intermediate to form in their light-independent reactions). In a C3 plant, sugar production becomes less and less efficient as daytime temperature rises.

An additional set of carbon-fixing reactions minimizes the effects of rubisco’s inefficiency in corn, bamboo, and other C4 plants (so named because a four- carbon molecule is the first stable intermediate to form in their light-independent reactions). These plants also close stomata on dry days, but the efficiency of their sugar production does not decline. C4 plants fix carbon twice, in two kinds of cells. In the first cell, carbon is fixed by an enzyme that cannot use oxygen as a substrate. The resulting intermediate is transported to a second cell, where it is converted to CO2. There, rubisco fixes carbon for the second time as the CO2 enters the Calvin– Benson cycle. The extra C4 reactions keep the CO2 level high near rubisco, so sugar production stays efficient even during hot, dry weather (Figure 5.9A).

Succulents, cacti, and other CAM plants use a carbon-fixing pathway that allows them to produce sugar efficiently even where typical daytime conditions are extremely hot and dry. CAM stands for crassulacean acid metabolism, after the Crassulaceae family of plants in which this pathway was first studied (Figure 5.9B). Like C4 plants, CAM plants fix carbon twice, but the reactions occur at different times rather than in different cells. Stomata on a CAM plant open only at night, when typically lower temperatures minimize evaporative water loss. The plant’s cells use a C4 pathway to fix carbon from CO2 in the air at this time. The product of the pathway is stored in the cell’s central vacuole. When the stomata close the next day, the molecule moves out of the vacuole and becomes broken down to CO2. Rubisco then fixes carbon for the second time as the CO2 enters the Calvin–Benson cycle.

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5.5 A Global Connection REMEMBER: Most free radicals are dangerous to life (Section 2.2). Mitochondria make ATP by aerobic respiration (3.5). Organic molecules release energy when they combine with oxygen (4.3). Most enzymes require assistance from cofactors; coenzymes carry chemical groups, atoms, or electrons between reactions; energy given off by electrons moving through an electron transfer chain drives cellular work (4.4). Ions cross a cell membrane through transport proteins; in active transport, a transport protein uses energy to move a solute across a cell membrane (4.6).

The first cells we know of appeared on Earth about 3.4 billion years ago. Like some modern prokaryotes, these ancient organisms did not tap into sunlight; rather, they extracted the energy they needed from simple molecules such as methane and hydrogen sulfide. Both gases were plentiful in the nasty brew that was Earth’s early atmosphere (Figure 5.10). When photosynthesis evolved, sunlight offered cells that used it an essentially unlimited supply of energy, and they were very successful. Oxygen gas released from uncountable numbers of water molecules began seep- ing out of the photosynthesizers. O2 reacts easily with metals, so at first, most of it combined with metal atoms in exposed rocks. After the exposed minerals became saturated with oxygen, the gas began to accumulate in the ocean and in the atmo- sphere. From that time on, the world of life would never be the same.

Before photosynthesis evolved, molecular oxygen had been a very small compo- nent of Earth’s atmosphere. In what may have been the earliest case of catastrophic pollution, the new abundance of this gas exerted tremendous pressure on all life at the time. Why? Then, as now, enzymes that require metal cofactors were a critical part of metabolism. Oxygen reacts with metal cofactors, and free radicals form dur- ing those reactions. Free radicals damage biological molecules, so they are dangerous to life. Most cells had no way to cope with them, and so were wiped out everywhere except deep water, muddy sediments, and other anaerobic (oxygen-free) places.

By lucky circumstance, a few types of cells were already making molecules that could detoxify or prevent the formation of free radicals. Cells with these molecules were the first aerobic organisms—they could live in the presence of oxygen. As aerobic organisms evolved, their detoxifying molecules became incorporated into new metabolic pathways. One of these pathways put the reactive properties of oxy- gen to use. Today, this pathway—aerobic respiration—is the main ATP-producing sugar breakdown pathway in nearly all eukaryotes (including plants) and some modern bacteria. The pathway requires oxygen, and its products—carbon dioxide and water—are the raw materials used by the majority of photosyn- thetic organisms to build the sugars in the first place. With this connec- tion, the cycling of carbon, hydrogen, and oxygen through living things connects full circle through the bio- sphere (right).

Aerobic Respiration in Mitochondria The bonds of organic molecules hold a lot of energy that can be released in a reac- tion with oxygen. Aerobic respiration

Figure 5.10 A view of how Earth’s atmosphere was permanently changed by photosynthesis. Earth’s early atmosphere was abundant in gases such as methane, sulfur, ammonia, and chlorine. Oxygen released by early photosynthesizers changed the composition of the atmosphere. Photosynthesis is now the main path- way by which energy and carbon enter the world of life.

energy

E R O B I C R E S P I R A T

I O N

P H O T

O S Y N T H E S I S

H2O

CO2

sugar

aerobic Involving or occurring in the presence of oxygen.

aerobic respiration Oxygen-requiring metabolic path- way that breaks down sugars to produce ATP.

anaerobic Occurring in the absence of oxygen.

C3 plant Type of plant that uses only the Calvin– Benson cycle to fix carbon.

C4 plant Type of plant that fixes carbon twice, in two cell types.

CAM plant Type of plant that fixes carbon twice, at different times of day.

stomata Closable gaps on aboveground plant sur- faces. when open, they allow the plant to exchange gases with air. when closed, they limit water loss.

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ATP

ATPATP

ATP

glucose

2 pyruvate

2 acetyl–CoA

2 NADH

6 NADH 2 FADH2

4 CO2

oxygen H2O

2 CO2

(2 net)

4 2

2 NADH

Electron Transfer Phosphory lat ion

Krebs Cycle

Glycolys is

A. Stage 1 In cytoplasm, glycolysis splits a glucose molecule into 2 pyruvate; 2 nADH and 4 ATP also form. The net yield is 2 ATP.

B. Stage 2 The pyruvate enters a mitochondrion and is converted to acetyl–CoA, which enters the krebs cycle. The net yield of the sec- ond stage is 2 ATP, 8 nADH, and 2 FADH2. By the end of this stage, 6 carbon atoms have exited the cell, in 6 CO2.

C. Stage 3 In electron transfer phosphorylation, 10 nADH and 2 FADH2 donate electrons and hydrogen ions to electron transfer chains. Electron flow through the chains sets up hydrogen ion gradients that drive ATP formation. Oxygen accepts electrons at the end of the chains.

Figure 5.11 Aerobic respiration. In eukaryotes, aerobic respiration begins in cytoplasm, and ends in mitochondria.

completely breaks apart the carbon backbone of a sugar, bond by bond. Energy released as those bonds are broken drives ATP synthesis.

The reactions of aerobic respiration occur in three stages. The first stage, glycol- ysis, takes place in cytoplasm. Glycolysis is a set of reactions that convert one six- carbon sugar into two molecules of pyruvate (Figure 5.11A), an organic compound with a three-carbon backbone. The reactions occur with some variation in the cyto- plasm of almost all cells; for clarity, we focus here on those that start with glucose. Two ATP are invested to begin glycolysis, but four ATP form by the end. Thus, we say that the net (overall) yield is two ATP per glucose. Electrons and hydrogen ions released by the reactions combine with the coenzyme NAD+, so NADH also forms.

In eukaryotes, aerobic respiration continues in mitochondria. The reactions of the second stage begin when the two pyruvate molecules that formed in glycolysis enter the inner compartment of a mitochondrion (Figure 5.11B). There, each pyru- vate reacts with a coenzyme named (rather unimaginatively) coenzyme A. One mol- ecule of CO2 forms in this reaction and then diffuses out of the cell. The reaction’s

a mitochondrion

CAPTuRInG AnD RELEASInG EnERGy ChAptER 5 91

NADHNADH NADHNADH

NADH

e–

2H2O

cytoplasm

matrix

intermembrane space

cytoplasml

outer membrane

matrix

intermembrane space

inner membrane

electron transfer chain

H+ H+

H+

ATP e–e–e–e–e–e–e–e–e–

H+ H+H+H+NADH

FADH2FADH2

ADP + phosphate

NADHNADH NADHNADH

NADH

e–

2H2O

cytoplasm

matrix

intermembrane space

cytoplasml

outer membrane

matrix

intermembrane space

inner membrane

electron transfer chain

H+ H+

H+

ATP e–e–e–e–e–e–e–e–e–

H+ H+H+H+NADH

FADH2FADH2

ADP + phosphate

ATP

ATPATP

ATP

glucose

2 pyruvate

2 acetyl–CoA

2 NADH

6 NADH 2 FADH2

4 CO2

oxygen H2O

2 CO2

(2 net)

4 2

2 NADH

Electron Transfer Phosphory lat ion

Krebs Cycle

Glycolys is

glycolysis Set of reactions in which glucose is bro- ken down to two pyruvate for a net yield of two ATP.

Krebs cycle Cyclic pathway that helps break down pyruvate to carbon dioxide during aerobic respiration.

nADH and FADH2 deliver electrons and hydrogen ions to electron transfer chains in the inner mito- chondrial membrane.

Molecules of the electron transfer chain use energy released by the electrons to pump the hydrogen ions (H+) across the membrane, from the matrix to the intermembrane space. This activity sets up and maintains a hydrogen ion gradient across the inner mitochondrial membrane.

Hydrogen ion flow back to the matrix through ATP synthases drives the formation of ATP from ADP and phosphate.

Electrons at the end of the electron transfer chains combine with oxygen and hydrogen ions, so water forms.

other product, a molecule called acetyl–CoA, enters a pathway called the Krebs cycle. Each cycle of Krebs reactions releases two carbon atoms that leave the cell in molecules of CO2.

At this point in aerobic respiration, the six-carbon backbone of one glucose molecule has been broken down completely; six carbon atoms have now exited the cell in CO2. The two ATP that formed during the second stage add to the small net yield (two ATP) of glycolysis. However, six more NADH and two FADH2 (another coenzyme) also formed. Add in the two NADH from glycolysis, and the full break- down of one glucose molecule has a big potential payoff. Twelve coenzymes now deliver electrons —and the energy they carry—to the third and final stage of aerobic respiration, electron transfer phosphorylation (Figure 5.11C).

In eukaryotes, electron transfer phosphorylation occurs at the inner mitochon- drial membrane (Figure 5.12). The reactions begin when NADH and FADH2 donate their cargo of electrons and hydrogen ions to electron transfer chains embedded in this membrane

. As the electrons pass from one molecule in the chain to the next, they release a bit of their extra energy. Molecules of the chain use the released energy to actively transport hydrogen ions (H+) across the inner mitochondrial membrane, from the matrix to the intermembrane space

. Thus, the flow of electrons through the electron transfer chains sets up and maintains a hydrogen ion gradient across the membrane. This gradient attracts the ions back toward the matrix, but ions cannot diffuse through a lipid bilayer. Hydrogen ions cross the inner mitochondrial membrane only by flowing through ATP synthases embedded in the membrane. The flow of hydrogen ions through ATP synthases causes these proteins to attach phosphate groups to ADP, so ATP forms

. At the end of the electron transfer chains, oxygen accepts electrons and H+ to

form water, a product of the third-stage reactions 4

. The term aerobic respiration,

Figure 5.12 Electron transfer phosphorylation in mitochondria. In eukaryotes, the third and final stage of aerobic respiration, electron transfer phosphorylation, occurs at the inner mitochondrial membrane.

Figure 5.13 Examples of alcoholic fermentation. (A) © By London Scientific Films/Oxford Scientific/Getty Images; (B) left, © Elena Bosh- kovska/Shutterstock.com; right, optimarc/Shutterstock.com.

A. Saccharomyces cerevisiae, a yeast that carries out alcoholic fermentation.

B. Left, one product of Saccharomyces alcoholic fer- mentation (ethanol) makes beer alcoholic; another (CO2) makes it bubbly. Right, holes in bread are pockets where CO2 released by fermenting Saccharomyces cells accu- mulated in the dough.

5.6 Fermentation REMEMBER: Fungi that live as single cells are called yeasts (Section 1.4). Monomers are subunits of polymers (2.6). Sugar monomers form larger carbohydrates (2.7).

Most types of eukaryotic cells use aerobic respiration exclusively, or they use it most of the time. Many bacteria, archaea, protists, and some eukaryotic cells can harvest energy from carbohydrates by fermentation. Fermentation refers to sugar break- down pathways that produce ATP and do not require oxygen. Like aerobic respira- tion, fermentation begins with glycolysis in cytoplasm. Unlike aerobic respiration, fermentation’s concluding reactions take place in cytoplasm. Electrons do not move through electron transfer chains, so no additional ATP forms, and an organic mol- ecule (instead of oxygen) accepts electrons. In these reactions, pyruvate is converted to other molecules, but it is not fully broken down to CO2 (as occurs in aerobic respiration). The reactions remove electrons from NADH, so NAD+ forms; regener- ating this coenzyme allows glycolysis—and the ATP it offers—to continue. Thus, the net ATP yield of fermentation consists of the two ATP that form in glycolysis (see Figure 5.11A). Fermentation is inefficient compared with aerobic respiration, but it produces enough ATP to sustain many single-celled species. It also helps cells of multicelled species under anaerobic conditions.

Take-Home Message 5.5 What happens during aerobic respiration?

• Most cells can make ATP by breaking down sugars in the oxygen-requiring pathway of aerobic respiration.

• Aerobic respiration begins in cytoplasm with glycolysis, and, in eukaryotes, ends in the mitochondrion with electron transfer phosphorylation.

• A typical net yield of aerobic respiration is thirty-six ATP per glucose. Carbon dioxide and water also form.

which literally means “breathing air to live,” refers to this pathway’s requirement for oxygen as the final acceptor of electrons. Every breath you take provides your tril- lions of aerobically respiring cells with a fresh supply of oxygen.

The following equation summarizes the overall pathway of aerobic respiration:

For each glucose molecule that enters this pathway, four ATP form in the first- and second-stage reactions. Coenzymes deliver enough H+ and electrons to fuel the synthesis of about thirty-two additional ATP in the third stage. Thus, the breakdown of one glucose molecule typically yields thirty-six ATP. As you will see, other pathways that break down sugars also yield ATP, but not nearly as much as aerobic respiration. You and other large, multicelled eukaryotes could not survive without its higher efficiency.

alcoholic fermentation Anaerobic pathway that breaks down sugars and produces ATP, CO2, and ethanol.

fermentation An anaerobic pathway that breaks down sugars to produce ATP.

lactate fermentation Anaerobic pathway that breaks down sugars and produces ATP and lactate.

C6H12O6 � O2 CO2 � �H2O

glucose oxygen carbon dioxide water

ATP

Aerobic respiration literally means “breathing air to live.”

CAPTuRInG AnD RELEASInG EnERGy ChAptER 5 93

Some yeasts carry out alcoholic fermentation, a pathway that converts pyru- vate to ethanol. One yeast species, Saccharomyces cerevisiae, helps us produce beer, wine, and bread (Figure 5.13). Beer brewers often use barley that has been germi- nated and dried (a process called malting) as a source of glucose for fermentation by this yeast. As the cells make ATP for themselves, they also produce ethanol (which makes the beer alcoholic) and CO2 (which makes it bubbly). Flowers of the hop plant add flavor and help preserve the finished product. Winemakers use crushed grapes as a source of sugars for yeast fermentation. The ethanol produced by the cells makes the wine alcoholic, and the CO2 is allowed to escape to the air.

To make bread, flour is kneaded with water, yeast, and sometimes other ingre- dients. Flour contains a protein (gluten) and a sugar (maltose) that consists of two glucose subunits. Kneading causes the gluten to form polymers in long, intercon- nected strands that make the resulting dough stretchy and resilient. The yeast cells in the dough first break down the maltose, then use the released glucose for alco- holic fermentation. The CO2 they produce accumulates in bubbles that are trapped by the mesh of gluten strands. As the bubbles expand, they cause the dough to rise. The ethanol product of fermentation evaporates during baking.

In lactate fermentation, electrons and hydrogen ions carried by NADH are transferred directly to pyruvate, so NAD+ forms. This reaction converts the pyruvate to lactic acid (also called lactate). Both molecules have three carbons: No carbons are lost, so no CO2 is produced. We use lactate fermentation by beneficial bacteria to prepare many foods. Yogurt, for example, is made by allowing bacteria such as Lactobacillus bulgaricus and Streptococcus thermophilus to grow in milk (Figure 5.14A). Milk contains a disaccharide (lactose) and a protein (casein). The cells first break down the lactose into its monosaccharide subunits, then use the monosaccharides for lactate fermentation. The lactate they produce reduces the pH of the milk, which imparts tartness and causes the casein to form a gel.

Cells in animal skeletal muscles are fused as long fibers that carry out aerobic respiration, lactate fermentation, or both (Figure 5.14B). Red fibers have many mitochondria and produce ATP mainly by aerobic respiration. These fibers sustain prolonged activity. They are red because they contain myoglobin, a protein that stores oxygen for aerobic respiration. White muscle fibers contain few mitochon- dria and no myoglobin; they make most of their ATP by lactate fermentation. This pathway makes ATP quickly, so it is useful for quick, strenuous bursts of activity (Figure 5.14C). The low ATP yield does not support prolonged activity.

Most animal muscles are a mixture of white and red fibers, but the propor- tions vary. For example, great sprinters tend to have more white fibers in their leg muscles; great marathon runners have more red fibers. Chickens cannot fly far because their flight muscles consist mostly of white fibers (thus, the “white” breast meat). A chicken most often walks or runs. Its leg muscles consist mostly of red muscle fibers, the “dark meat.” Section 20.4 returns to the structure and function of skeletal muscle fibers.

Figure 5.14 Examples of lactate fermentation. (A) left, mexrix/Shutterstock.com; right SCIMAT/Science Source; (B) © William MacDonald, M.D.; (C) © Maxisport/Shutterstock.com.

B. Lactate fermentation occurs in white muscle fibers, visible in this cross-section of human thigh muscle. The red fibers, which make ATP by aerobic respiration, sustain endurance activities.

A. yogurt is a product of lactate fermentation by bacteria in milk. The micrograph shows Lactobacillus bulgaricus (red) and Streptococcus thermophilus (purple) in yogurt.

C. Intense activity such as sprinting quickly depletes oxygen in muscles. under the resulting anaerobic condi- tions, ATP is produced mainly by lactate fermentation in white muscle fibers. Fermentation does not make enough ATP to sustain this type of activity for long. Take-Home Message 5.6

What is fermentation?

• Prokaryotes and eukaryotes use fermentation pathways, which are anaerobic, to produce ATP by breaking down carbohydrates.

• Fermentation’s small ATP yield (two per molecule of glucose) occurs by glycolysis.

94 Unit 1 HOw CELLS wORk

5.7 Food as a Source of Energy REMEMBER: Animals store sugars in the form of glycogen (Section 2.7). Triglycer- ides, the main component of fats, have a glycerol head and three fatty acid tails (2.8). Proteins are polymers of amino acids (2.9).

Aerobic respiration produces a lot of ATP by fully dismantling glucose, carbon by carbon. Cells also dismantle other organic molecules to make ATP. Complex carbohydrates, fats, and proteins in food can be converted to molecules that enter glycolysis or the Krebs cycle (Figure 5.15). As in glucose metabolism, the energy of electrons that are transferred to coenzymes ultimately drives the synthesis of ATP.

Complex Carbohydrates In humans and other mammals, the digestive system breaks down starch and other complex carbohydrates to their sugar subunits, which are quickly taken up by cells for glycolysis. When a cell produces more ATP than it uses, ATP accumulates in the cytoplasm. The high concentration of ATP causes

glucose to be diverted away from glycolysis and into a pathway that builds glycogen. Liver and muscle cells especially favor the conversion of glucose to glycogen, and these cells contain the body’s largest stores of it. Between meals, the liver maintains the blood glucose level by breaking down the stored glycogen to release its glucose monomers.

What happens if you eat too many carbo- hydrates? When the blood level of glucose gets too high, acetyl–CoA is diverted away from the Krebs cycle and into a pathway that makes fatty acids. This is why excess dietary carbohydrate ends up as fat.

Fats A triglyceride molecule has a glycerol head and three fatty acid tails. Cells dismantle triglycerides in fats by first breaking the bonds that connect fatty acid tails to the glycerol head. Nearly all cells in the body can break down the released fatty acids for energy. First, their long backbones are split into two-carbon fragments. These fragments are converted to acetyl–CoA, which can enter the Krebs cycle. The glycerol released by triglyceride breakdown is converted by liver cells to an intermediate of glycolysis.

On a per carbon basis, fats are a richer source of energy than carbohydrates. This is because typical carbohydrate backbones have many oxygen atoms bonded to them. By con- trast, most fatty acid tails have no oxygen atoms bonded to them, so more reactions with oxygen are required to fully break their backbones apart. Coenzymes accept electrons in reactions that break apart carbon backbones. The more

Fats Complex Carbohydrates Proteins

PGAL acetyl–CoAacetyl–CoA

pyruvateNADH

NADH, FADH2

glycerol amino acidsglucose, other sugarsfatty acids

intermediate of Krebs cycle

Electron Transfer Phosphorylation

Krebs Cycle

ATP ATP

Food

Electron Transfer Phosphory lat ion

Glycolys is

Krebs Cycle

Figure 5.15 A variety of organic compounds from food can enter the reactions of aerobic respiration. Above, © shabaneiro/Shutterstock.com.

CAPTuRInG AnD RELEASInG EnERGy ChAptER 5 95

Take-Home Message 5.7 Can the body break down molecules other than sugars for energy?

• Breaking the carbon backbone of any organic molecule releases electrons. Those elec- trons carry energy that can be harnessed to drive ATP formation in aerobic respiration.

• First the digestive system and then individual cells convert molecules in food (complex carbohydrates, triglycerides, and proteins) into substrates of glycolysis or aerobic respiration’s second-stage reactions.

coenzymes that accept electrons, the more electrons can be delivered to the ATP- forming machinery of electron transfer phosphorylation.

Proteins Enzymes in the digestive system split dietary proteins into their amino acid subunits, which are absorbed into the bloodstream and used to build proteins or other molecules. When you eat more protein than your body needs for this purpose, the amino acids are broken down. The amino group is removed, and it becomes ammonia, a waste product eliminated in urine. The carbon backbone is split, and acetyl–CoA, pyruvate, or an intermediate of the Krebs cycle forms, depending on the amino acid. These molecules enter aerobic respiration’s second stage.

Biofuels A lot of energy is locked up in the chemical bonds of molecules made by plants. That energy can fuel consumers, as when an animal cell powers ATP synthesis by aerobic respiration. It can also fuel our cars, which run on energy released by burning biofuels or fossil fuels. Both processes are fundamentally the same: They release energy by breaking the bonds of organic molecules. Both use oxygen to break those bonds, and both produce carbon dioxide. unlike fossil fuels, biofuels are a renewable source of energy: we can always make more of them simply by growing more plants. Also unlike fossil fuels, biofuels do not contribute to global climate change, because growing plant matter for fuel recycles carbon that is already in the atmosphere.

Corn, soy, sugarcane, and other food crops are rich in oils, starches, and sugars that can be easily converted to biofuels. The starch in corn kernels, for example, can be enzymatically broken down to glucose, which is fermented to ethanol by bacteria or yeast. However, growing food crops for biofuel production typically requires a lot of energy (in the form of fossil fuels) and it damages the environment. Making biofuels from other plant matter such as weeds or agricultural waste requires additional steps, because these materials contain a higher proportion of cellulose. Breaking down this tough carbohydrate to its glucose monomers adds cost to the biofuel product.

In 2006, David Tilman and his colleagues published the results of a 10-year study comparing the net energy output of various biofuels. The researchers made biofuel from a mixture of native perennial grasses grown without irrigation, fertilizer, pesticides, or herbicides, in sandy soil that was so depleted by intensive agriculture that it had been abandoned. The energy content of this biofuel and the energy it took to produce it were measured and compared with that of biofuels made from food crops (Figure 5.16).

Figure 5.16 Energy inputs and outputs of various biofuels. Input: calculated energy used to grow the crop and produce the biofuel. Output: actual energy content of the biofuel. Corn and soy were grown on fertile farmland; grass, in depleted soil. One hectare is about 2.5 acres.

Digging Into Data

1. About how much energy did ethanol produced from one hectare of corn yield? How much energy did it take to grow and produce that ethanol?

2. which of the three crops required the least amount of land to produce a given amount of biofuel energy?

3. The production of which biofuel was most efficient (which had the highest ratio of energy output to energy input)?

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corn grain ethanol

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8.09 ratio of energy output to input:

output input

Summary Section 5.4 Carbon fixation occurs as part of the light-independent reactions of photosynthesis. in the stroma of chloroplasts, the Calvin–Benson cycle builds carbon backbones of sugars using carbon atoms from CO2. this cyclic pathway is driven by phosphate-

group transfers from atp and electrons delivered by nadpH (both of these molecules form during light-dependent reactions).

On hot, dry days, a plant conserves water by closing stomata, so carbon dioxide for the light-independent reactions cannot enter it, and oxygen produced by the light-dependent reactions cannot leave. Oxygen buildup in plant tissues reduces the efficiency of sugar production in C3 plants. additional carbon fixation reactions in C4 plants and CAM plants make sugar production more efficient on hot, dry days.

Section 5.5 When photosynthesis evolved, oxygen released by organisms that used it permanently changed the atmosphere, with profound effects on life’s evolution. Organisms that could not tolerate the increased atmospheric oxygen persisted only in anaerobic habitats. Oxygen-detoxifying pathways allowed other organisms to thrive under aerobic conditions.

Most modern organisms convert the chemical energy of carbohydrates to the chemical energy of atp by

oxygen-requiring aerobic respiration. in eukaryotes, this pathway starts with glycolysis in cytoplasm, and ends in mitochondria. Coenzymes pick up electrons in aerobic respiration’s first two stages, glycolysis and the Krebs cycle. the energy of those electrons drives atp synthesis in the third stage, electron transfer phosphorylation. at the end of the electron transfer chains, oxygen accepts electrons and hydrogen ions, so water forms. aerobic respiration yields about thirty-six atp per glucose.

Section 5.6 anaerobic fermentation pathways include alcoholic fermentation and lactate fermentation. Both begin with glycolysis, and they run in the cytoplasm. the electron acceptor at the end of these reactions is an organic molecule. the final steps

produce no atp. thus, the breakdown of one glucose molecule yields only the two atp from glycolysis.

Section 5.7 Organic molecules other than sugars can be broken down to make atp. in humans and other mammals, first the digestive system and then individual cells convert fats, proteins, and complex carbohydrates in food to molecules that are substrates of glycolysis or the second-stage reactions of aerobic respiration.

Section 5.1 By the pathway of photosynthesis, the energy of light is used to build sugars from water and carbon dioxide. photosynthesis removes CO

2 from the atmosphere, and the metabolic activity of most organisms puts it back. this global cycle was balanced

for millions of years. Human activities, especially burning fossil fuels, are currently disrupting the cycle by adding massive amounts of extra CO2 to the atmosphere. the resulting imbalance is fueling global climate change.

Section 5.2 light energy travels in waves. Visible light drives photosynthesis, which begins when light energy is absorbed by photosynthetic pigments. a pigment absorbs light of particular wavelengths only; wavelengths not captured are reflected as

its characteristic color. the main photosynthetic pigment, chlorophyll a, absorbs violet and red light, so it appears green. accessory pigments absorb additional wavelengths.

in chloroplasts, the light-dependent reactions of photosynthesis occur at a much-folded thylakoid membrane. the light-independent reactions occur in the chloroplast’s cytoplasm-like stroma. an overview is shown below:

Section 5.3 Clusters of photosynthetic pigments in the thy lakoid membrane absorb the energy in light and pass it to photosystems. receiving energy causes

photosystems to release electrons. the electrons flow through electron transfer chains in the thylakoid membrane, and end up in nadpH. Molecules of the electron transfer chain use energy released by the electrons to set up a hydrogen ion gradient across the thylakoid membrane. the ions move back across the membrane through atp synthases embedded in it. the flow causes these proteins to produce atp, a process called electron transfer phosphorylation.

photosynthesis releases oxygen because a photosystem replaces lost electrons by pulling them from water molecules, which break apart into hydrogen ions and oxygen as a result.

light- dependent reactions

light-

reactions

sugarsoxygen

carbon dioxide

NADPH, ATP

NADP+, ADP

water

lig

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ions

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CO2

sugar

1. While looking into an aquarium, you see bubbles coming from an aquatic plant (right). What are the bubbles?

2. How is the function of the thylakoid mem- brane similar to that of the inner mitochondrial membrane?

3. Which of the following is not produced by an animal muscle cell operating under anaerobic conditions? a. heat c. atp e. pyruvate b. lactate d. nad+ f. all are produced

4. the bar-tailed godwit is a type of shorebird that makes an annual migration from alaska to new Zealand and back. the birds make each 11,500-kilometer (7,145-mile) trip by flying over the pacific Ocean in about nine days. One bird was observed to make the entire journey uninterrupted, a feat that is com- parable to a human running a nonstop seven-day marathon at 70 kilometers (43.5 miles) per hour. Would you expect the flight (breast) muscles of bar-tailed godwits to be light or dark colored? explain your answer.

Answers in Appendix i

1. Most of the carbon that land plants use for photosynthesis comes from . a. glucose c. water b. the atmosphere d. soil

2. plants use as an energy source to drive photosynthesis. a. sunlight c. O2 b. sugars d. CO2

3. Which of the following statements is incorrect? a. pigments absorb light of certain wavelengths only. b. Many accessory pigments are multipurpose molecules. c. Chlorophyll a is green because it absorbs green light.

4. in the light-dependent reactions, . a. carbon dioxide is fixed c. CO2 accepts electrons b. atp forms d. sugars form

5. When a photosystem absorbs light, . a. sugar phosphates are produced b. electrons are transferred to atp c. it ejects electrons

6. the atoms in the oxygen molecules released during photosynthesis come from . a. glucose b. CO2 c. water d. O2

7. the Calvin–Benson cycle starts when . a. light is available b. carbon is fixed c. electrons leave a photosystem

8. Closed stomata . a. limit gas exchange c. restrict photosynthesis b. permit water loss d. absorb light

9. true or false? plants make all of their atp by photosynthesis.

10. in the third stage of aerobic respiration, is the final acceptor of electrons. a. water b. H+ c. O2 d. nadH

11. in eukaryotes, the final reactions of aerobic respiration are completed in . a. the nucleus c. the plasma membrane b. mitochondria d. cytoplasm

12. in eukaryotes, the final reactions of fermentation are completed in . a. the nucleus c. the plasma membrane b. mitochondria d. cytoplasm

13. your body cells can break down as a source of energy to fuel atp production. a. fatty acids c. amino acids b. glycerol d. all of the above

14. Which of the following metabolic pathways require(s) molecular oxygen (O2)? a. aerobic respiration c. alcoholic fermentation b. lactate fermentation d. photosynthesis

15. Match the term with the best description. pyruvate a. no oxygen required anaerobic b. converts light to chemical energy mitochondrion c. product of glycolysis pigment d. aerobic respiration in eukaryotes carbon dioxide e. carbon-fixing enzyme rubisco f. like an antenna photosynthesis g. big in the atmosphere

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Critical thinking

self-Quiz

6.1 Cloning 100

6.2 Fame, Glory, and DNA Structure 102

6.3 DNA in Chromosomes 106

6.4 DNA Replication and Repair 108

D N

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100 Unit 2 GeNetiCS

Application

Figure 6.1 Examples of adult animal cloning. (A) left, Splash News/Newscom; right, Ben Glass, courtesy of © BioArts International; (B) Courtesy of Cyagra, Inc.

A. Left, James Symington and his dog trakr assisted in the search for victims at Ground Zero, September 2001. Symington wrote an essay about trakr’s superior abilities in search and rescue operations such as this one, and won an opportunity to have the dog cloned. Right, Symington with trakr’s clones in 2009.

6.1 Cloning REMEMBER: A cell’s DNA contains all of the information necessary to build a new cell and, in the case of multicelled organisms, an entire individual (Section 2.10).

On September 11, 2001, Constable James Symington drove his search dog Trakr from Nova Scotia to Manhattan. Within hours of arriving, the dog led rescuers to the area where the final survivor of the World Trade Center attacks was buried. She had been clinging to life, pinned under rubble from the building where she had worked. Symington and Trakr helped with the search and rescue efforts for three days nonstop, until Trakr collapsed from smoke and chemical inhalation, burns, and exhaustion.

Trakr survived the ordeal, but later lost the use of his limbs from a degenerative neurological disease probably linked to toxic smoke exposure at Ground Zero. The hero dog died in April 2009, but his DNA lives on in his genetic copies—his clones. Symington’s essay about Trakr’s superior nature and abilities as a search and rescue dog won the Golden Clone Giveaway, a contest to find the world’s most clone- worthy dog. Trakr’s DNA was shipped to Korea, where it was inserted into donor dog eggs, which were then implanted into surrogate mother dogs. Five puppies, all clones of Trakr, were delivered to Symington in July 2009 (Figure 6.1A). Today, Trakr’s clones are search and rescue dogs for Team Trakr Foundation, an interna- tional humanitarian organization that Symington established in 2010.

Trakr’s clones were produced by somatic cell nuclear transfer (SCNT), a labo- ratory procedure in which an unfertilized egg’s nucleus is replaced with the nucleus of a donor’s somatic cell (Figure 6.2). A somatic cell is a body cell, as opposed to a reproductive cell (soma is a Greek word that means body). If all goes well, the egg’s cytoplasm reprograms the transplanted DNA to direct the development of an embryo, which is then implanted into a surrogate mother. The animal born to the surrogate is a clone of the donor.

SCNT is possible because all cells descended from a fertilized egg inherit the same DNA. That DNA is like a master blueprint that directs the development of the individual’s body. Thus, the DNA in each body cell of a multicelled individual

B. Champion dairy cow Liz (right) and her clone, Liz ii (left). Liz ii, who was produced by SCNt, had already begun to win championships by the time she was one year old.

The DNA in each body cell of a multicelled individual contains all the information necessary to build the individual all over again.

DNA StRUCtURe AND FUNCtioN ChAptER 6 101

contains all the information necessary to build the individual all over again. In fact, clones occur all the time in nature. Body cells of many plants and some animal spe- cies easily give rise to new individuals that are clones of the parent. Identical twins are the product of embryo splitting, another natural process. The first few divisions of a fertilized egg form a ball of cells that sometimes splits spontaneously. If both halves of the ball continue to develop independently, identical twins result. Humans have long exploited this phenomenon with a technique called artificial embryo splitting. A tiny ball of cells is grown from a fertilized egg in a laboratory. The ball is teased apart into two halves, each of which goes on to develop as a separate embryo. The embryos are implanted in surrogate mothers, who give birth to identical twins.

Twins produced by embryo splitting are identical to one another, but they are not identical to either parent. This is because, in humans and other animals, twins get their DNA from two parents that typically differ in their DNA sequence (Chap- ter 8 returns to this topic). Thus, animal breeders who want a clone of a specific individual use SCNT. Clones produced by SCNT have the same championship fea- tures as their adult donor animals (Figure 6.1B), and there are other benefits. SCNT can yield many more offspring in a given time frame than traditional breeding, and offspring can be produced from a donor animal that is castrated or even dead.

“Cloning” means making an identical copy of something, and it can refer to deliberate interventions in reproduction intended to produce an exact genetic copy of an organism. Reproductive cloning refers to any technology, especially SCNT, that yields animal clones. SCNT has been used since 1997, when a lamb called Dolly was cloned from a mammary cell of an adult sheep (the clone was named after voluptuous performer Dolly Parton). At first, Dolly looked and acted like a normal sheep. However, she died early, most likely because she was a clone. SCNT is techni- cally challenging and the outcome is still unpredictable. Depending on the species, few implanted embryos may survive until birth. Until recently, most of the clones that did survive had serious health problems such as enlarged organs and obesity. Cloned mice developed lung and liver problems, and almost all died prematurely. Cloned pigs tended to limp and have heart problems; some developed without a tail or, even worse, an anus.

Why the problems? Even though a somatic cell contains all the DNA required to produce a new individual, it will not automatically start dividing and form an embryo. During early development, an embryo’s cells start using different subsets of their DNA. As they do, the cells become different in form and function, a process called differentiation. Differentiation is usually a one-way path in animal cells, which means that once a cell has become specialized, all of its descendant cells will be specialized the same way. By the time a liver cell, muscle cell, or other dif- ferentiated cell forms, most of its DNA has been turned off, and is no longer used (Chapter 10 returns to this topic). To clone an adult, scientists must transform one of its differentiated cells into an undifferentiated cell by turning the unused DNA back on, reprogramming it to function like the DNA of an egg. Even though we are getting better at doing that, we still have quite a bit to learn. SCNT technology has improved so much in recent years that health problems are much less common in animals cloned today.

Cloning animals brings us closer to the possibility of cloning humans, both technically and ethically. The idea raises uncomfortable ethical questions. For example, if cloning a lost animal for a grieving owner is acceptable, why would it not be acceptable to clone a lost child for a grieving parent? Different people have very different answers to such questions, so controversy over cloning continues to rage even as the technique improves.

clone Genetically identical copy of an organism.

differentiation Process by which cells become specialized during development.

reproductive cloning Any of several laboratory pro- cedures that produce genetically identical animals.

somatic cell nuclear transfer (SCnt) Reproductive cloning method in which the DNA of an adult donor’s body cell is transferred into an unfertilized egg.

A. A cow’s egg is held in place by suction through a hollow glass tube called a micropipette. DNA is identified by a purple stain.

B. Another micropipette punctures the egg and sucks out the DNA. All that remains inside the egg’s plasma membrane is cytoplasm.

C. A new micropipette prepares to enter the egg at the puncture site. the pipette contains a cell grown from the skin of a donor animal.

D. the micropipette enters the egg and delivers the skin cell to a region between the cytoplasm and the plasma membrane.

E. After the pipette is withdrawn, the donor’s skin cell is visible next to the cytoplasm of the egg. the transfer is complete.

F. An electric current causes the foreign cell to fuse with and empty its nucleus into the cyto- plasm of the egg. the egg begins to divide, and an embryo forms.

Figure 6.2 Somatic cell nuclear transfer (SCnt) with cells from cattle. this series of micrographs was taken by scientists at Cyagra, a company that specializes in cloning livestock. Courtesy of Cyagra, Inc., www.cyagra.com.

102 Unit 2 GeNetiCS

6.2 Fame, Glory, and DNA Structure REMEMBER: Radioisotope tracers (Section 2.2) were used in research that led to the discovery that DNA is the hereditary material of all organisms. Protein structure varies greatly, but patterns such as helices are common (2.9). DNA is a polymer of nucleotides that have been linked into a chain (2.10).

Discovery of DNA’s Function DNA, the substance (Figure 6.3), was first described in 1869 by Johannes Miescher, a chemist who extracted it from cell nuclei. Miescher determined that DNA is not a protein, and that it is rich in nitrogen and phosphorus, but he never learned its function. Sixty years later, Frederick Griffith unexpectedly found a clue. Griffith was studying pneumonia-causing bacteria in the hope of creating a vaccine. He discovered that these deadly bacteria contained a substance that could transform harmless bacteria into lethal ones. The transforma- tion was permanent and heritable: Even after hundreds of generations, descendants of transformed cells retained the ability to kill.

What was the substance that had caused this transformation? In 1940, Oswald Avery and Maclyn McCarty set out to identify the substance, which they called the “transforming principle.” The team extracted lipids, proteins, and nucleic acids from pneumonia-causing bacteria, then used a process of elimination to see which compo- nent transformed harmless bacteria into killers. Treating the extract with lipid- and protein-destroying enzymes did not destroy the transforming principle. Thus, the substance could not be lipid or protein. Avery and McCarty realized that the trans- forming principle must be nucleic acid—DNA or RNA. DNA-degrading enzymes destroyed the extract’s ability to transform cells, but RNA-degrading enzymes did not. Thus, DNA had to be the transforming principle.

The result surprised Avery and McCarty, who, along with most other scientists, had assumed that proteins were the material of heredity. After all, traits are diverse, and proteins are the most diverse of all biological molecules. The two scientists were so skeptical that they published their results only after they had convinced them- selves, by years of painstaking experimentation, that DNA was indeed hereditary material. They were also careful to point out that they had not proven DNA was the only hereditary material.

Avery and McCarty’s tantalizing results prompted a stampede of other scientists into the field of DNA research. The resulting explosion of discovery confirmed the molecule’s role as carrier of hereditary information. Key in this advance was the realization that any molecule—DNA or otherwise—had to have certain properties in order to function as hereditary material. First, a full complement of hereditary information must be transmitted along with the molecule; second, cells of a given species should contain the same amount of it; third, because the molecule functions as a genetic bridge between generations, it has to be exempt from major change; and fourth, it must be capable of encoding the almost unimaginably huge amount of information required to build a new individual.

In the late 1940s, Alfred Hershey and Martha Chase proved that DNA, and not protein, satisfies the first property of a hereditary molecule: It transmits a full com- plement of hereditary information. Hershey and Chase specialized in working with bacteriophages, a type of virus that infects bacteria. Like all viruses, these infectious particles carry information about how to make new viruses in their hereditary mate- rial. After a virus injects a cell with this material, the cell starts making new virus particles. Hershey and Chase carried out an elegant series of experiments proving that the material a bacteriophage injects into bacteria is DNA, not protein.

Figure 6.3 human DnA, the substance. DNA’s role as the carrier of hereditary information was uncovered over many years, as scientists built upon one another’s discoveries. Patrick Landmann/Science Source.

DNA STRUCTURE AND FUNCTioN Chapter 6 103

Digging Into Data the hershey–Chase experiments By 1950, researchers had discovered bacteriophages, a type of virus that infects bacteria. Like all viruses, these infectious particles carry hereditary infor- mation about how to make new viruses. After a virus infects a cell, the cell starts making new virus particles. Bacteriophages inject genetic material into bacteria, but was that material DNA, protein, or both? Alfred Hershey and Martha Chase carried out experiments to determine the composition of that mate- rial. These experiments were based on the knowledge that proteins contain more sulfur (S) than phosphorus (P), and DNA contains more phosphorus than sulfur. Bacteriophage DNA and protein were labeled with radioactive tracers and allowed to infect bacteria. The virus–bacteria mixtures were then whirled in a blender to dislodge any viral components attached to the exterior of the bacteria (Figure 6.4). Afterward, radioactivity from the tracers was measured. The graph shown in Figure 6.4C, which summarizes results from these experiments, is reproduced from an original publication by Hershey and Chase.

a. in one experiment, bacteriophage were labeled with a radioisotope of sulfur (35S), a process that makes their protein components radioactive. The labeled viruses were mixed with bacteria long enough for infection to occur, and then the mixture was whirled in a kitchen blender. Blending dislodged viral parts that remained on the outside of the bacteria. Afterward, most of the radioactive sulfur was detected outside the bacterial cells. The viruses had not injected protein into the bacteria.

Virus particle coat proteins labeled with 35S

DNA being injected into bacterium

Virus DNA labeled with 32P

Labeled DNA being injected into bacterium

outside cells

inside cells

35S remains

32P remains

B. in another experiment, bacteriophage were labeled with a radioisotope of phosphorus (32P), which makes their DNA radioactive. The labeled viruses were allowed to infect bacteria. After the external viral parts were dislodged from the bacteria, the radioactive phosphorus was detected mainly inside the bacterial cells. The viruses had injected DNA into the cells—evidence that DNA is the genetic material of this virus.

Virus particle coat proteins labeled with 35S

DNA being injected into bacterium

Virus DNA labeled with 32P

Labeled DNA being injected into bacterium

outside cells

inside cells

35S remains

32P remains

Figure 6.4 hershey–Chase experiments.

1. Before blending, what percent- age of each isotope, 35S and 32P, was outside of the bacteria (extracellular)?

2. After 4 minutes in the blender, what percentage of each isotope was extracellular?

3. How did the researchers know that the radioisotopes in the fluid came from outside of the bacterial cells and not from bacteria that had been broken apart by whirling in the blender?

4. The extracellular concentration of which isotope increased the most with blending? Why do these results imply that bacteriophage viruses inject DNA into bacteria?

Three bacteriophage particles injecting DNA into an E. coli bacterium

Eye of Science/Science Source.

C. Detail from Alfred Hershey and Martha Chase’s publication describing their experiments with bacte- riophages. in this graph, “infected bacteria” refers to the percentage of bacteria that survived the blender. Journal of General Physiology, 36(1), Sept. 20, 1952.

104 Unit 2 GeNetiCS

Variations in the sequence of DNA are the foundation of life’s diversity.

Discovery of DNA’s Structure DNA is a polymer of four types of nucleotides— adenine (A), guanine (G), thymine (T), and cytosine (C). Each has a five-carbon sugar, three phosphate groups, and a nitrogen- containing base after which it is named (Figure 6.5). Just how those four nucleotides are arranged in a DNA mole- cule was a puzzle that took over 50 years to solve. As molecules go, DNA is gigantic, and chromosomal DNA has a complex structural organization; both factors made the molecule difficult to work with given the laboratory methods at the time.

Clues about DNA’s structure started coming together around 1950, when Erwin Chargaff (one of many researchers investigating its function) made two important discoveries about the molecule. First, the amounts of thymine and adenine are iden- tical, as are the amounts of cytosine and guanine (A = T and G = C). We call this discovery Chargaff ’s first rule. Chargaff ’s second discovery, or rule, is that the DNA of different species differs in the proportions of adenine and guanine.

Meanwhile, biologist James Watson and biophysicist Francis Crick had been sharing ideas about the structure of DNA. The helical (coiled) pattern of second- ary structure that occurs in many proteins had just been discovered, and Watson and Crick suspected that the DNA molecule was also a helix. The two spent many hours arguing about the size, shape, and bonding requirements of the four DNA nucleotides. They pestered chemists to help them identify bonds they might have overlooked, fiddled with cardboard cutouts, and made models from scraps of metal connected by suitably angled “bonds” of wire.

Biochemist Rosalind Franklin (right) had also been work- ing on the structure of DNA. Like Crick, Franklin was expert in x-ray crystallography, a technique in which x-rays are directed through a purified and crystallized substance. Atoms in the substance’s molecules scatter the x-rays in a pattern that can be captured as an image. Researchers can use the pattern to calcu- late the size, shape, and spacing between any repeating elements of the molecules—all of which are details of molecular structure.

Franklin had been told she would be the only one in her department working on the structure of DNA, so she did not know that Maurice Wilkins was already doing the same thing just down the hall. No one had told Wilkins about Franklin’s assignment; he assumed she was a technician hired to do his x-ray crystallography work. And so a clash began. Wilkins thought Franklin displayed an appalling lack of deference that technicians of the era usually accorded researchers. To Franklin, Wilkins seemed prickly and oddly overinterested in her work.

adenine (A)

deoxyadenosine triphosphate

NH2

C N

CHC N

CH2

PPP

guanine (G)

deoxyguanosine triphosphate

C NH

CC N

N NH2

CH2

PPP

thymine (T)

deoxythymidine triphosphate

C NH

C OHC N

CH3

CH2

PPP

cytosine (C) deoxycytidine triphosphate

NH2

C N

C OHC N

CH2

PPP

three phosphate groups

sugar

base

Figure 6.5 the four nucleotides that make up DnA. each kind has three phosphate groups, a deoxyribose sugar (orange), and a nitrogen-containing base (blue) after which it is named.

N LM

DNA StRUCtURe AND FUNCtioN ChAptER 6 105

Figure 6.6 Structure of DnA, as illustrated by a com- posite of three different models. the two sugar–phosphate backbones coil in a helix around internally positioned bases.

Figure it Out: What do the yellow balls represent?

Answer: Phosphate groups Wilkins and Franklin had been given identical samples of DNA. Franklin’s

meticulous work with hers yielded the first clear x-ray diffraction image of DNA as it occurs in cells. She gave a presentation on this work in 1952. DNA, she said, had two chains twisted into a double helix, with a backbone containing phosphate groups on the outside, and bases arranged in an unknown way on the inside. She had calculated DNA’s diameter, the distance between its chains and between its bases, the angle of the helix, and the number of bases in each coil. Crick, with his crystallography background, would have recognized the significance of the work—if he had been there. Watson was in the audience but he was not a crystallographer and did not understand the implications of Franklin’s data.

Franklin started to write a research paper on her findings. Meanwhile, and perhaps without her knowledge, Watson reviewed Franklin’s x-ray diffraction image with Wilkins, and Watson and Crick read a report detailing Franklin’s unpublished data. Crick, who had more experience with molecular modeling than Franklin, immediately understood what the image and the data meant. Franklin’s

data provided Watson and Crick with the last piece of the DNA puzzle. In 1953, they put together all of the clues that had been accumulating for the last fifty years and built the first accurate model of the DNA molecule (left). On April 25, 1953, Franklin’s paper appeared third in a series of articles about the structure of DNA in the journal Nature. It supported with solid experimental evidence Watson and Crick’s theoretical model, which appeared in the first article of the series.

Watson and Crick proposed that a DNA molecule consists of two chains (or strands) of nucleotides, running in opposite directions and coiled into a double helix (Figure 6.6). Covalent bonds between the sugar of one nucleotide and a phosphate of the next form the sugar–phosphate backbone of each chain. Hydro- gen bonds between the internally positioned bases hold the two strands together. Only two kinds of base pairings form: A to T, and G to C, which explains the first of Chargaff ’s rules. Most scientists had assumed (incorrectly) that the bases had to be on the outside of the helix, because they would be more accessible to DNA-copying enzymes that way. You will see in Section 6.4 how these enzymes access the nucleo- tide bases on the inside of the double helix.

Dozens of scientists contributed to the discovery of DNA’s structure, but only three received recognition from the general public for their work. Rosalind Franklin died in 1958. Because the Nobel Prize is not given posthumously, she did not share in the 1962 honor that went to Watson, Crick, and Wilkins for the discovery of the structure of DNA.

DNA Sequence A small piece of DNA from a tulip, a human, or any other organ- ism might be:

Tone base pair

Notice how the two strands of DNA fit together. They are complementary—the base of each nucleotide on one strand pairs with a suitable partner base on the other. This base-pairing pattern (A to T, G to C) is the same in all molecules of DNA. How can just two kinds of base pairings give rise to the incredible diversity of traits we see among living things? Even though DNA is composed of only four

C. B

ar rin

gt on

B ro

w n

96 8

J. D

. W at

so n

Hydrogen bonds link internally positioned nucleotide bases.

A phosphate group links the sugar of one nucleotide to the sugar of the next. These bonds form each strand’s sugar–phosphate backbone.

106 Unit 2 GeNetiCS

6.3 DNA in Chromosomes REMEMBER: the DNA of a eukaryotic cell is contained in a nucleus (Section 3.5).

Stretched out end to end, the DNA molecules in a single human cell would be about 2 meters (6.5 feet) long. How can that much DNA cram into a nucleus that is less than 10 micrometers in diameter? Inside a cell, proteins that associate with each DNA molecule twist and pack it into a structure called a chromosome (Figure 6.7). In a eukaryotic cell, for example, a DNA molecule

wraps twice at regular inter- vals around “spools” of proteins called histones

. These DNA–histone spools look a bit like beads on a string in micrographs. Interactions among histones and other proteins twist the spooled DNA into a tight fiber

. This fiber coils, and then it coils again into a hollow cylinder like an old-style telephone cord

. During most of the cell’s life, each chromosome consists of one DNA molecule.

When the cell prepares to divide, it duplicates its chromosomes (more about this process in the next section). After replication, each chromosome consists of two DNA molecules, or sister chromatids, attached to one another at a constricted region called the centromere:

one chromatid

centromere

its sister chromatid

a chromosome (unduplicated)

a chromosome (duplicated)

The duplicated chromosomes condense into their familiar “X” shapes 5

just prior to cell division.

The DNA of a eukaryotic cell is divided up among some number of chromo- somes that differ in length and shape

. That number is called the chromosome number, and it is a characteristic of the species. For example, the chromosome number of humans is 46, so our cells have 46 chromosomes.

Take-Home Message 6.2 What is DnA?

• DNA is the molecule of inheritance in all organisms. • A DNA molecule consists of two nucleotide chains (strands) coiled into a double helix.

Hydrogen bonding between internally positioned nucleotide bases (A pairs with t, and C with G) hold the two strands together.

• the sequence of bases along a DNA strand—the DNA sequence—varies among spe- cies and among individuals. this variation is the basis of life’s diversity.

nucleotides, the order in which one nucleotide follows the next along a strand—the DNA sequence—varies tremendously among species (which explains Chargaff ’s second rule). DNA molecules can be hundreds of millions of nucleotides long, so their sequence can encode a massive amount of information (we return to the nature of that information in the next chapter). DNA sequence variation is the basis of traits that define species and distinguish individuals. Thus DNA, the molecule of inheritance in every cell, is the basis of life’s unity. Variations in its sequence are the foundation of life’s diversity.

Figure 6.7 Eukaryotic chromosome structure. the micrograph shows a duplicated chromosome just before cell division. Andrew Syred/Science Source.

two strands of DNA twist into a double helix.

At regular intervals, the DNA (blue) wraps around a core of histone proteins (purple).

the DNA and proteins associated with it twist tightly into a fiber.

the fiber coils and then coils again to form a hol- low cylinder.

At its most condensed, a duplicated chromosome has an X shape.

the DNA in the nucleus of a typical eukaryotic cell is divided into a number of chromosomes.

Figure it Out: What is the yellow structure in the upper right corner of the drawing? Answer: A cell nucleus

2 µm

DNA StRUCtURe AND FUNCtioN ChAptER 6 107

Actually, human body cells have two sets of 23 chromosomes—two of each type. Having two sets of chromosomes means these cells are diploid, or 2n. An image of an individual’s diploid set of chromosomes is called a karyotype (Fig- ure 6.8). To create a karyotype, cells taken from the individual are treated to make the chromosomes condense, and then stained so the chromosomes can be distin- guished under a microscope. A micrograph of a single cell is digitally rearranged so the images of the chromosomes are lined up by centromere location, and arranged according to size, shape, and length.

In a human body cell, all but one pair of chromosomes are autosomes, which are the same in both females and males. The two autosomes of a pair have the same length, shape, and centromere location. They also hold information about the same traits. Think of them as two sets of books on how to build a house. Your father gave you one set. Your mother had her own ideas about wiring, plumbing, and so on. She gave you an alternate set that says slightly different things about many of those tasks.

Members of a pair of sex chromosomes differ between females and males, and the differences determine an individual’s sex. The sex chromosomes of humans are called X and Y. The body cells of typical human females have two X chromosomes (XX, Figure 6.8A); those of typical human males have one X and one Y chromo- some (XY). This pattern—XX females and XY males—is the rule among fruit flies, mammals, and many other animals, but there are other patterns (Figure 6.8B). Female butterflies, moths, birds, and certain fishes have two nonidentical sex chro- mosomes; the two sex chromosomes of males are identical. Environmental factors (not chromosomes) determine sex in some species of invertebrates, turtles, and frogs. As an example, the temperature of the sand in which sea turtle eggs are buried determines the sex of the hatchlings.

Take-Home Message 6.3 What is a chromosome?

• A chromosome is a molecule of DNA together with associated proteins that organize it and allow it to pack tightly.

• A eukaryotic cell’s DNA is divided among a characteristic number of chromosomes, which differ in length and shape.

• Members of a pair of sex chromosomes differ between males and females. Chromo- somes that are the same in both sexes are called autosomes.

autosome A chromosome that is the same in males and females.

centromere of a duplicated eukaryotic chromosome, constricted region where sister chromatids attach to each other.

chromosome Structure that consists of DNA together with associated proteins; carries part or all of a cell’s genetic information.

chromosome number the total number of chromo- somes in a cell of a given species.

diploid Having two of each type of chromosome characteristic of the species (2n). DnA sequence order of nucleotides in a strand of DNA.

histone type of protein that associates with eukary- otic DNA and structurally organizes chromosomes.

karyotype image of an individual’s complement of chromosomes arranged by size, length, shape, and centromere location.

sex chromosome Member of a pair of chromosomes that differs between males and females.

sister chromatids the two attached DNA molecules of a duplicated eukaryotic chromosome.

Figure 6.8 Karyotypes. Chromosomes are numbered (as shown). (A) © University of Washington Department of Pathology; (B) With kind permission from Springer Science+Business Media: Chromosome Research, Volume 17, Number 1, 99 113, DOI: 10.1007/s10577-009-9021-6; Avian comparative genomics: reciprocal chromo- some painting between domestic chicken (Gallus gallus) and the stone curlew (Burhinus oedicnemus, Charadriiformes)—An atypical species with low diploid number; Wenhui Nie, Patricia C. M. O’Brien, Bee L. Ng, Beiyuan Fu, Vitaly Volobouev, Nigel P. Carter, Malcolm A. Ferguson-Smith, and Fengtang Yang; Figure 2a.

1 2 3 4 5

6 7 8 9 10 11 12

13 14 15 16 17 18

20 21 22 X Y19

A. Karyotype of a female human, with identical sex chromosomes (XX). B. Karyotype of a female chicken, with nonidentical sex chromosomes (ZW).

1 2 3 4 5 6 7

8 9 10 11 12 13 14

15 16 17 18 2019 Z W

6.4 DNA Replication and Repair REMEMBER: With a few exceptions, free radicals are dangerous to life (Section 2.2). An enzyme speeds a reaction; bonds between phosphate groups hold a lot of energy (4.4). the wavelength of light is measured in nanometers (5.2).

When a cell reproduces, it divides. The two descendant cells must inherit a complete copy of genetic information or they will not function properly. Thus, in prepara- tion for division, the cell copies its chromosomes so that it contains two sets: one for each of its future offspring. The copying process is an energy-intensive path- way called DNA replication. During DNA replication, the double helix of a DNA molecule is opened to expose the internally positioned bases, and an enzyme, DNA polymerase, links nucleotides into new strands of DNA according to the sequence of those bases. Each chromosome is copied in its entirety. Two identical molecules of DNA are the result. In eukaryotes, these molecules are sister chromatids that remain attached at the centromere until cell division occurs.

Before DNA replication, a chromosome has one molecule of DNA—one double helix (Figure 6.9). As replication begins, enzymes break the hydrogen bonds that hold the double helix together, so the two DNA strands unwind and separate

. Another enzyme starts making primers, which are short, single strands of nucleo- tides that serve as attachment points for DNA polymerase

. The nucleotide bases of a primer can form hydrogen bonds with the exposed bases of a single strand of DNA. Thus, a primer can base-pair with a complementary strand of DNA (right). The establishment of base pairing between two strands of DNA (or DNA and RNA) is called hybridization. Hybridization is spontaneous and is driven entirely by hydrogen bonding.

DNA polymerases attach to the hybridized primers and begin DNA synthesis. As a DNA polymerase moves along a strand, it uses the sequence of exposed nucleotide bases as a template, or guide, to assemble a new strand of DNA from free nucleotides 3

. Two of a nucleotide’s three phosphate groups are removed when it is added to a DNA strand. Breaking those bonds releases enough energy to drive the attachment.

A DNA polymerase follows base-pairing rules: It adds a T to the end of the new DNA strand when it reaches an A in the template strand; it adds a G when it reaches a C; and so on. Thus, the DNA sequence of each new strand is complementary to the template (parental) strand. The enzyme DNA ligase seals any gaps, so the new DNA strands are continuous

. Both strands of the parent molecule are copied at the same time. As each new DNA strand lengthens, it winds up with the template strand into a double helix. So, after replication, two double-stranded molecules of DNA have formed

. One strand of each molecule is conserved (parental), and the other is new, so replication is said to be semiconservative. Both double-stranded molecules produced by DNA replication are duplicates of the parent molecule.

How Mutations Arise Sometimes, a new DNA strand is not exactly comple- mentary to its parent strand. A nucleotide may get lost during DNA replication, or an extra one slips in. Occasionally, the wrong nucleotide is added. Most of these replication errors occur simply because DNA polymerases work very fast. Mistakes are inevitable, and some DNA polymerases make a lot of them. Luckily, most DNA polymerases also proofread their work. They can correct a mismatch by reversing

DNA polymerase

DNA ligase

primer

enzymes

Figure 6.9 DnA replication.

As replication begins, enzymes begin to unwind and separate the two strands of DNA.

Primers base-pair with the exposed single DNA strands.

Starting at primers, DNA polymerases (green boxes) assemble new strands of DNA from nucleotides, using the parent strands as templates.

DNA ligase seals any gaps that remain between bases of the “new” DNA.

each parental DNA strand (blue) serves as a template for assembly of a new strand of DNA (magenta). Both strands of the double helix serve as templates, so two double-stranded DNA molecules result. one strand of each is parental (old), and the other is new, so DNA replication is semiconservative.

DNA

primer

108 Unit 2 GeNetiCS

DNA StRUCtURe AND FUNCtioN ChAptER 6 109

Take-Home Message 6.4 What happens during DnA replication?

• When a cell copies its DNA, each strand of the double helix serves as a template for synthesis of a new, complementary strand of DNA. two double helices result.

• Proofreading and repair mechanisms usually maintain the integrity of a cell’s genetic information by correcting mispaired bases and fixing damaged DNA before replication.

• Mismatched or damaged nucleotides that are not repaired become mutations. • DNA damage by environmental agents such as UV light, chemicals, and free radicals

can result in mutations, because damaged DNA is not replicated very well.

the synthesis reaction to remove the mispaired nucleotide, then resuming synthesis in the forward direction. Replication errors also occur after the cell’s DNA gets bro- ken or otherwise damaged, because DNA polymerases do not copy damaged DNA very well. In most cases, repair enzymes and other proteins remove and replace damaged or mismatched bases in DNA before replication begins.

When proofreading and repair mechanisms fail to correct an error, it becomes a mutation—a permanent change in the DNA sequence of a cell’s chromosome(s). Repair enzymes cannot fix a mutation after the altered DNA strand has been rep- licated, because they do not recognize correctly paired bases (Figure 6.10). Thus, a mutation is passed to one of the cell’s offspring and all of its descendants.

Mutations alter DNA’s genetic instructions, so they may have a harmful outcome. Cancer begins with mutations. Rosalind Franklin died at the age of 37, of ovarian cancer probably caused by extensive exposure to x-rays during her work. At the time, the link between x-rays, mutations, and cancer was not under- stood. We now know that electromagnetic energy with a wavelength shorter than 320 nanometers, including x-rays, most ultraviolet (UV) light, and gamma rays, has enough energy to knock electrons out of atoms. Exposure to such ionizing radiation damages DNA, breaking it into pieces that get lost during replication (Figure 6.11). Ionizing radiation can also cause covalent bonds to form between bases on opposite strands of the double helix, an outcome that permanently blocks DNA replication. The nucleotide bases themselves can be irreparably damaged by ionizing radiation. Repair enzymes remove bases damaged in this way, but they leave an empty space in the double helix or even a strand break. Any of these events can result in mutations.

UV light in the range of 320 to 380 nanometers does not have enough energy to knock electrons out of atoms, but it can cause a covalent bond to form between adjacent thymine or cytosine bases. The result is a nucleotide dimer that kinks the DNA strand. DNA polymerase tends to copy the kinked part incorrectly during replication, and mutations are the outcome. Exposing unprotected skin to sunlight increases the risk of cancer because the UV wavelengths cause these nucleotide dimers to form. For every second a skin cell spends in the sun, between 50 and 100 nucleotide dimers form in its DNA.

Exposure to some chemicals also causes mutations. For instance, several of the fifty-five or more cancer-causing chemicals in tobacco smoke transfer methyl groups (—CH3) to the nucleotide bases in DNA. Nucleotides altered in this way do not base-pair correctly. The body converts other chemicals in the smoke to com- pounds that bind irreversibly to DNA. In both cases, the resulting replication errors can lead to mutation. Cigarette smoke also contains free radicals, which inflict the same damage on DNA as ionizing radiation.

DnA polymerase enzyme that carries out DNA replication.

DnA replication Process by which a cell duplicates its DNA before it divides.

mutation Permanent change in DNA sequence.

primer Short, single strand of DNA that base-pairs with a specific DNA sequence.

A. Repair enzymes can recognize a mismatched base (yellow), but they sometimes fail to correct it before DNA replication.

B. After replication, both strands base-pair properly. Repair enzymes can no longer recognize the error, which has now become a mutation that will be passed on to the cell’s descendants.

Figure 6.10 how replication errors become mutations.

Figure 6.11 Why exposure to ionizing radiation causes mutations. this micrograph shows major breaks (red arrows) in the chromosomes of human white blood cells that have been exposed to ionizing radiation. Pieces of broken chromo- somes often become lost during DNA replication. Olga Shovman, Andrew C. Riches, Douglas Adamson, and Peter E. Bryant. An improved assay for radiation-induced chromatid breaks using a colcemid block and calyculin-induced PCC combination. Mutagenesis (2008) 23(4): 267–270; first published online March 6, 2008. doi:10.1093/mutage/gen009, by permission of Oxford University Press.

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Summary Section 6.4 Before a cell divides, it copies all of its DNA (by DNA replication) so both of its cellular offspring inherit a complete set of chromosomes. For each molecule of DNA that is copied, two DNA molecules are produced; each is a duplicate of the parent. DNA replication is said to be semiconservative because one strand of each molecule is new, and the other is parental.

During DNA replication, enzymes unwind the double helix. Primers form and base-pair (hybridize) with the exposed single strands of DNA. Starting at the primers, DNA polymerase enzymes use each strand as a template to assemble new, complementary strands of DNA from free nucleotides. DNA ligase seals any gaps.

Proofreading by DNA polymerases corrects most DNA replication errors as they occur. DNA damage by environmental agents, including ionizing and nonionizing radiation, free radicals, and some chemicals, can lead to replication errors because DNA polymerase does not copy damaged DNA very well.

Most DNA damage is repaired before replication begins. uncorrected replication errors become mutations: permanent changes in the nucleotide sequence of a cell’s DNA.

Section 6.1 Somatic cell nuclear transfer (SCNT) and other types of reproductive cloning technologies produce genetically identical individuals (clones). ScNt works because the DNA in each body cell of an animal contains all the information necessary

to build a new individual. However, the outcome of ScNt is still unpredictable. this is because, during development, cells of an embryo become specialized as they begin to use different subsets of their DNA (a process called differentiation). reprogramming an adult cell to behave like an embryonic cell involves rewinding this developmental process, and we are still learning how to do it. cloning animals continues to raise ethical questions, particularly about the possibility of cloning humans.

Section 6.2 it took decades of research by many scientists to determine that deoxyribonucleic acid (DNA) is the hereditary material of all life, and to unravel its structure.

each DNA nucleotide has a five-carbon sugar, three phosphate groups, and one of four nitrogen-containing bases after which the nucleotide is named: adenine, thymine, guanine, or cytosine. DNA is a polymer that consists of two strands of these nucleotides coiled into a double helix. Hydrogen bonding between the internally positioned bases holds the strands together. the bases pair in a consistent way: adenine with thymine (A–t), and guanine with cytosine (G–c). the order of bases along a strand of DNA—the DNA sequence—varies among species and among individuals, and this variation is the basis of life’s diversity.

Section 6.3 the DNA of eukaryotes is divided among a characteristic number of chromosomes that differ in length and shape. in eukaryotic chromosomes, the DNA wraps around histones. When duplicated, a eukaryotic chromosome has an X shape and consists

of two sister chromatids attached at a centromere. Diploid cells have two of each type of chromosome.

Chromosome number is the sum of all chromosomes in a cell of a given species. A human body cell has twenty-three pairs of chromosomes. Members of a pair of sex chromosomes differ among males and females. chromosomes that are the same in males and females are autosomes. Autosomes of a pair have the same length, shape, and centromere location. A karyotype is an image of an individual’s complete set of chromosomes.

Answers in Appendix i

1. is an example of reproductive cloning. a. Somatic cell nuclear transfer (ScNt) b. Multiple offspring from the same pregnancy c. Artificial embryo splitting d. a and c e. all of the above

2. Which is not a nucleotide base in DNA? a. adenine c. glutamine e. cytosine b. guanine d. thymine f. All are in DNA.

3. What are the base-pairing rules for DNA? a. A–G, t–c c. A–t, G–c b. A–c, t–G d. A–A, G–G, c–c, t–t

4. Variation in is the basis of variation in traits. a. karyotype c. the double helix b. DNA sequence d. chromosome number

Self-Quiz

DNA StRUCtURe AND FUNCtioN ChAptER 6 111

1. Mutations are the original source of genetic variation. How can mutations accumulate in DNA, given that cells have repair sys- tems that fix mispaired nucleotides or breaks in DNA strands?

2. Woolly mammoths have been extinct for about 10,000 years, but we often find their well-preserved remains in Siberian permafrost. research groups are now planning to use ScNt to resurrect these huge elephant-like mammals. No mammoth eggs have been recovered so far, so elephant eggs would be used instead. An elephant would also be the surrogate mother for the resulting embryo. the researchers may try a modified ScNt technique used to clone a mouse that had been dead and frozen for sixteen years. ice crystals that form during freez- ing break up cell membranes, so cells from the frozen mouse were in bad shape. their DNA was transferred into donor mouse eggs, and cells from the resulting embryos were fused with mouse stem cells. Four healthy clones were born from the hybrid embryos. What are some of the pros and cons of cloning an extinct animal?

5. one species’ DNA differs from others in its . a. nucleotides d. replication process b. DNA sequence e. sugar–phosphate backbone c. double helix f. all of the above

6. in eukaryotic chromosomes, DNA wraps around . a. histone proteins c. centromeres b. sister chromatids d. nucleotides

7. chromosome number . a. refers to a particular chromosome in a cell b. is a characteristic feature of a species c. is the number of autosomes in cells of a given type d. is the same in all species

8. Human body cells are diploid, which means they . a. are complete b. have two sets of chromosomes c. contain sex chromosomes d. divide to form two cells

9. When DNA replication begins, . a. the two DNA strands unwind from each other b. the two DNA strands condense for base transfers c. old strands move to find new strands d. mutations occur

10. DNA replication requires . a. DNA polymerase c. primers b. nucleotides d. all are required

11. energy that drives the attachment of a nucleotide to the end of a growing strand of DNA comes from . a. phosphate-group transfers from AtP b. DNA polymerase c. the nucleotide itself d. a and c

12. After DNA replication, a eukaryotic chromosome . a. consists of two sister chromatids b. has a characteristic X shape c. is constricted at the centromere d. all of the above

13. exposure to can lead to mutations. a. uV light d. x-rays b. cigarette smoke e. sunlight c. chemicals f. all of the above

14. All mutations . a. arise from DNA damage c. are caused by radiation b. lead to evolution d. change the DNA sequence

15. Match the terms appropriately. nucleotide a. replication enzyme clone b. does not determine sex autosome c. copy of an organism DNA polymerase d. nitrogen-containing base, mutation sugar, phosphate bacteriophage e. injects DNA semiconservative f. can cause cancer replication g. something old, something new

1. Determine the complementary strand of DNA that forms on this template DNA fragment during replication:

G G T T T C T T C A A G A G A | | | | | | | | | | | | | | | _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

critical thinking

Visual Question

112

7.1 Ricin, RIP 114

7.2 Gene Expression 115

7.3 Transcription: DNA to RNA 116

7.4 The Genetic Code 118

7.5 Translation: RNA to Protein 119

7.6 Products of Mutated Genes 122

7.7 Control of Gene Expression 124

G e

n e

e x

p r

e s

s io

n a

n d

C o

n t

r o

112

114 Unit 2 GENETICs

7.1 Ricin, RIP REMEMBER: A fat consists mainly of triglycerides (section 2.8). A domain contributes a structural or functional property to a protein (2.9). A few strains of E. coli make a toxic protein that can severely damage the lining of the intestine (3.1). Ribosomes assemble polypeptides (3.4). Enzymes are unchanged by participating in a reaction (4.4). Cells can take in materials across their membrane by endocytosis (4.6).

Castor-oil plants grow wild in tropical regions, and they are widely cultivated for their seeds (Figure 7.1A). Castor-oil seeds are rich in ricin, a toxic protein that effec- tively deters beetles, birds, mammals, and other animals from eating them. They are also rich in castor oil, a fat that we extract from the seeds to use as an ingredient in plastics, cosmetics, paints, soaps, and many other items. Ricin-containing seed pulp left over from the extraction process is usually—but not always—discarded.

A dose of ricin as small as a few grains of salt can kill an adult human, and there is no antidote. Ricin’s lethal effect was known as long ago as 1888, but using it as a weapon is banned by most countries under the Geneva Protocol. Control- ling production of the toxin is impossible because no special skills or equipment are required to manufacture it from easily obtained raw materials. Thus, ricin appears periodically in the news as a tool of criminals. Perhaps the most famous example occurred in 1978 at the height of the Cold War, when defectors from countries under Russian control were targets for assassination. Bulgarian journalist Georgi Markov had defected to England and was working for the BBC. As he made his way to a bus stop on a London street, an assassin used a modified umbrella (Figure 7.1B) to fire a tiny pellet of ricin into Markov’s leg. Markov died in agony three days later.

Ricin is called a ribosome-inactivating protein (RIP) because it inactivates ribosomes, the organelles that assemble amino acids into proteins. Other RIPs are made by some bacteria, mushrooms, algae, and many plants (including food crops such as tomatoes, barley, and spinach). Most of these proteins are not particularly toxic in humans because they do not cross intact cell membranes very well. Those that do, including ricin, have a domain that binds to molecules on our plasma mem- branes. Binding causes the cell to take up the RIP by endocytosis. Once inside the cell, a second domain of the RIP—an enzyme—begins to inactivate ribosomes. One molecule of ricin can inactivate more than 1,000 ribosomes per minute. If enough ribosomes are affected, protein synthesis grinds to a halt. Proteins are critical to all life processes, so cells that cannot make them die quickly.

Fortunately, few people actually encounter ricin. Contact with other toxic RIPs is much more common. Bracelets made from beautiful seeds were recalled from stores in 2011 after a botanist recognized the seeds as jequirity beans. These beans contain abrin, an RIP even more toxic than ricin. Shiga toxin, an RIP made by Shigella dysenteriae bacteria, causes a severe bloody diarrhea (dysentery) that can be lethal. Some strains of E. coli make Shiga-like toxin, an RIP that causes symptoms associated with food poisoning.

Despite their toxicity, the main function of RIPs may not be destroying ribo- somes. Many are part of plant immunity, and have antiviral and anticancer activity. Plants that make toxic RIPs have been used as traditional medicines for many centu- ries; now, Western scientists are exploiting the unique properties of these proteins in drug design. For example, researchers have attached ricin’s toxic enzyme domain to antibodies that can find specific types of cancer cells in a person’s body. Other RIPs have also been modified to specifically target cancer cells (Figure 7.1C). The intent of both strategies: to assassinate the cancer cells without harming normal ones.

Figure 7.1 RiPs, examples of source and delivery. (A) Vaughan Fleming/SPL/Science Source; (B) Cary Wolinsky/National Geographic Creative; (C) Cheung et al. Molecular Cancer, 9:28, 2010.

Application

B. Bulgarian spy’s weapon: an umbrella modified to fire a tiny pellet of ricin into a victim. An umbrella like this one was used to assassinate Georgi Markov on the streets of London in 1978.

A. seeds of the castor-oil plant, source of ribosome- busting ricin. Eating just eight of these seeds can kill an adult human.

C. Researchers incorporated a peptide that binds to skin cancer cells into the enzy- matic domain of shiga-like toxin. The model shows the active site of the toxin in red; the changed bit, in blue. This engineered RIP specifically kills skin cancer cells.

GENE ExPREssIoN AND CoNTRoL ChAPtER 7 115

7.2 Gene Expression REMEMBER: Proteins are polymers of amino acids (section 2.9). The DNA in a body cell contains enough information to rebuild the individual (6.1). Information is encoded in the sequence of nucleotide bases in a DNA strand (6.2).

You learned in Chapter 6 that chromosomes are like a set of books that provide instructions for building and operating an individual. You already know the alphabet used to write those books: the four letters A, T, G, and C, for the four nucleotides in DNA—adenine, thymine, guanine, and cytosine. In this chapter, we investigate “words” that can be made from those letters, and “sentences” that can be made from the words.

The nature of information represented by the sequence of nucleotides in a DNA molecule occurs in hundreds or thousands of units called genes. The DNA sequence of a gene encodes (contains instructions for building) an RNA or protein product. Converting the information encoded by a gene into a product starts with RNA syn- thesis, which is called transcription. During transcription, enzymes use a strand of DNA as a template to assemble a strand of RNA.

Most of the RNA inside cells occurs in single strands that are similar in structure to single strands of DNA (Figure 7.2). For example, both are chains of four kinds of nucleotides. Like a DNA nucleotide, an RNA nucleotide has three phosphate groups, a sugar, and one of four bases. However, the sugar in an RNA nucleotide (ribose) is slightly different from the sugar in a DNA nucleotide (deoxy- ribose). Three bases (adenine, cytosine, and guanine) occur in both RNA and DNA nucleotides, but the fourth base differs between the two molecules. In DNA, the fourth base is thymine (T); in RNA, it is uracil (U). These small differences in structure give rise to very different functions. DNA’s important but only role is to store a cell’s genetic information. By contrast, a cell makes several kinds of RNAs on an ongoing basis, and the different types have different functions. Messenger RNA (mRNA) was named for its function as the “messenger” between DNA and protein. By the process of translation, the protein-building information in an mRNA is decoded (translated) into a sequence of amino acids. The result is a polypeptide that twists and folds into a protein.

Transcription and translation are both part of gene expression, the multistep process by which information in a gene guides the assembly of an RNA or protein product. Expression of a gene that encodes an RNA product (such as an mRNA) involves transcription. Expression of a gene that encodes a protein product involves both transcription and translation:

mRNADNA transcription

protein translation

gene A part of a chromosome that encodes an RNA or protein product in its DNA sequence.

gene expression Process by which the informa- tion in a gene guides assembly of an RNA or protein product. Includes transcription and translation.

messenger RnA (mRnA) RNA that has a protein- building message.

transcription Process by which enzymes assemble an RNA using a strand of DNA as a template.

translation Process by which the protein-building instructions in an mRNA guide the assembly of a polypeptide.

Take-Home Message 7.2 What is the nature of the information carried by DnA?

• Information in a DNA sequence occurs in units that are called genes. • A cell uses the information encoded by a gene to make an RNA or protein product, a

process called gene expression. • Transcription converts information in a gene to RNA; translation converts information

in an mRNA to protein.

Figure 7.2 Comparing DnA and RnA. DNA permanently stores a cell’s genetic information. Cells continually make different types of RNAs that have various functions.

DNA deoxyribonucleic acid

RNA ribonucleic acid

nucleotide base

base pair

sugar– phosphate backbone

116 Unit 2 GENETICs

7.3 Transcription: DNA to RNA REMEMBER: only two kinds of base pairings occur in DNA: G pairs with C, and A pairs with T (section 6.2). Each molecule of DNA produced during DNA replication is a duplicate of the parent (6.4).

The process of transcription is similar to DNA replication. Base-pairing rules are followed, for example. In DNA replication, cytosine (C) pairs with guanine (G), and adenine (A) pairs with thymine (T). The very same base-pairing rules also govern RNA synthesis in transcription, except that RNA, remember, has uracil instead of thymine (Figure 7.3). Uracil (U) base-pairs with adenine (A). During transcription, a strand of DNA acts as a template upon which a strand of RNA is assembled from nucleotides. A nucleotide can be added to a growing RNA only if it is complemen- tary to the corresponding nucleotide of the template DNA. As in DNA replication, each nucleotide provides the energy for its own attachment to the end of a grow- ing strand. Transcription is also similar to DNA replication in that one strand of a nucleic acid serves as a template for synthesis of another. However, in contrast to DNA replication, only part of one DNA strand, not the whole molecule, is used as a template for transcription. The enzyme RNA polymerase, not DNA polymerase, adds nucleotides to the end of a growing RNA. Also, transcription produces a single strand of RNA, not two DNA double helices.

In eukaryotic cells, transcription occurs in the nucleus; in prokaryotes, it occurs in cytoplasm. In both cases, the process begins at a regulatory site called a promoter, a short DNA sequence that serves as a binding site for RNA polymerase. Generally, a gene’s promoter is close to it and a bit upstream:

Binding at a promoter positions an RNA polymerase close to the gene that will be transcribed. The polymerase starts moving along the DNA, over the gene region.

RNA

DNA

T T TG GA AC C

A A AC CU UG G

A A AC CT TG G

T T TG GA AC C

RNA

DNA

T T TG GA AC C

A A AC CU UG G

A A AC CT TG G

T T TG GA AC C

Figure 7.3 Base pairing in DnA replication and RnA synthesis.

A. During DNA replication, a nucleotide is added to the end of a growing DNA strand only if it base- pairs with the corresponding nucleotide on the template DNA strand. Cytosine (C) pairs with gua- nine (G), and adenine (A) pairs with thymine (T).

B. During RNA synthesis, a nucleotide is added to the end of a growing RNA strand only if it base- pairs with the corresponding nucleotide on the template DNA strand. The same base-pairing rules apply, except that uracil in RNA base-pairs with adenine (A).

Figure 7.4 DnA Christmas trees. Typically, many RNA polymerases simultaneously transcribe the same gene, producing a structure called a Christmas tree after its shape. Here, several genes next to one another on the same chromo- some are being transcribed simultaneously. © O. L. Miller.

Figure it Out: Are the polymerases transcribing this DNA molecule moving from left to right or from right to left?

Answer: Left to right (the RNAs get longer as the polymerases move along the DNA)

DNA molecule RNA molecules a “Christmas tree”

promoter sequence in DNA

gene regionRNA polymerase

RNA

DNA unwindingDNA winding up

direction of transcription

T G

G T

C C

5�

GENE ExPREssIoN AND CoNTRoL ChAPtER 7 117

As it moves, the polymerase unwinds the double helix just a bit so it can “read” the nucleotide sequence of the template DNA strand:

An RNA polymerase moving over a gene region joins free RNA nucleotides into a chain, in the order dictated by the DNA sequence of the gene:

When the polymerase reaches the end of the gene region, it releases the DNA and the new RNA. The new RNA strand is complementary to the DNA strand from which it was transcribed. It is an RNA copy of a gene, in the same way that a paper transcript of a conversation carries the same information in a different format. Typically, many polymerases transcribe a particular gene region at the same time, so many new RNA strands can be produced very quickly (Figure 7.4).

RNA Modifications Just as a dressmaker may snip off loose threads or add bows to a dress before it leaves the shop, so do eukaryotic cells tailor their RNA before it leaves the nucleus. Consider that most eukaryotic genes contain intervening sequences called introns. Introns are removed in chunks from a newly transcribed RNA before it leaves the nucleus. Sequences that remain in the RNA after this pro- cess are called exons (Figure 7.5). Exons can be rearranged and spliced together in different combinations, so one gene may encode two or more versions of the same product. A newly transcribed RNA that will become an mRNA is further tailored after splicing. For example, a tail of 50 to 300 adenines is added to the end of a new mRNA. Among other functions, this poly-A tail is a signal that allows an mRNA to be exported from the nucleus.

exon Nucleotide sequence that remains in an RNA after post-transcriptional modification.

intron Nucleotide sequence that intervenes between exons and is removed during post-transcriptional modification.

promoter DNA sequence that is a site where RNA polymerase binds for transcription.

RnA polymerase Enzyme that carries out transcription.

Take-Home Message 7.3 how is RnA assembled?

• During transcription, RNA polymerase uses a gene region in a chromosome as a template to assemble a strand of RNA. The new strand is an RNA copy of the gene from which it was transcribed.

• Post-transcriptional modification of RNA occurs in the nucleus of eukaryotes.

transcription

gene

exon intron exon intron exon

exon

exon exon exon

intron exon intron exon

DNA

newly transcribed RNA

finished mRNA

promoter

poly-A tail

Figure 7.5 Post-transcriptional modification of RnA. Introns are removed and exons spliced together. Messen- ger RNAs also get a poly-A tail.

transcription

RNA processing

gene

exon intron exon intron exon

exon

exon exon exon

intron exon intron exon

DNA

new transcript

finished RNA

promoter

cap poly-A tail

5� 3�

transcription

RNA processing

gene

exon intron exon intron exon

exon

exon exon exon

intron exon intron exon

DNA

new transcript

finished RNA

promoter

cap poly-A tail

5� 3�finished mRNA

new RNA

DNA

An mRNA is a copy of a gene, in the same way that a paper transcript of a conversation carries the same information in a different format.

promoter sequence in DNA

gene regionRNA polymerase

RNA

DNA unwindingDNA winding up

direction of transcription

T G

G T

C C

5�

promoter sequence in DNA

gene regionRNA polymerase

RNA

DNA unwindingDNA winding up

direction of transcription

T G

G T

C C

5�

118 Unit 2 GENETICs

7.4 The Genetic Code REMEMBER: A polypeptide is a linear sequence of amino acids joined by peptide bonds (section 2.9).

An mRNA is essentially a disposable copy of a gene; its job is to carry the gene’s protein-building information to types of RNA during translation. The protein-building message is encoded by nucleotides, “genetic words” that occur one after another along its length. Like the words of a sentence, a series of these genetic words can form a meaningful parcel of informa- tion—in this case, the sequence of amino acids of a protein.

Each of the genetic “words” carried by an mRNA is three nucleotide bases long, and each is a code—a codon—for a particular amino acid. The sequence of bases in a triplet determines which amino acid the codon specifies (Figure 7.6A). For instance, the codon UUU codes for the amino acid phenylalanine (phe), and UUA codes for leucine (leu).

Codons occur one after another along the length of an mRNA. When the mRNA is translated, the order of its codons determines the order of amino acids in the resulting polypeptide. Thus, the DNA sequence of a gene is transcribed into the nucleotide sequence of an mRNA, which is in turn translated into an amino acid sequence:

A ACCT T TG G

A A AC CT T TG G

A ACCU U UG GA

met tyr ser

a gene region in DNA

mRNA

transcription

translation

protein

codoncodon codon

With four possible bases (G, A, U, or C) in each of the three positions of a codon, there are a total of sixty-four (or 43) mRNA codons. Collec- tively, the sixty-four codons constitute the genetic code. These codons specify a total of twenty naturally occurring amino acids (Figure 7.6B), so some amino acids have more than one codon. For instance, the amino acid tyrosine (tyr) is specified by two codons: UAU and UAC.

Other codons signal the beginning and end of a protein-coding sequence. In eukaryotes, the first AUG in an mRNA usually serves as the signal to start translation. AUG is the codon for methionine, so methio- nine is the first amino acid in new polypeptides. The codons UAA, UAG, and UGA do not specify an amino acid. These are signals that stop trans- lation, so they are called stop codons. A stop codon marks the end of the protein-coding sequence in an mRNA.

Figure 7.6 the genetic code.

Figure it Out: Which codons specify the amino acid lysine (lys)?

Answer: AAA and AAG

U C A

second base third base

first base

UUU

UUC

UUA

UUG

CUU

CUC

CUA

CUG

phe

ser

leu

UAU

UAC

UAA

UAG

tyr

stopstop

stop

UGU

UGC

UGA

UGG

cys

trp

UCU

UCC

UCA

UCG

asn

lys

GUU

GUC

GUA

GUG

val

GCU

GCC

GCA

GCG

ala

AUU

AUC

AUA

AUG

ile

met

ACU

ACC

ACA

ACG

thr

CCU

CCC

CCA

CCG

CAU

CAC

CAA

CAG

pro

CGU

CGC

CGA

CGG

arg

GGU

GGC

GGA

GGG

gly

AAU

AAC

AAA

AAG

his

gln

asp

glu

GAU

GAC

GAA

GAG

ser

arg

AGU

AGC

AGA

AGG

ala alanine (A)

arg arginine (R)

asn asparagine (N)

asp aspartic acid (D)

cys cysteine (C)

glu glutamic acid (E)

gln glutamine (Q)

gly glycine (G)

his histidine (H)

ile isoleucine (I)

leu leucine (L)

lys lysine (K)

met methionine (M)

phe phenylalanine (F )

pro proline (P)

ser serine (S)

thr threonine (T)

trp tryptophan (W)

tyr tyrosine (Y)

val valine (V)

A. Codon table. Each codon in mRNA is a set of three nucleotide bases. The left column lists a codon’s first base, the top row lists the second, and the right column lists the third.

sixty-one of the triplets encode amino acids; one of those, AUG, both codes for methionine and serves as a signal to start transla- tion. Three codons are signals that stop translation.

B. Names and abbreviations of the 20 naturally occurring amino acids specified by the genetic code (A).

GENE ExPREssIoN AND CoNTRoL ChAPtER 7 119

The genetic code is highly conserved, which means that most organisms use the same code and probably always have. Bacteria, archaea, and some protists have a few codons that differ from the eukaryotic code, as do mitochondria and chloro- plasts—a clue that led to a theory of how these two organelles evolved (we return to this topic in Section 13.3).

7.5 Translation: RNA to Protein REMEMBER: Ribosomes are organelles that carry out protein synthesis. some enzymes are RNAs (section 4.4).

A ribosome has two subunits, one large and one small (Figure 7.7). Each subunit consists mainly of ribosomal RNA (rRNA), with associated structural proteins. During translation, a large and a small ribosomal subunit converge as an intact ribo- some on an mRNA. Transfer RNAs (tRNAs) then deliver amino acids to the intact ribosome. Ribosomal RNA is one example of RNA with enzymatic activity: During translation, the rRNA components of a ribosome (not the protein components) cause peptide bonds to form between amino acids.

Each tRNA has two attachment sites. The first is an anticodon, which is a triplet of nucleotides that base-pairs with an mRNA codon (Figure 7.8). The other attachment site binds to an amino acid—the one specified by the codon. Transfer RNAs with different anticodons carry different amino acids. During translation, these tRNAs deliver amino acids to a ribosome, one after another in the order speci- fied by the codons in an mRNA. As the amino acids are delivered, the ribosome joins them via peptide bonds into a new polypeptide. Thus, the order of codons in an mRNA—DNA’s protein-building message—is translated into a new protein.

anticodon In a tRNA, set of three nucleotides that base-pairs with an mRNA codon.

codon In an mRNA, a nucleotide base triplet that codes for an amino acid or stop signal during translation.

genetic code Complete set of sixty-four mRNA codons.

ribosomal RnA (rRnA) RNA that becomes part of ribosomes.

transfer RnA (tRnA) RNA that delivers amino acids to a ribosome during translation.

Take-Home Message 7.4 What is the genetic code?

• The genetic code consists of sixty-four codons (base triplets). • Three codons are signals that stop translation; the remaining codons specify an amino

acid. In eukaryotic mRNAs, the first occurrence of the codon that specifies methionine is a signal to begin translation.

large subunit small subunit intact ribosome

Figure 7.7 Ribosome structure. An intact ribosome consists of a large and a small subunit. Protein components of both sub- units are shown in the ribbon models in green; rRNA components, in brown.

Figure 7.8 tRnA structure. Each tRNA’s anticodon is complementary to an mRNA codon. Each also carries the amino acid specified by that particular codon. These models depict the tRNA that car- ries the amino acid tryptophan.

CCA

trp

anticodon

amino acid attachment site

120 Unit 2 GENETICs

In all cells, translation occurs in cytoplasm. In a eukaryotic cell, RNAs that carry out transcription are produced in the nucleus (Figure 7.9

), then trans- ported through nuclear pores into cytoplasm

. Translation is initiated when ribo- somal subunits and tRNAs converge on an mRNA

. The complex of molecules is now ready to carry out protein synthesis. The intact ribosome begins to move along the mRNA and assemble a polypeptide

. The first tRNA carries the amino acid methionine, the first amino acid of the

new polypeptide. Another tRNA joins the complex when its anticodon base-pairs with the second codon in the mRNA. This tRNA brings with it the second amino acid. The ribosome joins the first two amino acids by way of a peptide bond:

Figure 7.9 Overview of translation in a eukaryotic cell. In eukaryotes, RNAs are transcribed in the nucleus, then transported into cytoplasm. Translation begins when ribosomal subunits and tRNA converge on an mRNA in cytoplasm. Then, tRNAs deliver amino acids in the order dictated by successive codons in the mRNA. The ribo- some links the amino acids together as it moves along the mRNA, so a polypeptide forms and elongates.

C C

leu

A A

C A

val

C A

C C

gly

GG GA AU U U U

CAU

G G

CC A UA A

CAU CAC

GG GA AU U G GU U

CC A

GG GA AU U G GU U

GG GA AU U GU U

AA U CC C

GGG GA AU U G GU U

AA U

GG GA AU U G GU U G GG C

initiator tRNA

first amino acid of polypeptide

start codon (AUG)

met val

peptide bond

met val leu

met

met val

metval val leu

leu gly

met

Transcription

RNA transport

mRNA

tRNA

ribosome subunits

Convergence of RNAs

Translation

polypeptide

GENE ExPREssIoN AND CoNTRoL ChAPtER 7 121

Take-Home Message 7.5 how is mRnA translated into protein?

• Translation is an energy-requiring process in which a polypeptide is synthesized based on the sequence of codons in an mRNA.

• During elongation, amino acids are delivered to the ribosome by tRNAs in the order dictated by successive mRNA codons. As amino acids arrive, the ribosome joins each to the end of the polypeptide.

C C

leu

A A

C A

val

C A

C C

gly

GG GA AU U U U

CAU

G G

CC A UA A

CAU CAC

GG GA AU U G GU U

CC A

GG GA AU U G GU U

GG GA AU U GU U

AA U CC C

GGG GA AU U G GU U

AA U

GG GA AU U G GU U G GG C

initiator tRNA

first amino acid of polypeptide

start codon (AUG)

met val

peptide bond

met val leu

met

met val

metval val leu

leu gly

met

C C

leu

A A

C A

val

C A

C C

gly

GG GA AU U U U

CAU

G G

CC A UA A

CAU CAC

GG GA AU U G GU U

CC A

GG GA AU U G GU U

GG GA AU U GU U

AA U CC C

GGG GA AU U G GU U

AA U

GG GA AU U G GU U G GG C

initiator tRNA

first amino acid of polypeptide

start codon (AUG)

met val

peptide bond

met val leu

met

met val

metval val leu

leu gly

met

The first tRNA is released and the ribosome moves to the next codon. Another tRNA brings the third amino acid to the ribosome as its anticodon base-pairs with the third codon of the mRNA. The ribosome joins the second and third amino acids by way of a peptide bond:

The second tRNA is released and the ribosome moves to the next codon. Another tRNA brings the fourth amino acid to the complex as its anticodon base- pairs with the fourth codon of the mRNA. The ribosome joins the third and fourth amino acids by way of a peptide bond:

The new polypeptide continues to elongate as the ribosome joins successive amino acids delivered by tRNAs. Translation ends when the ribosome reaches a stop codon in the mRNA. The mRNA and the polypeptide detach from the ribo- some, and the ribosomal subunits separate from each other.

Most of the energy that fuels translation is provided by GTP, an RNA nucleo- tide. Phosphate-group transfers from GTP help the ribosome move from one codon to the next along an mRNA. The RIPs you learned about in Section 7.1 are toxic because they remove a particular adenine base from one of the rRNAs in the ribo- some’s large subunit. The adenine is part of a binding site for proteins involved in the GTP-requiring steps of elongation. After the base has been removed, the ribo- some can no longer bind to these proteins, and elongation stops.

122 Unit 2 GENETICs

Figure 7.10 Examples of mutations. (A) 1BBB, A third quaternary structure of human hemoglobin A at 1.7-A resolution. Silva, M.M., Rogers, P.H., Arnone, A., Journal: (1992) J.Biol.Chem. 267: 17248–17256.

7.6 Products of Mutated Genes REMEMBER: Hydrophilic substances dissolve easily in water; hydrophobic substances do not (section 2.4). Hemoglobin has multiple polypeptides that fold around hemes; fibrous proteins such as keratin aggregate by many thousands into much larger structures (2.9). Many proteins can function properly only with assistance from a cofactor (4.4). A diploid cell has two sets of chromosomes (6.3). A mutation is a permanent change in the DNA sequence of a cell’s chromosome (6.4).

Mutations are relatively uncommon events in a normal cell. Consider that the chromosomes in a diploid human cell collectively consist of about 6.5 billion nucleotides, any of which may become mutated each time that cell divides. However, the mutation rate in human somatic cells is about 10-8, which means only one nucleotide changes every 108 times DNA replication occurs in these cells, on average. On top of that, less than 2 percent of human DNA encodes products, so there is an extremely low probability that any mutation will occur in a coding region. When a nucleotide in a protein-coding region does change, the redundancy of the genetic code offers the cell a margin of safety. For example, a mutation that changes a codon from CCU to CCC may have no further effect, because both of these codons specify proline.

Very rarely, a mutation changes an amino acid in a protein, or results in a premature stop codon that shortens it. Such mutations can have dras- tic effects on an organism. Consider hemoglobin, an oxygen-transporting protein in your red blood cells. Hemoglobin’s structure allows it to bind and release oxygen. In adult humans, a hemoglobin molecule consists of four polypeptides called globins: two alpha globins and two beta globins (Figure 7.10A). Each globin folds around a cofactor called heme. Oxygen molecules bind to hemoglobin at those hemes.

As red blood cells circulate through the lungs, the hemoglobin inside of them bind to oxygen molecules. The cells then travel to other regions of the body, and the hemoglobin releases its oxygen cargo wherever the oxygen level is low. When the red blood cells return to the lungs, the hemoglobin binds to more oxygen.

Mutations that alter hemoglobin’s structure can greatly impact health. For example, mutations in either the alpha or beta globin genes can cause a condition called anemia, in which a person’s blood is deficient in red blood cells or in hemoglobin. Both outcomes limit the blood’s ability to carry oxygen, and the resulting symptoms can range from mild to life- threatening. Sickle-cell anemia arises because of a particular mutation in the beta globin gene. The mutation changes one nucleotide to another, so it is called a base-pair substitution. In this case, the substitution results in a version of beta globin that has valine instead of glutamic acid as its sixth amino acid (Figure 7.10B,C). Hemoglobin assembled with this altered beta globin chain is called sickle hemoglobin, or HbS.

Unlike glutamic acid, which carries a negative charge, valine carries no charge. As a result of that one base-pair substitution, a tiny patch of the beta globin polypeptide that is normally hydrophilic becomes hydro- phobic. This change slightly alters the behavior of hemoglobin. Under certain conditions, HbS molecules stick together and form large, rodlike

C C U

UG G G GA A A

20 21 22 23 24 25 26 27 28 29 3019181716

pro glu glu lys ser

pro glu glu lys val

pro val glu lys ser

pro gly arg ser leu

C C U

UG G G GA A A

20 21 22 23 24 25 26 27 28 29 3019181716

pro glu glu lys ser

pro glu glu lys val

pro val glu lys ser

pro gly arg ser leu

C C U

UG G G GA A A

20 21 22 23 24 25 26 27 28 29 3019181716

pro glu glu lys ser

pro glu glu lys val

pro val glu lys ser

pro gly arg ser leu

C C U

UG G G GA A A

20 21 22 23 24 25 26 27 28 29 3019181716

pro glu glu lys ser

pro glu glu lys val

pro val glu lys ser

pro gly arg ser leu

C. A base-pair substitution replaces a thymine with an adenine. When the altered mRNA is translated, valine replaces glutamic acid as the sixth amino acid. Hemoglobin with this form of beta globin is called Hbs , or sickle hemoglobin.

D. A base-pair deletion shifts the reading frame for the rest of the mRNA, so a completely different protein product forms. The mutation shown results in a defective beta globin. The outcome is beta thalas- semia, a genetic disorder in which a person has an abnormally low amount of hemoglobin.

B. Part of the DNA (blue), mRNA (brown), and amino acid sequence of human beta globin. Numbers indicate nucleotide position in the mRNA.

A. Hemoglobin, an oxygen-binding protein in red blood cells. This protein consists of four polypeptides: two alpha globins (blue) and two beta globins (green). Each globin forms a pocket that cradles a cofactor called a heme (red). oxygen gas binds to the iron atom at the center of each heme.

E. An insertion of one nucleotide causes the reading frame for the rest of the mRNA to shift. The protein translated from this mRNA is too short and does not assemble correctly into hemoglobin mol- ecules. As in D, the outcome is beta thalassemia.

GENE ExPREssIoN AND CoNTRoL ChAPtER 7 123

base-pair substitution Mutation in which a single base pair changes.

deletion Mutation in which one or more nucleotides are lost.

insertion Mutation in which one or more nucleotides become inserted into DNA.

clumps. Red blood cells that contain the clumps become distorted into a crescent (sickle) shape (Figure 7.11). Sickled cells clog tiny blood vessels, thus disrupting blood circulation throughout the body. Over time, repeated episodes of sickling can damage organs and eventually cause death.

A different type of anemia called beta thalassemia is caused by a deletion, which is a mutation in which one or more nucleotides is lost from the DNA. In this case, the twentieth nucleotide in the coding region of the beta globin gene is lost (Figure 7.10D). Like most other deletions, this one causes the reading frame of the mRNA codons to shift. A frameshift usually has drastic consequences because it garbles the genetic message, just as incorrectly grouping a series of letters garbles the meaning of a sentence:

The fat cat ate the sad rat. T hef atc ata tet hes adr at. Th efa tca tat eth esa dra t.

The frameshift caused by the beta globin deletion results in a polypeptide that is very different from normal beta globin in amino acid sequence and in length. This outcome is the source of the anemia. Beta thalassemia can also be caused by an insertion, which is a mutation in which nucleotides are added to the DNA. Inser- tions, like deletions, often cause frameshifts (Figure 7.10E).

Some mutations can affect a gene’s expression without changing any of its codons. Special nucleotide sequences in DNA affect the expression of nearby genes. A promoter is one example; an intron–exon splice site is another. Consider a muta- tion that causes the hairless appearance of sphynx cats (Figure 7.12). In this case, a base-pair substitution disrupts an intron–exon splice site in a gene for keratin, a fibrous protein. The intron is not correctly removed during post-transcriptional processing. The altered protein translated from the resulting mRNA cannot prop- erly assemble into filaments that make up hair. Cats that have this mutation still make hair, but it falls out before it gets very long.

Take-Home Message 7.6 What happens after a gene becomes mutated?

• Mutations that change a protein can have drastic consequences on an organism’s form and function.

• A base-pair substitution may change an amino acid in a protein, or it may introduce a premature stop codon.

• Frameshifts that occur after an insertion or deletion can change an mRNA’s codon reading frame, thus garbling its protein-building instructions.

Figure 7.11 A sickled red blood cell compared with a normal one. A single base-pair substitution gives rise to an abnormal beta globin chain that, when assembled in hemoglobin molecules, forms Hbs. The sixth amino acid in these abnormal beta globin chains is valine, not glutamic acid. In the body, the difference causes Hbs molecules to form rod-shaped clumps that distort normally round blood cells (red) into the sickle shape (tan) characteristic of sickle-cell anemia. sickled cells clog small blood vessels. EM Unit, UCL Medical School, Royal Free Campus/Wellcome Images.

Figure 7.12 A sphynx cat. The hairless appearance of a sphynx cat arises from a single base-pair mutation in a gene for keratin, a fibrous protein that makes up hair. The altered keratin that results from the mutation does not assemble correctly into filaments. sphynx cats are not truly hairless; they produce hair, but it is easily dislodged. Glennis Siverson/National Geographic Creative.

Barr body Inactivated x chromosome in a cell of a female mammal. The other x chromosome is active.

knockout An experiment in which a gene is deliber- ately inactivated in a living organism; also, an organ- ism that has a knocked-out gene.

master gene Gene encoding a product that affects the expression of many other genes.

transcription factor Protein that influences transcrip- tion by binding to DNA.

124

7.7 Control of Gene Expression REMEMBER: Free radicals are dangerous to life (section 2.2). Estrogen and testos- terone are steroid hormones that govern reproduction and secondary sexual traits in animals (2.8). Bacteria can produce ATP by breaking down sugars in fermentation (5.6). As cells in an embryo start using different subsets of their DNA, they become different in form and function, a process called differentiatiation (6.1). The DNA of eukaryotic cells wraps around histones; body cells of human females typically have two x chromosomes (6.3).

A typical cell in your body uses only about 10 percent of its genes at a time. Some of the active genes affect structures and metabolic pathways common to all cells; others are expressed only by certain subsets of cells. For example, most body cells express genes that encode the enzymes of glycolysis, but only immature red blood cells express globin genes. Differentiation occurs as different cell lineages begin to express different subsets of their genes during development. Which genes a cell uses determines the molecules it will produce, which in turn determines what kind of cell it will be. Thus, control over gene expression is necessary for proper devel- opment of complex, multicelled bodies. It also allows individual cells to respond appropriately to changes in their internal and external environments.

All steps of gene expression are regulated, starting with transcription and ending with delivery of an RNA or protein product to its final destination in the cell. The “switches” that turn a gene on or off are molecules or processes that affect individual steps of its expression. For example, proteins called transcription factors affect whether and how fast a gene is transcribed by binding directly to the DNA. Some transcription factors prevent RNA polymerase from attaching to a gene’s pro- moter, which in turn prevents the gene’s transcription. Others help RNA polymerase bind to a promoter, which speeds up transcription. The rest of this section intro- duces some specific examples of gene expression control in eukaryotes.

Master Genes As an animal embryo develops, its cells differentiate and form tissues, organs, and body parts. The entire process of development is driven by cas- cades of master gene expression. The products of master genes affect the expres- sion of many other genes. Expression of a master gene causes other genes to be expressed, which in turn cause other genes to be expressed, and so on.

Gene expression that orchestrates animal development begins when differ- ent maternal mRNAs are delivered to different regions of cytoplasm in an egg as it forms. These mRNAs are translated only after the egg is fertilized. Then, their protein products diffuse away, forming gradients that span the developing embryo. The position of a cell within the embryo determines how much of these proteins it is exposed to. This in turn determines which master genes it turns on. The products of those master genes also form in gradients that diffuse away from cells expressing them. Still other master genes are transcribed depending on where a cell falls within these gradients, and so on. Eventually, the products of master genes cause undiffer- entiated cells to differentiate and become specialized.

A homeotic gene is a type of master gene whose expression directs the for- mation of a specific body part such as an eye, leg, or wing. Most homeotic genes encode transcription factors, and the function of many of them has been discovered by deliberately manipulating the genes’ expression (Figure 7.13). For example, in a common experiment called a knockout, researchers inactivate a gene by introduc- ing a mutation that prevents its expression, or by deleting it entirely. A knockout

A. A model of the protein product (in gold) of the homeotic gene anten- napedia attached to a promoter. Expression of antennapedia in embryonic tissues of the insect thorax causes legs to form.

B. The head of a normal fruit fly (left) has two antennae. Right, a mutation that triggers expression of the antenna- pedia gene in embryonic tissues of the head causes legs to form instead of antennae.

antenna leg

Figure 7.13 Example of a homeotic gene. Most homeotic genes, including this one, encode tran- scription factors that work by binding directly to DNA. (B) left, © Jürgen Berger, Max-Planck-Institute for Developmental Biology, Tübingen; right, Science VU/Dr. F. Rudolph Turner/Visuals Unlimited, Inc.

Which genes a cell uses determines the molecules it will produce, which in turn determines what kind of cell it will be.

GENE ExPREssIoN AND CoNTRoL ChAPtER 7 125

organism (one that has had a gene knocked out) may differ from normal individu- als, and the differences are clues to the function of the missing gene product.

Homeotic genes control development by the same mechanisms in all multi- celled eukaryotes, and many are interchangeable among different species. Thus, we can infer that they evolved in the most ancient eukaryotic cells. Consider the eyeless gene. Eyes form in embryonic fruit flies wherever this gene is expressed, which is normally in tissues of the head only. Flies with a mutated eyeless gene lack eyes (Fig- ure 7.14A). If the eyeless gene is expressed in another part of the developing embryo, eyes form there too (Figure 7.14B). Humans, squids, mice, fishes, and many other animals have a gene called PAX6, which is very similar in DNA sequence to the eye- less gene of flies. In humans, mutations in PAX6 cause eye disorders such as aniridia, in which the irises are underdeveloped or missing (Figure 7.14C). If a PAX6 gene from a human or a mouse is inserted into a fly, it has the same effect as the eyeless gene: An eye forms wherever it is expressed. (Because PAX6 is just a switch, the eye that forms is a fly eye, not a human or mouse eye.) The same principle applies in reverse: The eyeless gene from flies switches on eye formation in frogs. Such studies are evidence of shared ancestry among these evolutionarily distant animals.

Sex Chromosome Genes In humans and other mammals, a female’s cells have two X chromosomes, one inherited from her mother, the other one from her father. In each cell, one X chromosome is always tightly condensed (Figure 7.15). We call the condensed X chromosomes Barr bodies, after Murray Barr, who discovered them. Condensation inhibits transcription, so most of the genes on a Barr body are not expressed. This X chromosome inactivation ensures that only one of the two X chromosomes in a female’s cells is active, thus equalizing expression of X chro- mosome genes between the sexes—a mechanism called dosage compensation. The body cells of male mammals (XY) have one set of X chromosome genes. Body cells of female mammals (XX) have two sets, but female embryos do not develop prop- erly when both sets are expressed.

At this writing, researchers have discovered 1,805 genes on the human X chro- mosome. Only a few of them are associated with traits that differ between males and females; most govern nonsexual traits such as blood clotting and color perception. The Y chromosome has only 458 known genes, but one of them is SRY—the master gene for male sex determination in mammals. Its expression in XY embryos triggers the formation of testes, which are male reproductive organs. Some of the cells in tes- tes make testosterone, a steroid hormone that controls the emergence of male sec- ondary sexual traits such as facial hair, increased musculature, and deepened voice. We know that SRY is the master gene that controls emergence of male sexual traits because mutations in this gene cause XY individuals to develop external genitalia that appear female. An XX embryo has no Y chromosome, no SRY gene, and much less testosterone, so primary female reproductive organs (ovaries) form instead of testes. Ovaries make estrogens and other sex hormones that will govern the devel- opment of female secondary sexual traits, such as enlarged, functional breasts, and fat deposits around the hips and thighs.

Lactose Tolerance Humans and other mammals break down lactose, a carbo- hydrate in milk, but most do so only when young. An individual’s ability to digest lactose ends at a certain age that depends on the species. In the majority of humans worldwide, this switch occurs at about age five, when transcription of the gene for lactase slows. The resulting decline in production of the enzyme causes a common condition known as lactose intolerance.

C. A normal human eye has a colored iris surrounding the pupil (dark area where light enters). Mutations in PAX6 cause eyes to develop without an iris, a condition called aniridia.

B. Eyes form wherever the eyeless gene is expressed in fly embryos—here, on the head and also on the wing.

The PAX6 gene of humans, mice, squids, and some other animals is so similar to eye- less that it similarly triggers eye development in fruit flies.

A. A normal fruit fly (left) has large, round eyes. A fruit fly with a mutation in its eyeless gene (right) develops without eyes.

eye

eyeless

Figure 7.14 Eyes and eyeless. (A) David Scharf/Science Source; (B) Eye of Science/Science Source; (C) left, M. Bloch; right, Courtesy of the Aniridia Foundation International, www.aniridia.net.

Figure 7.15 X chromosome inactivation. Barr bodies are visible as red spots in the nucleus of the four xx cells on the left. Compare the nucleus of two xY cells to the right. © Dr. William Strauss.

126 Unit 2 GENETICs

Cells in the intestinal lining secrete lactase into the small intestine, where the enzyme cleaves lactose into its monosaccharide monomers. Monosaccharides are absorbed directly by the small intestine, but lactose is not. Thus, when lactase production slows, lactose consumed in food passes undigested through the small intestine. The lactose ends up in the large intestine, which hosts huge numbers of bacteria. These cells respond to the presence of lactose by switching on genes that break it down. Carbon dioxide and other gaseous products of their various fermen- tation reactions accumulate quickly in the large intestine, distending its wall and causing pain. Other products of their metabolism disrupt the solute–water balance inside the large intestine, and diarrhea results.

Not everybody is lactose intolerant. About one-third of human adults carry a mutation that allows them to digest milk; this mutation is more common in some populations than in others. Recent analyses of DNA from well-preserved skeletons show that the vast majority of adult humans living about 8,000 years ago in Europe were lactose intolerant (Figure 7.16). Around that time, a mutation appeared in the DNA of prehistoric people inhabiting a region between what is now central Europe and the Balkans. This mutation allowed its bearers to continue digesting milk as adults, and it spread rapidly to the rest of the continent along with the practice of dairy farming. Today, most adults of northern and central European ancestry are able to digest milk because they carry this mutation, a single base-pair substitution in a region of DNA that helps control the lactase gene promoter. Other mutations in the same region of DNA arose independently in North Africa, southern Asia, and the Middle East. Some people descended from these populations can continue to digest milk as adults.

DNA Methylation In a eukaryotic cell, only regions of DNA that have been unwound from histones are accessible to RNA polymerase for transcription. Modifi- cations to histone proteins change the way they interact with DNA wrapped around them, thus affecting transcription. Some modifications make histones release their grip on DNA; others make them tighten it. For example, adding methyl groups (—CH3) to a histone tightens the DNA around it, so enzymes that methylate his- tones can slow or shut down transcription.

Direct methylation of DNA nucleotides also suppresses transcription, often more permanently than histone modifications. Once a particular nucleotide has become methylated in a cell’s DNA, it will usually stay methylated in the DNA of the cell’s descendants. Methylation and other heritable modifications to DNA that affect its function but do not alter the nucleotide sequence are said to be epigenetic.

DNA methylation is a part of differentiation, so it begins very early in embry- onic development: Genes actively expressed in a zygote (the first cell of a new individual) become silenced as their promoters get methylated. This silencing is the basis of selective gene expression that drives differentiation. During development, and also during the remainder of the individual’s life, each cell’s DNA continues to acquire methylations. Between 3 and 6 percent of the DNA has been methylated in a normal, differentiated body cell.

Methyl groups are usually added to a cytosine that is followed by a guanine (Figure 7.17), but which of these cytosines get methylated varies by the individual. This is because methylation is influenced by environmental factors. For instance, humans conceived during a famine end up with an unusually low number of methyl groups in the DNA of certain genes. The product of one of those genes is a hormone that promotes prenatal growth and development. The resulting increase in expres- sion of this gene may offer a survival advantage in a poor nutritional environment. Figure 7.17 DnA methylation.

Figure 7.16 Milk wasn’t on the Stone Age menu. South Tyrol Museaum of Archaeology/A. Ochsenreiter, as altered by Lisa Starr.

C NH

CC N

N NH2

P O

O OCH2

NH2

C N

C OHC N

O OCH2

CH3

cytosine

guanine

A. In the DNA of differentiated cells, a methyl group (red) is most often attached to a cytosine (C) that is followed by a guanine (G).

B. A model of DNA shows methyl groups (red) attached to a cytosine–guanine pair on complementary DNA strands. When the cytosine on one strand is methylated, enzymes methylate the cytosine on the other strand. This is why a methylation tends to persist in a cell’s descendants.

The vast majority of adult humans living about 8,000 years ago in Europe were lactose intoler- ant. Today, about one-third of human adults carry a mutation that allows them to digest milk.

GENE ExPREssIoN AND CoNTRoL ChAPtER 7 127

epigenetic Refers to heritable changes in gene expression that are not the result of changes in DNA sequence.

Take-Home Message 7.7 how is gene expression controlled?

• Gene expression can be switched on or off, or speeded or slowed, by molecules and processes that operate at each step.

• This control allows cells to respond appropriately to environmental change. It is also critical for differentiation and development in multicelled eukaryotes.

• Epigenetic modifications of DNA acquired during an individual’s lifetime can be passed to offspring, so gene expression patterns can persist for generations.

Nucleotides also become methylated by chance during DNA replication, so cells that divide a lot tend to have more methyl groups in their DNA than inactive cells. Free radicals and toxic chemicals add more methyl groups.

Factors that influence DNA methylation can have multigenerational effects. When an organism reproduces, it passes its DNA to offspring. Methylation of parental DNA is normally “reset” in the zygote, with new methyl groups being added and old ones being removed. This reprogramming does not remove all of the parental methyl groups, however, so some methylations acquired during an indi- vidual’s lifetime are passed to future offspring. Inheritance of epigenetic modifica- tions can adapt offspring to an environmental challenge much more quickly than evolution (we return to evolutionary processes in Chapter 12). Epigenetic modifica- tions are not considered to be evolutionary because the underlying DNA sequence does not change. Even so, they may persist for generations after an environmental challenge has faded.

Effect of Grandmother’s Food Supply on infant Mortality

Researchers are investigating long-reaching epigenetic effects of starvation, in part because historical data on periods of famine are widely available. Before the industrial revolution, a failed harvest in one autumn typically led to severe food shortages the following winter. A retrospective study has correlated female infant mortality at certain ages with the abundance of food during the paternal grandmother’s childhood. Figure 7.18 shows some of the results of this study.

1. Compare the mortality risk of girls whose paternal grandmothers ate well at age 2 with that of girls whose grandmothers were starv- ing at the same age. Which girl was more likely to die early? About how much more likely was she to die?

2. Children have a period of slow growth around age 9. What trend in this data can you see around that age?

3. There was no correlation between early death of a male child and eating habits of his paternal grandmother, but there was a strong correlation with the eating habits of his paternal grandfather. What does this tell you about the probable location of epigenetic changes that gave rise to these data?

Figure 7.18 An epigenetic effect. The graph shows relative risk of early death of a female child correlated with the age at which her paternal grandmother experienced a winter with a food supply that was scarce (blue) or abundant (red) during childhood. The dotted line represents no difference in risk of mortality. A value above the line means an increased risk; one below the line indicates a reduced risk. Source: Pembrey et al., European Journal of Human Genetics (2006) 14, 159–166.

Digging Into Data

Factors that influence DNA methylation can have multi- generational effects.

Age of paternal grandmother (years)

scarce

Abundant

M or

ta lit

y ris

k ra

tio o

f f em

al e

ch ild

0.5

1.0

2.0

4 6 8 10 12 14 16 18 200 2

128

Summary Section 7.1 the ability to make proteins is critical to all life processes. ricin and other ribosome-inactivating proteins (rips) have an enzyme domain that alters ribosomes, thus destroying the cell’s ability to make proteins. a cell that cannot make proteins dies quickly.

Section 7.2 information encoded within the nucleotide sequence of dna occurs in subsets called genes. Gene expression is the conversion of information in a gene to an rna or protein product. rna is produced during transcription. during translation, protein- building information in an mRNA (messenger RNA) is converted into a sequence of amino acids in a polypeptide:

Section 7.3 during transcription, RNA polymerase binds to a promoter near a gene region in a chromosome, then links rna nucleotides in the order dictated by the nucleotide base sequence of the dna strand. the resulting rna strand is an rna

copy of the gene. in eukaryotes, rna is modified before it leaves the nucleus. Intron sequences are removed, and the remaining exon sequences may be rearranged and spliced in different combinations. Messenger rnas are further modified.

Section 7.4 an mrna ’s protein-building information consists of a series of codons, sets of three nucleotides. all sixty-four codons, most of which specify amino acids, constitute the genetic code.

Section 7.5 each tRNA (transfer RNA) has an anticodon that can base-pair with a codon, and it binds to the amino acid specified by that codon.

proteins and enzymatic rRNA (ribosomal RNA) make up the two subunits of a ribosome. during translation, codons in an mrna direct synthesis of a polypeptide. First, the mrna, a trna, and two ribosomal subunits converge. next, successive amino acids are delivered by trnas in the order specified by the codons in the mrna. the ribosome causes a peptide bond to form between the amino acids as they arrive, so a polypeptide forms. translation ends when the ribosome encounters a stop codon in the mrna.

Section 7.6 Insertions, deletions, and base-pair substitutions are mutations. a mutation that changes a gene’s product may have harmful effects. in humans, an example is sickle-cell anemia, a disorder caused by a single base-pair substitution in the gene for the beta

globin chain of hemoglobin.

Section 7.7 Gene expression control is the basis of cell differentiation in multicelled eukaryotes, and it also allows individual cells to respond to changes in their environment. Molecules and processes that influence gene expression operate at every step

between transcription and delivery of the gene product to its final destination. proteins called transcription factors influence transcription by binding directly to dna.

all cells of an embryo share the same genes; different cells in it become specialized as they begin to use different subsets of those genes, a pro cess called differentiation. Various master genes are expressed locally in different parts of the developing embryo. their products, which diffuse through the embryo in gradients, affect expression of other master genes, which in turn affect the expression of others, and so on. Cells differentiate according to their exposure to these gradients. eventually, master gene expression induces the expression of homeotic genes, the products of which trigger development of specific body parts. the function of many homeotic genes was revealed by knockouts.

in cells of female mammals, one of the two x chromosomes is condensed as a Barr body. the condensation makes most of this chromosome’s genes permanently inaccessible. in humans, the SRY gene determines male sex. a mutation that abolishes control over expression of the lactase gene allows some people to continue digesting milk in adulthood.

dna modifications (such as methylations) that affect gene expression but do not involve changes to the dna sequence are said to be epigenetic. an individual acquires these modifications during its lifetime, as a consequence of cell division and also by exposure to environmental challenges. epigenetic modifications are passed to the cell’s descendants; some have multigenerational effects because they can be passed to the individual’s offspring.

Answers in Appendix i

1. a chromosome contains many genes that are transcribed into different . a. proteins c. rnas b. polypeptides d. a and b

2. rnas form by ; proteins form by . a. replication; translation b. translation; transcription c. transcription; translation d. replication; transcription

mRNADNA transcription

protein translation

RNA

DNA

T T TG GA AC C

A A AC CU UG G

A A AC CT TG G

T T TG GA AC C

RNA

DNA

T T TG GA AC C

A A AC CU UG G

A A AC CT TG G

T T TG GA AC C A ACCT T TG G

A A AC CT T TG G

A ACCU U UG GA

met tyr ser

a gene region in DNA

mRNA

transcription

translation

protein

codoncodon codon

self-Quiz

GENE ExPREssIoN AND CoNTRoL ChAPtER 7 129

1. an anticodon has the sequence GCG. What amino acid does this trna carry? What would be the effect of a mutation that changed the C of the anticodon to a G?

2. each position of a codon can be occupied by one of four (4) nucleotides. What is the minimum number of nucleotides per codon necessary to specify all 20 of the naturally occurring amino acids that are assembled into proteins?

3. Why are some genes expressed and some not?

4. Bacteria use the same stop codons as eukaryotes. However, bacterial transcription is also terminated in places where the mrna folds back on itself to form a hairpin-looped structure like the one shown on the right. How do you think that this struc- ture stops transcription?

3. in cells, most rna molecules are , and dna molecules are . a. single-stranded; double-stranded b. double-stranded; single-stranded

4. the main function of an mrna molecule is to . a. store heritable information b. carry a translatable message c. form peptide bonds between amino acids

5. Where does transcription take place in a eukaryotic cell? a. the nucleus c. the cytoplasm b. ribosomes d. b and c are correct

6. What is the maximum number of amino acids that can be encoded by a gene with 45 bases plus a stop codon? a. 15 c. 90 b. 45 d. 135

7. Most codons specify a(n) . a. protein c. amino acid b. polypeptide d. mrna

8. Where does translation take place in a eukaryotic cell? a. the nucleus c. the cytoplasm b. ribosomes d. b and c are correct

9. a mutation called a often results in a frameshift that garbles the genetic message. a. deletion c. base-pair substitution b. insertion d. a and b

10. Muscle cells differ from bone cells because . a. they carry different genes c. they are eukaryotic b. they use different genes d. both a and b

11. the expression of a gene may depend on . a. the type of organism c. the type of cell b. environmental conditions d. all of the above

12. a gene that is knocked out is . a. deleted c. expressed b. inactivated d. either a or b

13. a cell with a Barr body is . a. prokaryotic c. from a female mammal b. a sex cell d. infected by Barr virus

14. true or false? some gene expression patterns are heritable.

15. put the following processes in order of their occurrence during expression of a eukaryotic gene: a. mrna processing c. transcription b. translation d. rna leaves nucleus

16. Match each term with the most suitable description. methylation a. cells become specialized insertion b. cascades of control promoter c. can be epigenetic genetic message d. assembles amino acids differentiation e. read in threes SRY f. makes a man out of you master gene g. extra nucleotides ribosome h. binding site for rna polymerase

1. Use Figure 7.6 to translate the following sequence of bases in an mrna into an amino acid sequence, starting at the first base. Use the one-letter abbreviations for the amino acids.

GGUGaaaaUGaGaCCaUUUGUaGU 2. translate the base sequence in the previous question, starting

at the second base.

Critical thinking

Visual Question

8.1 Henrietta’s Immortal Cells 132

8.2 Multiplication by Division 133

8.3 Mitosis and Cancer 137

8.4 Sex and Alleles 140

8.5 Meiosis in Sexual Reproduction 142

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132 Unit 2 GenetICS

Application

Cells are individually alive, even as part of a multicelled body.

8.1 Henrietta’s Immortal Cells Each human starts out as a fertilized egg. By the time of birth, that single cell has given rise to about a trillion other cells, all organized as a human body. Even in the adult, billions of cells divide every day as new cells replace worn-out ones. However, despite the ability of human cells to continue dividing as part of a body, they tend to divide a limited number of times when grown in the laboratory. As early as the mid-1800s, researchers were trying to coax human cells to keep dividing outside of the body because they realized immortal cell lineages—cell lines—would allow them to study human diseases (and potential cures) without experimenting on people. The quest to create a human cell line continued unsuccessfully until 1951. By this time, George and Margaret Gey had been trying to culture human cells for nearly thirty years. Then their assistant, Mary Kubicek, prepared a new sample of human cancer cells. Mary named the cells HeLa, after the first and last names of the patient from whom the cells had been taken. The HeLa cells began to divide, again and again. The cells were astonishingly vigorous, quickly coating the inside of their test tube and consuming their nutrient broth. Four days later, there were so many

cells that the researchers had to transfer them to more tubes. The cell populations increased at a phenomenal rate. The cells were dividing every twenty-four hours and coating the inside of the tubes within days.

Sadly, cancer cells in the patient were dividing just as fast. Only six months after she had been diagnosed with cervi- cal cancer, malignant cells had invaded tissues throughout her body. Two months after that, Henrietta Lacks, a young woman from Baltimore, was dead.

Even after Henrietta had passed away, her cells lived on in the Geys’ laboratory. The Geys discovered how to grow polio- virus in HeLa cells, a practice that enabled them to determine

which strains of the virus cause polio. That work was a critical step in the development of polio vaccines, which have since saved millions of lives.

Henrietta Lacks was just thirty-one, a wife and mother of five, when runaway cell divisions of cancer killed her. Her cells, however, are still dividing, again and again, more than sixty years after she died. Frozen away in tiny tubes packed in Styrofoam boxes, HeLa cells continue to be shipped among laboratories all over the world. They are still widely used to investigate cancer (Figure 8.1), viral growth, protein synthesis, the effects of radiation, and countless other processes important in medicine and research. HeLa cells helped several researchers win Nobel Prizes, and they even traveled into space for experiments on satellites.

Understanding why cancer cells are immortal—and why we are not—begins with learning about the structures and mechanisms that cells use to divide.

Figure 8.1 HeLa. this micrograph shows two dividing cells of the HeLa line—cellular legacy of cancer victim Henrietta Lacks (left). Blue and green tracers identify the location of proteins that help attach chromosomes (white) to microtubules (red) during the division process. the

location of the proteins is abnormal, which means the chromosomes are not properly attached to microtubules that are supposed to distribute them evenly into descen- dant cells. Defects in these and other proteins that orches- trate cell division result in cells with too many or too few chromosomes, an outcome associated with cancer. Top, Dr. Paul D. Andrews/University of Dundee; inset, courtesy of the family of Henrietta Lacks.

HOW CELLs REpROduCE Chapter 8 133

inte rphase

G2 prophase

metaphase

anaphase

telophase mitosis

cytoplasmic division

mmmm

inte rphase

it i

8.2 Multiplication by Division reMeMBer: processes by which individuals produce offspring are called reproduc- tion (section 1.3). Microtubules consist of tubulin subunits; microfilaments form a cell cortex that reinforces the plasma membrane; a rigid cell wall surrounds the plasma membrane of a plant cell; the motor protein myosin interacts with microfila- ments to bring about contraction (3.5). When a phosphate group is transferred from ATp, energy is transferred along with it (4.4). sister chromatids attach to one another at the centromere (6.3). A cell copies its chromosomes by dNA replication (6.4).

A life cycle is a sequence of recognizable stages that occur during an organism’s lifetime, from the first cell of the new individual until its death. Multicelled organ- isms and free-living cells have life cycles, but what about cells that make up a multicelled body? Biologists consider such cells to be individually alive, each with its own lifetime. A cell’s life passes through a series of recognizable intervals and events collectively called the cell cycle (Figure 8.2). A typical body cell spends most of its life in interphase

. During interphase, the cell increases its mass, roughly doubles the number of its cytoplasmic components, and copies its chromosomes in preparation for division. Interphase has three major stages: G1, S, and G2. G1 and G2 were named “Gap” phases because outwardly they seem to be periods of inactiv- ity, but they are not. Most cells going about their metabolic business are in G1

. Cells preparing to divide enter S

, when they undergo DNA replication. During G2 4

, cells make the proteins that will carry out division. The rest of the cell cycle consists of the division process itself. When the cell

divides, both of its two cellular offspring end up with a blob of cytoplasm and some DNA. Each of the offspring of a eukaryotic cell inherits its DNA packaged inside a nucleus. Thus, a eukaryotic cell’s nucleus has to divide before its cytoplasm does. Mitosis is a nuclear division mechanism that maintains the chromosome num- ber 5

. In multicelled organisms, mitosis and cytoplasmic division 6

are the basis of increases in body size and tissue remodeling during development, as well as ongoing replacements of damaged or dead cells in the adult. Mitosis and cyto- plasmic division are also part of asexual reproduction, a reproductive mode by which offspring are produced by one parent only. Some multicelled eukaryotes and many single-celled ones use this mode of reproduction. (Prokaryotes do not have a nucleus and do not undergo mitosis. We discuss their reproduction in Section 13.5.)

Figure It Out: Each of the embryos in the photo con- sists of how many cells? answer: Eight

Figure 8.2 the eukaryotic cell cycle. The photo shows early frog embryos, each a product of three mitotic divisions of one fertilized egg.

A cell spends most of its life in interphase, which includes three stages: G1, s, and G2.

G1 is the phase of growth before dNA replication. The cell’s chromosomes are unduplicated.

s is the phase of synthesis, during which the cell makes copies of its chromosome(s) by dNA replication.

G2 is the phase after dNA replication and before mitosis. The cell prepares to divide during this stage.

The nucleus divides during mitosis.

After mitosis, the cytoplasm may divide. Each descendant cell begins the cycle anew, in interphase.

Built-in checkpoints stop the cycle from proceeding until certain conditions are met (see section 8.3).

Carolina Biological Supply Company/ Phototake.

asexual reproduction Reproductive mode of eukary- otes by which offspring arise from a single parent.

cell cycle The collective series of intervals and events of a cell’s life, from the time it forms until it divides.

interphase In a eukaryotic cell cycle, the interval between mitotic divisions when a cell grows, roughly doubles the number of its cytoplasmic components, and replicates its dNA.

mitosis Nuclear division mechanism that maintains the chromosome number.

134

When a cell divides by mitosis, it produces two descendant cells, each with the chromosome number of the parent. However, if only the total number of chro- mosomes mattered, then one of the descendant cells might get, say, two pairs of chromosome 22 and no chromosome 9. A cell cannot function properly without a full complement of DNA, which means it needs to have a copy of each chromo- some. Thus, the two cells produced by mitosis have the same number and types of chromosomes as the parent. Figure 8.3 shows how mitosis maintains the chromo- some number. Consider how your body’s cells are diploid, which means their nuclei contain pairs of chromosomes—two of each type. One chromosome of a pair was inherited from your father; the other, from your mother. Except for a pairing of nonidentical sex chromosomes (XY) in males, the chromosomes of each pair are homologous. Homologous chromosomes have the same length, shape, and genes (hom– means alike). When a cell is in G1, each of its chromosomes consists of one double-stranded DNA molecule. The cell replicates its DNA in S, so by G2, each of its chromosomes consists of two double-stranded DNA molecules. These molecules stay attached to one another at the centromere as sister chromatids until mitosis is almost over, and then they are pulled apart and packaged into two separate nuclei. When sister chromatids are pulled apart, each becomes an individual chromosome that consists of one double-stranded DNA molecule. Thus, each of the two new nuclei that form in mitosis contains a full complement of chromosomes. When the cytoplasm divides, these nuclei are packaged into separate cells. Each new cell has the parental chromosome number, and starts its life in G1 of interphase.

Figure 8.4 shows the details of mitosis. When a cell is in interphase, its chromo- somes are loosened to allow transcription and DNA replication. Loosened chro- mosomes are spread out, so they are not easily visible under a light microscope

. In preparation for nuclear division, the chromosomes begin to pack tightly

. Transcription and DNA replication stop as the chromosomes condense into their most compact “X” forms. Tight condensation keeps the chromosomes from getting tangled and breaking during nuclear division. A cell reaches prophase, the first stage of mitosis, when its chromosomes have condensed so much that they are visible under a light microscope

. “Mitosis” is from mitos, the Greek word for thread, after the threadlike appearance of the chromosomes during nuclear division.

Also during prophase, microtubules assemble and extend from two regions on opposite sides of the cell. These microtubules form a spindle, a temporary struc- ture that moves chromosomes during nuclear division. The spindle penetrates the nuclear region as the nuclear envelope breaks up. Some of the microtubules stop lengthening when they reach the middle of the cell. Others lengthen until they reach a chromosome and attach to it at the centromere. By the end of prophase, one sister chromatid of each chromosome has become attached to microtubules extending from one end of the cell, and the other sister has become attached to microtubules extending from the other end.

The opposing sets of microtubules then begin a tug-of-war by adding and losing tubulin subunits. As the microtubules lengthen and shorten, they push and pull the chromosomes. When all the microtubules are the same length, the chromo- somes are aligned in the middle of the cell

. The alignment marks metaphase. During anaphase, the sister chromatids of each duplicated chromosome separate, so each becomes an individual, unduplicated chromosome. The spindle moves the chromosomes toward opposite sides of the cell

. Telophase begins when the two clusters of chromosomes reach opposite ends

of the cell 6

. Each cluster has the same number and kinds of chromosomes as the parent cell nucleus had: two of each chromosome, if the parent cell was diploid.

Figure 8.3 How mitosis maintains the chromosome number in a diploid cell. For clarity, only one pair of homologous chromosomes is illustrated. pink indicates a chromosome of maternal origin; blue, a chromosome of paternal origin.

C. Mitosis and cytoplasmic division package one copy of each chromosome into each of two new cells.

a. pair of homologous chromosomes in a cell during G1.

B. By the end of G2, each chromosome has been duplicated, so it has two sister chromatids.

anaphase Stage of mitosis during which sister chro- matids separate and move toward opposite spindle poles.

homologous chromosomes In the nucleus of a diploid eukaryotic cell, chromosomes with the same length, shape, and set of genes.

metaphase Stage of mitosis at which all chromo- somes are aligned in the middle of the cell.

prophase Stage of mitosis during which chromo- somes condense and become attached to a newly forming spindle.

spindle temporary structure that moves chro- mosomes during nuclear division; consists of microtubules.

telophase Stage of mitosis during which chromo- somes arrive at opposite ends of the cell. two new nuclei form as the chromosomes loosen.

HOW CeLLS RepRODuCe CHapter 8 135

Figure 8.4 Mitosis. Micrographs show nuclei of plant cells (onion root, left), and animal cells (fertilized egg of a roundworm, right). A diploid (2n) animal cell with two chromosome pairs is illustrated. Plant cell nuclei, Michael Clayton/University of Wisconsin, Department of Botany; animal cell nuclei, © ISM/Phototake.

early prophase

Mitosis begins. transcription stops, and the DnA begins to appear grainy as it starts to condense.

interphase

Interphase cells are shown for comparison, but inter- phase is not part of mitosis. the red spots in the plant cell nucleus are areas where ribosome subunits are being transcribed and assembled.

prophase

the duplicated chromosomes become visible as they condense. the nuclear envelope breaks up. Spindle microtubules assemble and bind to chromosomes at the centromere. Sister chromatids become attached to microtubules extending from opposite ends of the cell.

Metaphase

All of the chromosomes are aligned in the middle of the cell.

anaphase

Spindle microtubules separate the sister chromatids and move them toward opposite sides of the cell. each sister chromatid has now become an individual, unduplicated chromosome.

telophase

the chromosomes reach opposite sides of the cell and loosen up. Mitosis ends when a new nuclear envelope forms around each cluster of chromosomes.

Mitosis in an animal cellMitosis in a plant cell

spindle

nuclear envelope breaking up

136 Unit 2 GenetICS

A new nucleus forms around each cluster as the chromosomes loosen up again, after which telophase—and mitosis—are finished.

Cytoplasmic Division In most eukaryotes, the cell cytoplasm divides between late anaphase and the end of telophase, so two cells form, each with their own nucleus. The mechanism of cytoplasmic division differs between plants and animals.

Typical animal cells pinch themselves in two after nuclear division ends (Fig- ure 8.5). How? The cell cortex, which is the mesh of cytoskeletal elements just under the plasma membrane, includes a band of microfilaments and motor proteins that wraps around the cell’s midsection. The band is called a contractile ring because it contracts when the motor proteins are energized by phosphate-group transfers from ATP. Contraction occurs after telophase, when the spindle disassembles

. Because the contractile ring is attached to the plasma mem- brane, it pulls the membrane inward as it contracts

. The sinking plasma membrane is visible on the outside of the cell as an indentation (left), which is called a cleavage furrow

. The cleavage furrow advances around the cell and deepens until

the cytoplasm—and the cell —is pinched in two 4

. Each of the two cells formed by this division has its own nucleus and some of the parent cell’s cytoplasm, and each is enclosed by a plasma membrane.

Dividing plant cells face a particular challenge because a stiff cell wall sur- rounds their plasma membrane. Accordingly, plant cells have their own mechanism of cytoplasmic division (Figure 8.6). By the end of anaphase, a set of short microtu- bules has formed on either side of the future plane of division. These microtubules now guide vesicles from Golgi bodies and the cell surface to the division plane

. There, the vesicles and their wall-building contents start to fuse into a disk-shaped cell plate

. The plate expands at its edges until it reaches the plasma membrane and attaches to it, thus partitioning the cytoplasm

. In time, the cell plate will develop into two new cell walls, so each of the descendant cells will be enclosed by its own plasma membrane and wall

Figure 8.5 Cytoplasmic division of an animal cell.

Figure 8.6 Cytoplasmic division of a plant cell.

Take-Home Message 8.2 How do eukaryotic cells reproduce?

• A eukaryotic cell reproduces by division: nucleus first, then cytoplasm. • Mitosis (a nuclear division mechanism that maintains the chromosome number) and

cytoplasmic division are part of the cell cycle, a series of events and stages through which a cell passes during its lifetime.

• DnA replication occurs before mitosis begins, so each chromosome consists of two DnA molecules attached as sister chromatids.

• During mitosis, a spindle assembles, then separates all of the sister chromatids and moves them to opposite sides of the cell. A new nuclear envelope forms around each of the two clusters of chromosomes. the two new nuclei have the same chromosome number as the parent cell.

1 In a dividing animal cell, the spindle dis- assembles as mitosis ends.

the ring contracts until it pinches the cell in two.

this contractile ring pulls the cell surface inward as it shrinks. the indentation is called a cleavage furrow.

2 At the midpoint of the former spindle, a ring of actin and myosin filaments attached to the plasma mem- brane contracts.

Vesicles containing wall- building materials cluster at the future plane of divi- sion before mitosis ends.

the vesicles fuse with each other, forming a cell plate.

the cell plate expands to the plasma membrane. When it attaches to the membrane, it partitions the cytoplasm.

the cell plate matures as two new cell walls. these walls join with the parent cell wall, so each descendant cell becomes enclosed by its own wall.

HOW CeLLS RepRODuCe CHapter 8 137

8.3 Mitosis and Cancer reMeMBer: A receptor protein triggers a change in cell activity in response to a stimulus such as binding to a certain substance; adhesion proteins help cells stick together in animal tissues (Section 3.3). Dolly the sheep died early, most likely because she was a clone (6.1). An image of a cell’s chromosomes is a karyotype (6.3). proofreading and repair mechanisms usually maintain the integrity of a cell’s genetic information by correcting mispaired bases and fixing DnA damage (6.4). Gene expression can be switched on or off by molecules or processes that operate at each step; a knockout is an organism with a gene that has been deliberately inacti- vated (7.7).

When a cell divides—and when it does not—is determined by mechanisms of gene expression control. Like the accelerator of a car, some of these mechanisms cause the cell cycle to advance. Others are like brakes, preventing the cycle from proceed- ing. In the adult body, brakes on the cell cycle normally keep the vast majority of cells in G1. Most of your nerve cells, skeletal muscle cells, heart muscle cells, and fat-storing cells have been in G1 since you were born, for example.

Control over the cell cycle also ensures that a dividing cell’s descendants receive intact copies of its chromosomes. Built-in checkpoints ensure the cell’s DNA has been copied completely, that it is not damaged, and even that enough nutrients are available to support division (a few checkpoints are indicated in Figure 8.2). Protein products of “checkpoint genes” interact to carry out this control process. For example, a checkpoint that operates in S monitors whether the cell’s chromosomes have been damaged during DNA replication. Checkpoint proteins recognize dam- aged DNA and bind to it. This binding puts the brakes on the cell cycle, and also enhances expression of genes involved in DNA repair. After the damage has been fixed, the brakes are lifted and the cell cycle proceeds. If the DNA remains unre- paired, other checkpoint proteins trigger events that cause the cell to self-destruct.

Cell Division Gone Wrong Sometimes a checkpoint gene mutates so that its protein product no longer works properly. In other cases, the controls that regulate its expression fail, and a cell makes too much or too little of the gene’s product. When enough checkpoint mechanisms fail, a cell loses control over its cell cycle. Interphase may be skipped, so division occurs over and over with no resting period. Signaling mechanisms that cause abnormal cells to die may stop working. The problem is com- pounded because checkpoint malfunctions are inherited by the cell’s descendants, which form a neoplasm—an accumulation of abnormally dividing cells.

A neoplasm that makes a lump in the body is called a tumor, but the two terms are sometimes used interchangeably. Once a tumor-causing mutation has occurred, the gene it affects is called an oncogene. An oncogene is any gene that helps trans- form a normal cell into a tumor cell. Oncogene mutations in reproductive cells can be passed to offspring, which is a reason that some types of tumors run in families.

Not every gene can become an oncogene; those that can are called proto- oncogenes. Consider how most of your body cells have receptors for growth factors, which are molecules that stimulate cell division and differentiation. When a growth factor binds to its receptor on a cell, a series of events is triggered that advances the cell cycle from interphase into mitosis. Mutations can result in a receptor that stimulates mitosis even when the growth factor is not present, and in fact most neoplasms carry mutations resulting in an overactivity or overabundance of growth factor receptors (Figure 8.7).

cleavage furrow In a dividing animal cell, the inden- tation where cytoplasmic division will occur.

neoplasm An accumulation of abnormally dividing cells.

oncogene Gene that helps transform a normal cell into a tumor cell.

tumor A neoplasm that forms a lump.

Figure 8.7 an oncogene causing a neoplasm. In this section of human breast tissue, a brown-colored tracer shows the active form of a growth factor receptor. normal cells are lighter in color.

the dark cells have an overactive receptor that is con- stantly stimulating mitosis; these cells have formed a neoplasm. Cells of most neoplasms have mutations that cause this receptor to be overproduced or overactive. © From Expression of the epidermal growth factor receptor (EGFR) and the phosphorylated EGFR in invasive breast carcinomas. http://breast-cancer-research.com/content/10/3/R49.

138 Unit 2 GenetICS

Checkpoint gene products that inhibit mitosis are called tumor suppressors because tumors form when they are missing. Two examples are BRCA1 and BRCA2: Mutations in these genes give rise to neoplasms in the breast, prostate, ovary, and other tissues. The multiple functions of the BRCA gene products are still being unraveled, but we do know they help maintain the structure and number of chro- mosomes in a dividing cell, and they participate directly in DNA repair. BRCA gene products also bind to hormone receptors that are particularly abundant on cells of breast and ovarian tissues; the binding suppresses transcription of growth factor genes in these cells. When a mutation alters a BRCA gene so that its product cannot bind to these hormone receptors, the cells overproduce growth factors—an outcome associated with neoplasm formation.

Viruses such as HPV (human papillomavirus) cause a cell to make proteins that interfere with its own tumor suppressors. Infection with HPV causes skin growths called warts, and some kinds are associated with neoplasms that form on the cervix.

Cancer Benign neoplasms such as warts are not usually dangerous. They grow very slowly, and their cells retain the plasma membrane adhesion proteins that keep them properly anchored in their home tissue. A malignant neoplasm is one that gets progressively worse, and is dangerous to health. Malignant cells typically display the following three characteristics:

First, like cells of all neoplasms, malignant cells grow and divide abnormally. Controls that usually keep cells from getting overcrowded in tissues are lost in malig- nant cells, so their populations may reach extremely high densities with cell division occurring very rapidly. The number of small blood vessels that transport blood to the growing cell mass also increases abnormally.

Second, the cytoplasm and plasma membrane of malignant cells are altered. Both are indications of cellular malfunction. The cytoskeleton may be shrunken, disorganized, or both. Malignant cells typically have an abnormal chromosome number, with some chromosomes present in multiple copies, and others missing or damaged. The balance of metabolism is often shifted, as in an amplified reliance on ATP formation by fermentation rather than aerobic respiration.

Altered or missing proteins impair the function of the plasma membrane of malignant cells. For example, these cells do not stay anchored properly in tissues because their plasma membrane adhesion proteins are defective or missing. Malig- nant cells can slip easily into and out of vessels of the circulatory and lymphatic systems (Figure 8.8). By migrating through these vessels, the cells can establish neoplasms elsewhere in the body. The process in which malignant cells break loose from their home tissue and invade other parts of the body is called metastasis. Metastasis is the third hallmark of malignant cells.

The disease called cancer occurs when the abnormally dividing cells of a malignant neoplasm disrupt body tissues, both physically and metabolically. Unless chemotherapy, surgery, or another procedure eliminates malignant cells from the body, they can put an individual on a painful road to death. Each year, cancer causes 15 to 20 percent of all human deaths in developed countries. The good news is that mutations in multiple checkpoint genes are required to transform a normal cell into a malignant one, and such mutations may take a lifetime to accumulate. Lifestyle choices such as not smoking and avoiding exposure of unprotected skin to sunlight reduce one’s risk of acquiring mutations in the first place. Some neoplasms can be detected with periodic screening such as gynecology or dermatology exams (Figure 8.9). If detected early enough, many types of malignant neoplasms can be removed before metastasis occurs.

C. Melanoma spreads fastest. Cells form dark, encrusted lumps that may itch or bleed easily.

B. Squamous cell carcinoma is the second most common form of skin cancer. this pink growth, firm to the touch, grows under the skin’s surface.

a. Basal cell carcinoma is the most common type of skin cancer. this slow-growing, raised lump may be uncolored, reddish-brown, or black.

Figure 8.9 Skin cancer can be detected and treated early with periodic screening. (A) Dr. Allan Harris/Phototake; (B) Biophoto Associates/Science Source; (C) James Stevenson/ Science Source.

Figure 8.8 neoplasms and malignancy.

a. Benign neoplasms grow slowly and stay in their home tissue.

B. Cells of a malignant neoplasm can break away from their home tissue.

C. the malignant cells become attached to the wall of a lymph vessel or blood vessel (as shown here). they release digestive enzymes that create an opening in the wall, then enter the vessel.

D. the cells creep or tumble along in the vessel, then exit the same way they got in. Migrating cells may start grow- ing in other tissues, a process called metastasis.

HOW CeLLS RepRODuCe CHapter 8 139

HeLa Cells are a Genetic Mess

HeLa cells can vary in chromosome number. Defects in proteins that orchestrate cell division result in descen- dant cells with too many or too few chromosomes, an outcome that is one of the hallmarks of cancer cells. the karyotype in Figure 8.10, originally published in 1989, shows all of the chromosomes in a single meta- phase HeLa cell.

1. What is the chromosome number of this HeLa cell? 2. How many extra chromosomes does this cell have,

compared with a normal human body cell? 3. Can you tell that this cell came from a female? How? Figure 8.10 Karyotype of a HeLa cell.

Digging Into Data

cancer Disease that occurs when a malignant neoplasm physically and functionally disrupts body tissues.

metastasis the process in which cells of a malig- nant neoplasm spread from one part of the body to another.

Telomeres Remember that Dolly the cloned sheep died early. The life expectancy of a sheep is normally about 10 to 12 years; by the time Dolly was five, however, she was as fat and arthritic as a twelve-year-old sheep. The following year, she con- tracted a lung disease typical of much older sheep and had to be euthanized.

Dolly’s early demise may have been the result of abnormally short telomeres. Telomeres are noncoding DNA sequences that occur at the ends of eukaryotic chromosomes (Figure 8.11). Vertebrate telomeres consist of a short, noncoding DNA sequence repeated perhaps thousands of times. These “junk” repeats provide a buffer against the loss of more valuable DNA internal to the chromosomes.

A telomere buffer is particularly important because, under normal circum- stances, a eukaryotic chromosome shortens by about 100 nucleotides with each DNA replication. When a cell’s offspring receive chromosomes with too-short telomeres, checkpoint gene products halt the cell cycle, and the descendant cells die shortly thereafter. Most body cells can divide only a certain number of times before this happens. This cell division limit may be a fail-safe mechanism in case a cell loses control over the cell cycle and begins to divide again and again. A limit on the number of divisions keeps the resulting neoplasm from overrunning the body.

The cell division limit varies by species, and it may be part of the mechanism that sets an organism’s life span. Dolly’s DNA came from the nucleus of a mam- mary gland cell donated by an adult sheep. When Dolly was only two years old, her telomeres were as short as those of a six-year-old sheep—the exact age of the adult animal that had been her genetic donor.

A few normal cells in an adult retain the ability to divide indefinitely. These cells are called stem cells, and their descendants replace other cell lineages that eventually die out when they reach their division limit. Stem cells are immortal because they continue to make telomerase, an enzyme that reverses the telomere shortening asso- ciated with DNA replication (differentiated body cells produce no telomerase).

Mice that have had their telomerase enzyme knocked out age prematurely, with a life expectancy about half that of a normal mouse. When one of these knock- out mice is close to the end of its shortened life span, rescuing the function of its telomerase enzyme results in lengthened telomeres. The rescued mouse also regains

Figure 8.11 telomeres. the bright dots at the end of each DnA strand in these (duplicated) chromosomes are telomere sequences. © ISM/Phototakeusa.

140 Unit 2 GenetICS

8.4 Sex and Alleles reMeMBer: All organisms inherit their DnA from parents by processes of repro- duction (Section 1.3). traits shared by members of a species often vary a bit among individuals, as eye color does among people (1.4). A somatic cell is a body cell (6.1). DnA sequence variation is the basis of traits that define species and distinguish individuals (6.2). the two autosomes of a pair hold information about the same traits (6.3). Mutations (6.4) that alter a gene’s product can be harmful (7.6).

Your homologous chromosomes carry the same genes, but their DNA sequence may not be identical (Figure 8.12). This is because you inherited your chromo- somes from two parents who are, most likely, not closely related. Unique mutations accumulated in their separate lines of descent over time. Thus, the DNA sequence of any of your genes may differ a bit from the corresponding gene on the homologous chromosome. Different forms of the same gene are called alleles.

Alleles may encode slightly different forms of a gene’s product, and such dif- ferences influence the details of shared, inherited traits. Members of a species have the same traits because they have the same genes. However, almost every shared trait varies a bit among individuals of a sexually reproducing species. Alleles of the shared genes are the basis of this variation. Consider just one human gene, HBB, which encodes beta globin. HBB has has more than 700 alleles; a few cause sickle- cell anemia, several cause beta thalassemia, and so on. There are approximately 20,000 human genes, and most of them have multiple alleles.

On the Advantages of Sex You learned earlier in this chapter that mitosis and cytoplasmic division are part of asexual reproduction in eukaryotes, but only a few

Take-Home Message 8.3 What is cancer?

• Gene expression controls advance, delay, or block the cell cycle in response to internal and external conditions. Checkpoints built into the cell cycle allow problems to be cor- rected before the cycle proceeds.

• neoplasms form when cells lose control over their cell cycle and begin dividing abnormally.

• Mutations in multiple checkpoint genes can give rise to a progressively worsening malignant neoplasm.

• Cancer is a disease that occurs when the abnormally dividing cells of a malignant neoplasm physically and metabolically disrupt body tissues.

• In most cases, lifestyle choices and early intervention can reduce one’s risk of cancer.

vitality: Worn-out tissue in the brain and other organs repairs itself and begins to function normally, and the once-geriatric individual even begins to reproduce again.

Researchers are careful to point out that shortening telomeres may be an effect of aging rather than a cause. Also, while telomerase holds therapeutic promise for rejuvenating aged tissues, it can be dangerous. Cancer cells—including the HeLa cells you learned about in Section 8.1—characteristically express high levels of this molecule, which is why, like stem cells, they can divide indefinitely.

Figure 8.12 Genes on chromosomes. Different forms of a gene are called alleles. (A) Courtesy of Carl Zeiss MicroImaging, Thornwood, NY.

Genes occur in pairs on homologous chromosomes.

the members of each pair of genes may be identical, or they may differ slightly, as alleles. (Color varia- tions represent sequence differences.)

a. Corresponding colored patches in this fluores- cence micrograph indicate corresponding DnA sequences in a homolo- gous chromosome pair. these chromosomes carry the same set of genes.

B. Homologous chromo- somes carry the same series of genes, but the DnA sequence of any one of those genes might dif- fer just a bit from that of its partner on the homolo- gous chromosome.

HOW CeLLS RepRODuCe CHapter 8 141

species use this reproductive mode (Figure 8.13). Most eukaryotes reproduce sexu- ally. Sexual reproduction is the process in which offspring arise from two parents and inherit genes from both.

If the function of reproduction is the perpetuation of one’s genes, then an asexual reproducer would seem to win the evolutionary race. When it reproduces, it passes all of its genes to every one of its offspring. Only about half of a sexual repro- ducer’s genes are passed to each offspring. So why is sex so widespread?

All offspring of an asexual reproducer are clones: Barring new mutations, they have exactly the same alleles as their one parent. Consistency is a good evolution- ary strategy in a favorable, unchanging environment; alleles that help an organ- ism survive and reproduce in the environment do the same for its descendants. However, most environments are constantly changing, and change is not always favorable. Individuals that are identical are equally vulnerable to challenges. In a changing environment, sexual reproducers have the evolutionary edge because they carry different alleles. Sexual reproduction mixes up the genetic information of two parents that differ in the alleles they carry, so offspring typically inherit new combi- nations of alleles—ones that do not occur in either parent (or other offspring). Some may inherit a particular combination of alleles that suits them perfectly to a new environmental challenge. As a group, their diversity offers them a better chance of surviving environmental change than clones.

To understand why environments constantly change, think about one example: interactions between a predatory species and its prey. To the prey species, the preda- tors are an environmental challenge. Prey individuals that can best escape predation tend to leave more offspring, so alleles that help them be best tend to become more common in the species over generations. At the same time, prey that can better escape predation are an environmental challenge to the predator species. Predator individuals best able to capture prey tend to leave more offspring, so alleles that help them be best tend to become more common in the predator species over genera- tions (Chapter 12 returns to evolutionary processes). The two species are locked in a constant race, with each genetic improvement in one countered by a genetic improvement in the other. This idea is called the Red Queen hypothesis, a reference to Lewis Carroll’s book Through the Looking Glass. In the book, the Queen of Hearts tells Alice, “It takes all the running you can do, to keep in the same place.”

Another advantage of sexual reproduction involves the inevitable occurrence of mutations that are harmful but not lethal. A population of sexual reproducers has a better chance of weathering the effects of such mutations. With asexual reproduc- tion, individuals bearing a harmful mutation necessarily pass it to all of their off- spring. This outcome would be rare in sexual reproduction, because each offspring of a sexual union has a 50 percent chance of inheriting a parent’s mutation. Thus, all else being equal, harmful mutations can spread through an asexually reproducing population more quickly than a sexually reproducing one.

alleles Forms of a gene with slightly different DnA sequences; may encode slightly different versions of the gene’s product.

sexual reproduction Reproductive mode by which offspring arise from two parents and inherit genes from both.

Take-Home Message 8.4 Why do species that reproduce sexually vary in shared traits?

• paired genes on homologous chromosomes may vary in DnA sequence as alleles. Alleles arise by mutation.

• Alleles of shared genes are the basis of differences in traits shared by a species. • Offspring of sexual reproducers inherit new combinations of parental alleles.

Figure 8.13 tiny new Zealand mud snails can reproduce on their own (asexually) or with a partner (sexually). Like most sexual organisms, the sexual snails have two chromosome sets; like most animals that cannot reproduce sexually, the asexual snails have at least three. DnA has a high phosphorus content; having the extra sets of chromosomes multiplies each organism’s require- ment for this nutrient. Fertilizers and detergents contain phosphorus, so agricultural runoff and other types of water pollution may be fueling the gigantic populations of asexual snails currently invading ecosystems worldwide. © Bart Zijistra.

Almost every shared trait varies a bit among individuals of a sexually reproducing species.

142

lplasma membrane spindle

pair of homologous chromosomespair of homologous chromosomesnuclear envelope breaking up

plasma membrane pplasmaplasma membranemembranemembrane spindlespindlspindlespindle

nuclear envelope breaking upnuclear envelope breaking unuclear envelope breaking upnuclear envelope breaking up

haploid Having one of each type of chromosome characteristic of the species.

meiosis nuclear division process that halves the chromosome number. Basis of sexual reproduction.

lplasma membrane spindle

pair of homologous chromosomespair of homologous chromosomesnuclear envelope breaking up

plasma membrane pplasmaplasma membranemembranemembrane spindlespindlspindlespindle

nuclear envelope breaking upnuclear envelope breaking unuclear envelope breaking upnuclear envelope breaking up

prophase i Homologous chromosomes condense, pair up, and swap segments. Spindle micro- tubules attach to them as the nuclear envelope breaks up.

telophase i A complete set of chromo- somes clusters at both ends of the cell. A nuclear envelope forms around each set, so two haploid (n) nuclei form.

Metaphase i Homologous chromosome pairs are aligned between spindle poles. Spindle microtubules attach the two chromosomes of each pair to opposite spindle poles.

anaphase i All of the homolo- gous chromosomes separate and begin heading toward the spindle poles.

MeiOSiS i One diploid nucleus to two haploid nuclei

8.5 Meiosis in Sexual Reproduction Meiosis, a nuclear division mechanism that halves the chromosome number, is the process inherent to sexual reproduction that gives rise to new combinations of alleles in offspring. It parcels chromosomes into new nuclei two times (Figure 8.14 shows the stages of meiosis in a diploid (2n) cell). DNA replication occurs before meiosis begins, so each chromosome has two sister chromatids.

The first stage of meiosis I is prophase I 1

. During this phase, the chromo- somes condense, and homologous chromosomes align tightly and swap segments (more about segment-swapping shortly). The nuclear envelope breaks up. A spindle forms, and by the end of prophase I, microtubules attach one chromosome of each homologous pair to one spindle pole, and the other to the opposite spindle pole. These microtubules grow and shrink, pushing and pulling the chromosomes as they do. At metaphase I

, all of the microtubules are the same length, and the chro- mosomes are aligned midway between the spindle poles. During anaphase I

, the spindle pulls the homologous chromosomes of each pair away from one another

HOW CeLLS RepRODuCe CHapter 8 143

No DNA replication No DNA replication No DNA No DNANo DNA replicationreplicationreplication

Figure 8.14 Meiosis. the micrographs show meiosis in a lily cell. the illustra- tions show two pairs of chromosomes in a diploid (2n) animal cell; homologous chromosomes are indicated in blue and pink. Bottom photos, With thanks to the John Innes Foundation Trustees, computer enhanced by Gary Head.

No DNA replication No DNA replication No DNA No DNANo DNA replicationreplicationreplication

prophase ii the chromosomes condense. Spindle microtubules attach to each sister chromatid as the nuclear envelope breaks up.

Metaphase ii the (still duplicated) chromosomes are aligned midway between spindle poles.

anaphase ii Sister chromatids sepa- rate. the (now undupli- cated) chromosomes head to the spindle poles.

telophase ii A complete set of chromo- somes clusters at both ends of the cell. A new nuclear envelope forms around each set, so four haploid (n) nuclei form.

MeiOSiS ii two haploid nuclei to four haploid nuclei

answer: Anaphase I

Figure it Out: Which phase of meiosis reduces the chromosome number?

and toward opposite spindle poles. The two sets of chromosomes reach the spindle poles during telophase I

, and a new nuclear envelope forms around each cluster of chromosomes as the DNA loosens up. The two new nuclei are haploid (n); each contains one set of chromosomes—half of the diploid (2n) number. The cytoplasm often divides at this point. Each chromosome is still duplicated (it consists of two sister chromatids). Meiosis may pause at this point, but no DNA replication occurs before meiosis II.

Meiosis II proceeds simultaneously in both nuclei that formed in meiosis I. During prophase II

, the chromosomes condense and the nuclear envelope breaks up. A new spindle forms. By the end of prophase II, spindle microtubules attach each chromatid to one spindle pole, and its sister chromatid to the oppo- site spindle pole. These microtubules push and pull the chromosomes, aligning them midway between spindle poles at metaphase II

. During anaphase II 7

, the spindle microtubules pull the sister chromatids apart and toward opposite spindle poles. Each chromosome is now unduplicated (it consists of one molecule of DNA). During telophase II

, these chromosomes reach the spindle poles.

144 Unit 2 GenetICS

New nuclear envelopes form around the four clusters of chromosomes as the DNA loosens up. Each of the four nuclei that form are haploid (n), with one set of (unduplicated) chromosomes. The cytoplasm often divides at this point.

How Meiosis Mixes Alleles We mentioned briefly that duplicated chromo- somes swap segments with their homologous partners during prophase I. As the chromosomes condense, each is drawn close to its homologous partner, so that the chromatids align along their length:

This tight, parallel orientation favors crossing over, a process by which a chromo- some and its homologous partner exchange corresponding pieces of DNA during meiosis (Figure 8.15A–C). Homologous chromosomes may swap any segment of DNA along their length, although crossovers tend to occur more frequently in certain regions.

Swapping segments of DNA shuffles alleles between homologous chromo- somes. It breaks up the particular combinations of alleles that occurred on the parental chromosomes, and makes new ones on the chromosomes that end up in offspring. Thus, crossing over introduces novel combinations of alleles—and new combinations of traits—among offspring. It is a normal and frequent process in meiosis, but the rate of crossing over varies among species and among chromo- somes. In humans, between 46 and 95 crossovers occur per meiosis, so on average each chromosome crosses over at least once (Figure 8.15D).

From Gametes to Offspring Sexual reproduction involves the fusion of mature reproductive cells—gametes—from two parents. All gametes are haploid, and they arise by division of germ cells, which are immature reproductive cells that form in organs set aside for reproduction. Animals and plants make gametes somewhat dif- ferently. In animals, meiosis in diploid germ cells gives rise to eggs (female gametes) or sperm (male gametes). In plants, haploid germ cells form by meiosis. Gametes form when these cells divide by mitosis. We leave details of sexual reproduction in animals and plants for later chapters, but you will need to know a few concepts before you get there.

At fertilization, two haploid gametes fuse and produce a diploid zygote, which is the first cell of a new individual. Thus, meiosis halves the chromosome number, and fertilization restores it. If meiosis did not precede fertilization, the chromosome number would double with every generation. If the chromosome number changes, so does the individual’s set of genetic instructions. An individual’s set of chromo- somes is like a fine-tuned blueprint that must be followed exactly, in order to build a body that functions normally. As you will see in Chapter 9, chromosome number changes can have drastic consequences for health, particularly in animals.

Fertilization also contributes to the variation that we see among offspring of sexual reproducers. Think about it in terms of human reproduction. Cells that give rise to human gametes have twenty-three pairs of homologous chromosomes. Each time a human germ cell undergoes meiosis, the four gametes that form end up with one of 8,388,608 (or 223) possible combinations of homologous chromosomes. In

Figure 8.15 Crossing over. Blue signifies a paternal chromosome, and pink, its maternal homologue. For clarity, only one pair of homologous chromosomes is shown. (D) James Kezer/Courtesy of Dr. Sessions.

a. Here, we focus on only two of the many genes on a chromosome. In this example, one gene has alleles A and a; the other has alleles B and b.

B. Close contact between homologous chromosomes promotes crossing over between nonsister chromatids. paternal and maternal chromatids exchange corresponding pieces.

C. Crossing over mixes up paternal and mater- nal alleles on homolo- gous chromosomes.

D. each pair of homolo- gous chromosomes can cross over multiple times. this is a normal and com- mon process of meiosis.

B b

A A

centromere

crossover

HOW CeLLS RepRODuCe CHapter 8 145

Take-Home Message 8.5 How does meiosis give rise to new combinations of parental alleles among the offspring of sexual reproducers?

• During meiosis, the nucleus of a diploid (2n) cell divides twice. DnA replication does not occur between the two divisions, so the chromosome number is reduced to the haploid number (n) for forthcoming gametes.

• Crossing over—recombination between nonsister chromatids of homologous chro- mosomes—occurs during meiosis. It makes new combinations of parental alleles.

• the union of two haploid gametes at fertilization results in a diploid zygote, the first cell of a new individual.

Bpa and abnormal Meiosis

In 1998, researchers at Case Western university were studying meiosis in mouse oocytes when they saw an unexpected and dramatic increase in abnormal meiosis events (Figure 8.16). the improper sorting of chromosomes into gametes is one of the main causes of human genetic disorders, which we will discuss in Chapter 9.

the researchers discovered that the spike in abnormal meiosis events began immediately after the mouse facility started washing the animals’ plastic cages and water bottles in a new, alkaline detergent. the detergent had damaged the plastic, which as a result was leaching bisphenol A (BpA). BpA is a synthetic chemical that mimics estrogen, the main female sex hormone in animals. though it has been banned for use in baby bottles, BpA is still widely used to manufacture other plastic items and epoxies (such as the coating on the inside of metal cans of food). BpA-free plastics are often manufactured with a related compound, bisphenol S (BpS), that has effects similar to BpA.

1. What percentage of mouse oocytes displayed abnormalities of meiosis with no exposure to damaged caging?

2. Which group of mice had the most meiotic abnormalities? 3. What is abnormal about metaphase I as it is occurring in the

oocytes shown in Figure 8.16B, C, and D?

Digging Into Data Total number of oocytesCaging materials

Control: New cages with glass bottles 271 5 (1.8%)

Damaged bottles 197 53 (26.9%)

Damaged cages with damaged bottles 58 24 (41.4%)

Damaged cages with glass bottles Mild damage 401 35 (8.7%) Severe damage 149 30 (20.1%)

Abnormalities

B C D

Figure 8.16 Meiotic abnormalities associated with exposure to plastic. Fluorescence micrographs show nuclei of single mouse oocytes (female germ cells) in metaphase I. (a) normal metaphase; (B–D) examples of abnormal meta- phase. Chromosomes are stained red; spindle fibers, green. (A–D) Reprinted from Current Biology, Vol 13, (Apr 03), Authors Hunt, Koehler, Susiarjo, Hodges, Ilagan, Voight, Thomas, Thomas, and Hassold, Bisphenol A Exposure Causes Meiotic Aneuploidy in the Female Mouse, pp. 546–553, © 2003 Cell Press. Published by Elsevier Ltd. With permission from Elsevier.

addition, any number of genes may occur as different alleles on the maternal and paternal chromosomes, and crossing over makes mosaics of that genetic infor- mation. Then, out of all the male and female gametes that form, which two actually get together at fertilization is a matter of chance. Are you getting an idea of why such fascinating combinations of traits show up among the generations of your own family tree?

crossing over process in which homologous chro- mosomes exchange corresponding segments during meiosis.

gamete Mature, haploid reproductive cell; e.g., an egg or a sperm.

zygote Diploid cell that forms when two gametes fuse; the first cell of a new individual.

Meiosis halves the chromosome number, and fertilization restores it.

146

Summary Section 8.1 An immortal line of human cells (Hela) is a legacy of cancer victim Henrietta lacks. Researchers all over the world continue to work with these cells in their efforts to unravel the mechanisms of cancer.

Section 8.2 A cell cycle starts when a new cell forms, and ends when the cell reproduces. Most of a cell’s activities occur during interphase. A eukaryotic cell reproduces by dividing: nucleus first, then cytoplasm. Mitosis, a nuclear division mechanism that maintains

the chromosome number, is the basis of growth and tissue repair in multicelled species. Mitosis is also the basis of asexual reproduction in many species.

dNA replication occurs before mitosis begins, so each of the cell’s homologous chromosomes consists of two molecules of dNA (sister chromatids) attached at the centromere. Mitosis occurs in four stages. during prophase, the chromosomes condense, the nuclear envelope breaks up, and microtubules assemble into a spindle. spindle microtubules attach to the chromosomes at the centromere. At metaphase, all of the chromosomes are aligned in the middle of the cell. during anaphase, the spindle separates the sister chromatids of each chromosome and moves them toward opposite sides of the cell. during telophase, two new nuclei form, each with the parental chromosome number.

In most cases, nuclear division is followed by cytoplasmic division. In animal cells, a contractile ring pulls the plasma membrane inward, forming a cleavage furrow that pinches the cytoplasm in two. In plant cells, vesicles merge as a cell plate that expands

and fuses with the plasma membrane, thus becoming a cross-wall that partitions the cytoplasm.

Section 8.3 The products of checkpoint genes work together to control the cell cycle. These molecules monitor the integrity of the cell’s dNA, and can pause the cycle until breaks or other problems are fixed. when checkpoint mechanisms fail, a cell loses control

over its cell cycle, and its abnormally dividing descendants form a neoplasm. Neoplasms may form lumps called tumors.

Mutations can turn some genes into tumor-causing oncogenes. Mutations in multiple checkpoint genes can transform benign neoplasms into malignant ones. Cells of malignant neoplasms can break loose from their home tissues and colonize other parts of the body, a process called metastasis. Cancer occurs when cells of a malignant neoplasm physically and metabolically disrupt body tissues. Telomere length limits the number of times that a normal cell can divide, a fail-safe mechanism in case the cell loses control over its cell cycle.

Section 8.4 Sexual reproduction mixes up the genetic information of two parents. The offspring of sexual reproducers typically vary in shared, inherited traits. particularly in changing environments, this variation can offer an evolutionary advantage over genetically

identical offspring produced by asexual reproduction. sexual reproduction produces offspring whose body cells

contain pairs of chromosomes, one of each homologous pair from the mother and the other from the father. The two chromosomes of a homologous pair carry the same genes. paired genes on homologous chromosomes may vary in dNA sequence, in which case they are called alleles. Alleles are the basis of differences in shared traits. They arise by mutation.

Section 8.5 Meiosis, the basis of sexual reproduction in eukaryotes, is a nuclear division mechanism that halves the chromosome number. dNA replication occurs before meiosis begins, so each chromosome consists of two molecules of dNA (sister chromatids).

Two nuclear divisions occur during meiosis. In the first nuclear division (meiosis I), all of the homologous chromosomes line up and exchange corresponding segments. This crossing over mixes up the alleles on maternal and paternal chromosomes. The homologous chromosomes are then moved apart and packaged in separate nuclei. This stage reduces the chromosome number, from diploid (2n) to haploid (n). The second nuclear division (meiosis II) occurs in both haploid nuclei that formed in meiosis I. sister chromatids separate in this stage, so at the end of meiosis each chromosome consists of one molecule of dNA. Four haploid nuclei typically form. Meiosis is necessary for the production of haploid gametes. The fusion of two gametes at fertilization restores the diploid parental chromosome number in the zygote, the first cell of the new individual.

answers in appendix i

1. Mitosis and cytoplasmic division function in . a. asexual reproduction of single-celled eukaryotes b. growth and tissue repair in multicelled species c. asexual reproduction in prokaryotes d. both a and b

2. A duplicated chromosome has how many chromatids? a. one c. three b. two d. four

B b

A A

self-Quiz

HOW CeLLS RepRODuCe CHapter 8 147

1. when a cell reproduces by mitosis and cytoplasmic division, does its life end?

3. Make a sketch of meiosis in a cell with a diploid chromosome number of 4. Now try it when the chromosome number is 3.

4. The diploid chromosome number for the body cells of a frog is 26. what would that number be after three generations if meio- sis did not occur before gamete formation?

5. which nuclear division, meiosis I or meiosis II, is most similar to mitosis?

3. A cell with two of each type of chromosome has a chromosome number that is . a. diploid c. tetraploid b. haploid d. abnormal

4. Homologous chromosomes . a. originate with two parents b. are sister chromatids

5. Interphase is the part of the cell cycle when . a. a cell ceases to function b. the spindle forms prior to nuclear division c. dNA replication occurs d. mitosis proceeds

6. After mitosis, the chromosome number of a descendant cell is the parent cell’s. a. the same as c. rearranged compared to b. one-half of d. doubled compared to

7. one evolutionary advantage of sexual over asexual reproduction may be that it produces . a. more offspring per individual b. more variation among offspring c. healthier offspring

8. Alternative forms of the same gene are . a. gametes c. alleles b. homologous d. oncogenes

9. Meiosis is a necessary part of sexual reproduction because it . a. divides two nuclei into four new nuclei b. reduces the chromosome number for gametes c. produces clones that can cross over

10. Crossing over mixes up . a. chromosomes c. zygotes b. alleles d. gametes

11. sexual reproduction in animals requires . a. meiosis c. gametes b. fertilization d. all of the above

12. which of the following is one of the very important differences between mitosis and meiosis? a. Chromosomes align in the middle of the cell only in meiosis. b. Homologous chromosomes swap segments only in meiosis. c. sister chromatids separate only in meiosis.

13. The cell illustrated on the right is in anaphase I, not anaphase II. I know this because . a. crossing over has already occurred b. the chromosomes are still duplicated c. a spindle has formed. d. sister chromatids have separated

14. Match each stage with the events listed. prophase a. sister chromatids move apart metaphase b. chromosomes condense anaphase c. new nuclei form telophase d. dNA replication interphase e. all chromosomes are aligned in the middle of the cell

15. Match each term with the best description. cell plate a. lump of abnormal cells spindle b. forms at fertilization tumor c. divides plant cells contractile ring d. mash-up time gamete e. dangerous metastatic cells cancer f. made of microtubules zygote g. haploid prophase I h. makes an indentation

The eukaryotic cell in the photo on the left is in the process of cytoplasmic division. Is this cell from a plant or an animal? How do you know?

Critical Thinking

Visual Question

9.1 Menacing Mucus 150

9.2 Tracking Traits 151

9.3 Mendelian Inheritance Patterns 152

9.4 Beyond Simple Dominance 155

9.5 Complex Variation in Traits 158

9.6 Human Genetic Analysis 160

9.7 Human Genetic Disorders 161

9.8 Chromosome Number Changes 165

9.9 Genetic Screening 168

P at

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150 Unit 2 GeNeTICS

9.1 Menacing Mucus REMEMBER: Polypeptide chains twist, fold, and pack into functional domains; a protein’s function arises from and depends on its shape (Section 2.9). Vesicles move substances among organelles of the eR, and to and from the plasma membrane (3.5). Water moves across a membrane by osmosis, from a hypotonic to a hyper- tonic fluid (4.5). In active transport, a transport protein uses energy to pump a solute against its gradient across a cell membrane; in endocytosis, a small patch of plasma membrane balloons into cytoplasm and becomes a vesicle (4.6). During protein synthesis, amino acids are specified by three-nucleotide codons (7.4). A deletion is a mutation in which one or more nucleotides are lost from a chromosome (7.6).

In 1988, researchers discovered a gene that, when mutated, causes the most com- mon fatal genetic disorder in the United States: cystic fibrosis (CF). The gene they discovered, CFTR, encodes an active transport protein that moves chloride ions out of epithelial cells. Sheets of epithelial cells line the passageways and ducts of the lungs, liver, pancreas, intestines, and reproductive system. When the CFTR protein pumps chloride ions out of these cells, water follows the solute by osmosis. The two- step process maintains a thin, watery film on the surface of epithelial cell sheets. Mucus slides easily over the wet sheets of cells.

The mutation most commonly associated with cystic fibrosis is a deletion that removes a single codon from the CFTR gene. The protein product of the mutated gene is missing one amino acid, and as a result it misfolds in a tiny region. This small defect interferes with cellular processes that would otherwise finish the protein and install it in the plasma membrane. Normally, a newly translated CFTR polypeptide is modified by the endoplasmic reticulum (ER) and exported to a Golgi body, which attaches carbohydrates to it. The finished protein is then packaged in vesicles routed to the plasma membrane. CFTR polypeptides with the miss- ing amino acid are produced properly, but a cellular quality control mechanism recognizes the misfolded region and destroys most of them before they leave the ER. The few that make it to the plasma membrane are quickly taken back into the cell by endocytosis and destroyed.

Epithelial cell membranes that lack the CFTR protein cannot transport chloride ions. Too few chloride ions leave these cells. Not enough water leaves them either, so the surfaces of epithelial cell sheets are too dry. Mucus that normally slips and slides through the body’s tubes sticks to their walls instead. Thick globs of mucus accu- mulate and clog passageways and ducts throughout the body. Breathing becomes difficult as the mucus obstructs the smaller airways of the lungs. Digestive problems arise as ducts that lead to the gut become clogged with mucus. Males are typically infertile because their sperm flow is hampered.

In addition to its role in chloride ion transport, the CFTR protein also helps alert the immune system to the presence of disease-causing bacteria in the lungs. It functions as a receptor by binding directly to these bacteria and causing them to be taken into the cell by endocytosis. In epithelial cells lining the respiratory tract, endocytosis of bacteria triggers an immune response. Bacteria-fighting molecules that are produced in this response keep microbial populations at bay. When the cells lack CFTR, the early alert system fails, so bacteria have time to multiply before being detected by the immune system. Thus, chronic bacterial infections of the lungs are a hallmark of cystic fibrosis. Antibiotics help control infections, but there is no cure for the disorder. Most affected people die before age thirty, when their tormented lungs fail (Figure 9.1).

Brandon, 18Lindsay, 22

Jeff, 21Cody, 23

Savannah, 19Ben, 23

Figure 9.1 A few of the many victims of cystic fibrosis. At least one young person dies every day in the United States from complications of this disease, which occurs most often in people of northern european ancestry. Top row: left, courtesy of © The Cody Dieruf Benefit Foundation, www.breathinisbelievin.org; right, courtesy of © Bobby Brooks and The Family of Jeff Baird. Middle row: left, courtesy of The Family of Benjamin Hill, reprinted with permission of © Chappell/Marathonfoto; right, Courtesy of © The Family of Savannah Brooke Snider. Bottom row: left, courtesy of © Steve & Ellison Widener and Breathe Hope, http://breathehope.tamu.edu; right, courtesy of © The Family of Brandon Herriott.

Application

PATTeRNS of INHeRITANCe ChAptER 9 151

9.2 Tracking Traits REMEMBER: Inheritance is transmission of DNA to offspring (Section 1.3). DNA was proven to be hereditary material in the 1950s (6.2). Information encoded in a DNA sequence occurs in units called genes; a cell uses the information in a gene to make an RNA or protein product (7.2). Diploid body cells of sexual reproducers have two sets of chromosomes, one inherited from each of two parents; homologous chromo- somes carry the same genes, which can differ as alleles; alleles may encode different forms of the gene’s product; almost every shared trait varies a bit among individuals of a species, and alleles of shared genes are the basis of this variation (8.4). At fertil- ization, two gametes fuse to produce a zygote, the first cell of a new individual (8.5).

In the nineteenth century, people thought that hereditary material must be some type of fluid, with fluids from both parents blending at fertilization like milk into coffee. However, the idea of “blending inheritance” failed to explain what people could see with their own eyes. Children sometimes have traits such as freckles that do not appear in either parent. A cross between a black horse and a white one does not produce gray offspring. The naturalist Charles Darwin had no hypoth- esis to explain such phenomena, even though inheritance was central to his theory of natural selection (Chapter 11 returns to this theory). At the time, no one knew

that hereditary information is divided into discrete units (genes), an insight that is critical to understanding how traits are inherited. However, even before Darwin pre- sented his theory, someone had been gathering evidence that would support it. Gregor Mendel (left), an Austrian monk, had been carefully breeding thousands of pea plants. By keeping detailed records of how traits passed from one generation to the next, Mendel had been collect- ing evidence of how inheritance works.

Mendel’s Experiments Mendel cultivated the garden pea plant (Figure 9.2). This species is naturally self-fertilizing, which means its flowers produce male and female gametes

that form viable embryos when they meet up. To prevent an individual pea plant from self-fertilizing, Mendel removed the pollen-bearing parts (anthers) from its flowers. He then cross-fertilized the flowers by brushing their egg-bearing parts (carpels) with pollen from another plant

. He collected seeds 3

from the cross-fertilized individual, and recorded the traits of the new pea plants that grew from them

. Many of Mendel’s experiments, which are called crosses, started with plants that

“breed true” for particular traits such as white flowers or purple flowers. Breeding true for a trait means that, new mutations aside, all offspring have the same form of the trait as the parent(s), generation after generation. For example, all offspring of pea plants that breed true for white flowers also have white flowers. As you will see in the next section, Mendel discovered that crossing pea plants yields offspring with traits that often appear in predictable patterns. Mendel’s meticulous work tracking pea plant traits led him to conclude (correctly) that hereditary information passes from one generation to the next in distinct units.

Inheritance in Modern Terms Mendel discovered hereditary units, which we now call genes, almost a century before the discovery of DNA. Today, we know that individuals of a species share certain traits because their chromosomes carry the

anther

carpelcarpel

Figure 9.2 Breeding experiments with the garden pea. Top, Valentina Razumova/Shutterstock; (#1) Jean M. Labat/ardea.com.

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In the flowers of a garden pea plant (above), pollen grains that form in anthers (right) produce male gametes. female gam- etes form in carpels.

experimenters control the transfer of heredi- tary material from one pea plant to another by cutting off a flow- er’s pollen-producing anthers (to prevent it from self-fertilizing), then brushing pollen from another flower onto its egg- producing carpel.

In this example, pollen from a plant with pur- ple flowers is brushed onto the carpel of a white-flowered plant.

Later, seeds develop inside pods of the cross-fertilized plant. An embryo in each seed develops into a mature pea plant.

every plant that arises from the cross has purple flowers. Predictable patterns such as this are evidence of how inheritance works.

152 Unit 2 GeNeTICS

same genes, and that each gene occurs at a specific location on a particular chro- mosome (Figure 9.3). The diploid body cells of humans and other animals contain pairs of genes, on pairs of homologous chromosomes. In most cases, both genes of a pair are expressed. Genes at the same location on a pair of homologous chro- mosomes may be identical, or they may vary as alleles. Organisms breed true for a trait because they carry identical alleles of genes governing that trait. An individual with two identical alleles of a gene is homozygous for the allele (homo– means the same). By contrast, an individual with two different alleles of a gene is heterozy- gous (hetero–, mixed). A hybrid is a heterozygous individual produced by a cross or mating between individuals that breed true for different forms of a trait. Homo- zygous and heterozygous are examples of genotype, the particular set of alleles an individual carries. Genotype is the basis of phenotype, which refers to the individ- ual’s observable traits. “White-flowered” and “purple-flowered” are examples of pea plant phenotypes that arise from differences in genotype.

The phenotype of a heterozygous individual depends on how the products of its two different alleles interact. In many cases, the effect of one allele influences the effect of the other, and the outcome of this interaction is reflected in the individual’s phenotype. An allele is dominant when its effect masks that of a recessive allele paired with it. A dominant allele is often represented by an italic capital letter such as A; a recessive allele, with a lowercase italic letter such as a. Consider the purple- and white-flowered pea plants that Mendel studied. In these plants, the allele that specifies purple flowers (let’s call it P) is dominant over the allele that specifies white flowers (p). Thus, a pea plant homozygous for the dominant allele (PP) has purple flowers; one homozygous for the recessive allele (pp) has white flowers (Figure 9.4). A heterozygous plant (Pp) has purple flowers.

9.3 Mendelian Inheritance Patterns REMEMBER: During the nuclear division process of meiosis, homologous chro- mosomes cross over and then separate; crossing over makes new combinations of parental alleles for forthcoming gametes; at fertilization, two gametes fuse and produce a zygote, which is the first cell of a new individual (Section 8.5).

When homologous chromosomes separate during meiosis, the gene pairs on those chromosomes separate too. Each gamete that forms carries only one of the two genes of a pair. Let’s use our alleles for purple and white flowers in an example (Fig- ure 9.5). Plants homozygous for the dominant allele (PP) can only make gametes that carry allele P

. Plants homozygous for a recessive allele (pp) can only make gametes that carry allele p

. If these homozygous plants are crossed (PP 3 pp),

Figure 9.3 Locations of a few genes on two human chromosomes. Genetic disorders arising from mutations in the genes are shown in parentheses. The number or letter below a chromosome is its name; staining reveals characteristic banding patterns that are illustrated here. Appendix III has a similar map of all 23 human chromosomes.

Take-Home Message 9.2 how do alleles contribute to traits?

• Genotype (an individual’s set of alleles) is the basis of phenotype (the individual’s observable traits).

• A homozygous individual has two identical alleles of a gene. A heterozygous indi- vidual has two nonidentical alleles.

• A dominant allele masks the effect of a recessive allele in a heterozygous individual. Figure 9.4 Genotype gives rise to phenotype. In this example, the dominant allele P specifies purple flowers; the recessive allele p, white flowers. © Tamara Kulikova/Shutterstock.

genotype

PP (homozygous for dominant allele P)

pp (homozygous for recessive allele p)

Pp (heterozygous for alleles P and p)

phenotype

Figure it Out: Which individual is a hybrid?

Answer: The heterozygous one

TCR β subunit

cytochrome c

elastin

leptin (obesity) (blue-deficient colorblind)

DLX 5/6 homeotic genes

CFTR (cystic fibrosis)

7 15

ribosomal RNA

skin pigmentation

fibrillin 1 (Marfan syndrome)

(Tay–Sachs disease)TCR β subunit

cytochrome c

elastin

leptin (obesity) (blue-deficient colorblind)

DLX 5/6 homeotic genes

CFTR (cystic fibrosis)

7 15

ribosomal RNA

skin pigmentation

fibrillin 1 (Marfan syndrome)

(Tay–Sachs disease)

PATTeRNS of INHeRITANCe ChAptER 9 153

only one outcome is possible: A gamete carrying allele P meets up with a gamete carrying allele p

. All of the offspring of this cross will have both alleles—they will be heterozygous (Pp). Because all of the offspring will carry the dominant allele P, all will have purple flowers. A grid called a Punnett square is helpful for predicting the genetic and phenotypic outcomes of such crosses (Figure 9.6).

Our example illustrated a pattern so predictable that it can be used as evidence of a dominance relationship between alleles, as the following experiments illustrate.

Monohybrid Crosses Dominance relationships between alleles determine the phenotypic outcome of a monohybrid cross, in which individuals with the same two alleles of a gene are crossed (Pp 3 Pp, for example). The frequency at which traits associated with the alleles appear among the offspring depends on whether one of the alleles is dominant over the other.

To make a monohybrid cross, we would start with individuals that breed true for two different forms of a trait. In garden pea plants, flower color (purple and white) is one example of a trait with two distinct forms, but there are many others. A cross between individuals that breed true for different forms of the trait yields hybrid offspring, all with the same set of alleles governing the trait. A cross between two of these F1 (first generation) hybrids is the monohybrid cross. The frequency at which the two traits appear in the F2 (second generation) offspring offers informa- tion about a dominance relationship between the two alleles. (F is an abbreviation for filial, which means offspring.)

Figure 9.5 Segregation of genes on homologous chromosomes into gametes. Homologous chromosomes separate during meiosis, so the pairs of genes they carry separate too. each of the resulting gametes carries one of the two members of each gene pair.

All gametes made by a parent homozygous for a dominant allele carry that allele.

All gametes made by a parent homozygous for a recessive allele carry that allele.

If these two parents are crossed, the union of any of their gametes at fertilization produces a zygote with both alleles. All offspring of this cross will be heterozygous.

dominant Refers to an allele that masks the effect of a recessive allele on the homologous chromosome.

genotype The particular set of alleles that is carried in an individual’s chromosomes.

heterozygous Having two different alleles of a gene.

homozygous Having identical alleles of a gene.

monohybrid cross Cross between two individuals identically heterozygous for alleles of one gene; for example Aa 3 Aa.

phenotype An individual’s observable traits.

punnett square Diagram used to predict the genetic and phenotypic outcomes of a cross.

recessive Refers to an allele with an effect that is masked by a dominant allele on the homologous chromosome.

p p

meiosis I

DNA replication

meiosis II

gametes (P) gametes (p)

P P

PP PP

PPPP

zygote (Pp)

P p

pp pp

p p p p

1 2

female gametes m

al e

ga m

et es

p p

Pp Pp

p p

Pp Pp

p p

Figure 9.6 Making a punnett square. Parental gametes are listed in circles on the top and left sides of a grid. each square is filled with the combination of alleles that would result if the gametes in the corresponding row and column met up.

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P p

parent plant homozygous

for purple flowers

parent plant homozygous

for white flowers

two types of gametes

Pp hybrid

A All of the F1 offspring of a cross between two plants that breed true for different forms of a trait are identically heterozygous (Pp). These offspring make two types of gametes: P and p.

B A monohybrid cross is a cross between these F1 offspring. In this example, the phenotype ratio in F2 offspring is 3:1 (3 purple to 1 white).

PP Pp

Pp pp

A cross between two purple-flowered heterozygous plants (Pp) offers an example of a monohybrid cross. Each individual can make two types of gametes: ones that carry a P allele, and ones that carry a p allele (Figure 9.7A). So, in a mono- hybrid cross between Pp plants (Pp 3 Pp), the two types of gametes can meet up in four possible ways at fertilization:

Three of four possible outcomes of this cross include at least one copy of the domi- nant allele P. In other words, each time fertilization occurs, there are 3 chances in 4 that the resulting zygote will have a P allele (and the individual will make purple flowers). There is 1 chance in 4 that the zygote will have two p alleles (and the individual will make white flowers). Thus, the probability that a particular offspring of this cross will have purple or white flowers is 3 purple to 1 white—a ratio of 3:1 (Figure 9.7B). The 3:1 pattern is evidence that purple and white flower color are specified by alleles with a clear dominance relationship: Purple is dominant; white, recessive. If the probability of an individual inheriting a particular genotype is difficult to imagine, think about it in terms of many offspring: In this example, there will be roughly three purple-flowered plants for every white-flowered one.

Dihybrid Crosses A monohybrid cross allows us to study a dominance relation- ship between alleles of one gene. What about alleles of two genes? An individual heterozygous for alleles of two genes (AaBb, for example) is called a dihybrid, and a cross between two such individuals is a dihybrid cross. As with a monohybrid cross, the frequency of traits appearing among the offspring of a dihybrid cross depends on the dominance relationships between the alleles.

To make a dihybrid cross, we would start with individuals that breed true for two different traits. Let’s use a gene for flower color (P, purple; p, white) and one for plant height (T, tall; t, short) in an example. Figure 9.8 shows a dihybrid cross starting with one parent plant that breeds true for purple flowers and tall stems (PPTT ), and one that breeds true for white flowers and short stems ( pptt). The PPTT plant only makes gametes with the dominant alleles (PT); the pptt plant only makes gametes with the recessive alleles (pt)

. So, all offspring from a cross between these two plants (PPTT 3 pptt) will be dihybrids (PpTt) with purple flow- ers and tall stems

. Four combinations of P and T alleles are possible in the gametes of PpTt

dihybrids 3

. If two of these plants are crossed (a dihybrid cross, PpTt 3 PpTt), the four types of gametes can combine in sixteen possible ways at fertilization

. Nine of the sixteen genotypes would give rise to tall plants with purple flowers; three, to short plants with purple flowers; three, to tall plants with white flowers; and one, to short plants with white flowers. Thus, the ratio of phenotypes among the offspring of this dihybrid cross would be 9:3:3:1.

How two gene pairs get sorted into gametes depends partly on whether the two genes are on the same chromosome. When homologous chromosomes sepa- rate during meiosis, either member of the pair can end up in either of the two new nuclei that form. Thus, genes on one chromosome pair assort into gametes independently of genes on the other chromosome pairs. What about genes on the

codominance Inheritance pattern in which the full and separate phenotypic effects of two alleles are apparent in heterozygous individuals.

dihybrid cross Cross between two individuals identically heterozygous for alleles of two genes; for example AaBb 3 AaBb.

incomplete dominance Inheritance pattern in which one allele is not fully dominant over another, so the heterozygous phenotype is an intermediate blend between the two homozygous phenotypes.

Figure 9.7 Example of a monohybrid cross.

possible Event Offspring Genotype Resulting phenotype

Sperm P meets egg P zygote genotype is PP individual has purple flowers Sperm P meets egg p zygote genotype is Pp individual has purple flowers Sperm p meets egg P zygote genotype is Pp individual has purple flowers Sperm p meets egg p zygote genotype is pp individual has white flowers

A. All of the f1 (first generation) offspring of a cross between two plants that breed true for different forms of a trait are identically heterozygous (Pp). These offspring make two types of gametes: P and p.

B. A monohybrid cross is a cross between the f1 offspring. In this example, the phenotype ratio among the f2 (second generation) offspring is 3:1 (three purple to one white).

P p

parent plant homozygous

for purple flowers

parent plant homozygous

for white flowers

two types of gametes

Pp hybrid

A All of the F1 offspring of a cross between two plants that breed true for different forms of a trait are identically heterozygous (Pp). These offspring make two types of gametes: P and p.

B A monohybrid cross is a cross between these F1 offspring. In this example, the phenotype ratio in F2 offspring is 3:1 (3 purple to 1 white).

PP Pp

Pp pp

Figure it Out: In this example, how many possible genotypes are there in the f2 generation? Answer: Three (PP, Pp, and pp)

PATTeRNS of INHeRITANCe ChAptER 9 155

same chromosome? Pea plants have seven chromosomes. Mendel studied seven pea genes, and all of them assorted into gametes independently of one another. Was he lucky enough to choose one gene on each of those chromo- somes? As it turns out, some of the genes Mendel studied are on the same chromosome. These genes are far enough apart that crossing over occurs between them very frequently—so frequently that they tend to assort into gametes independently, just as if they were on different chromosomes. By contrast, genes that are very close together on a chromosome usually do not assort independently into gametes, because crossing over does not happen between them very often. Thus, gametes usually end up with parental combi- nations of alleles of these genes.

9.4 Beyond Simple Dominance REMEMBER: Sickle-cell anemia is the outcome of a base-pair substitution in the beta globin gene (Section 7.6).

In the Mendelian inheritance patterns discussed in the previous section, the effect of a dominant allele on a trait fully masks that of a recessive one. Other inheritance patterns are more common, and more complex.

Incomplete Dominance In an inheritance pattern called incomplete dominance, one allele is not fully dominant over the other, so the heterozy- gous phenotype is an intermediate blend of the two homozygous phenotypes. A gene that affects flower color in snapdragon plants is an example. One allele of the gene (R) encodes an enzyme that makes a red pigment. The enzyme encoded by an allele with a mutation (r) cannot make any pigment. Plants homozygous for the R allele (RR) make a lot of red pigment, so they have red flowers. Plants homozygous for the r allele (rr) make no pigment, so their flowers are white. Heterozygous plants (Rr) make only enough pigment to tint their flowers pink. A cross between two pink-flowered heterozygous plants yields red-, pink-, and white-flowered offspring in a 1:2:1 ratio.

Codominance In an inheritance pattern called codominance, both alleles are fully expressed in heterozygous individuals; neither allele is dominant or recessive. Alleles of the ABO gene offer an example. This gene encodes an enzyme that modifies a carbohydrate on the surface of human red blood cells.

PtPT pT pt

parent plant homozygous

for purple flowers and long stems

PPTT pptt

parent plant homozygous

for white flowers and short stems

four types of gametes

PpTt dihybrid

PPTT PPTt

PPTt PPtt

PpTT PpTt

PpTt Pptt

PpTT PpTt

PpTt Pptt

ppTT ppTt

ppTt pptt

PT Pt pT pt

Take-Home Message 9.3 how are alleles distributed into gametes?

• Diploid cells have pairs of genes, on pairs of homologous chromosomes. The two genes of a pair (which may be identical or not) are separated from each other during meiosis, so they end up in different gametes.

• In most cases, the two genes of a pair are distributed into gametes indepen- dently of other gene pairs on other chromosomes.

• Gene pairs that are far apart on the same chromosome also tend to be distrib- uted independently into gametes.

In each individual homozygous for alleles of two genes, meiosis results in only one type of gamete.

A cross between the two homozygous individuals yields offspring heterozy- gous for alleles of two genes (dihybrids).

Meiosis in dihybrid individuals results in four kinds of gametes.

If two of the dihybrid individuals are crossed, the four types of gametes can meet up in 16 possible ways. of 16 possible offspring genotypes, 9 will result in plants that are purple- flowered and tall; 3, purple-flowered and short; 3, white- flowered and tall; and 1, white-flowered and short. Thus, the ratio of phenotypes is 9:3:3:1.

Figure 9.8 An example of a dihybrid cross. P and p are dominant and recessive alleles for flower color; T and t are dominant and recessive alleles for plant height.

156

Two alleles, A and B, encode slightly different versions of this enzyme, which in turn modify the carbohydrate differently. A third allele, O, has a mutation that prevents the enzyme product from becoming active, so the carbohydrate remains unmodified.

The alleles of the ABO gene that you carry determine the form of the carbohy- drate on your blood cells, so they are the basis of your ABO blood type (Figure 9.9). The A and the B allele are codominant when paired. If your genotype is AB, then you have both versions of the enzyme, and your blood type is AB. The O allele is recessive when paired with either the A or B allele. If your genotype is AA or AO, your blood type is A. If your genotype is BB or BO, it is type B. If you are OO, it is type O.

The immune system attacks any cell bearing molecules that do not occur in one’s own body, so receiving incompatible blood in a transfusion can be dangerous. An immune attack causes red blood cells to clump or burst, with potentially fatal results. Almost everyone makes the red blood cell carbohydrate (which is later modified in people with an A or B allele), so type O blood does not usually trigger an immune response in transfusion recipients. People with type O blood are called universal donors because they can donate blood to anyone. However, because their body is unfamiliar with the modified form of the carbohydrate made by people with type A or B blood, they can receive type O blood only. People with type AB blood can receive a transfusion of any ABO blood type, so they are called universal recipients.

Pleiotropy and Epistasis In an inheritance pattern called pleiotropy, a single gene influences multiple traits. Mutations that affect the gene’s product or its expres- sion affect all of the traits. Many complex genetic disorders, including sickle-cell anemia and cystic fibrosis, are caused by mutations in single genes. Marfan syn- drome, another example, is a result of mutations that affect fibrillin. Long fibers of this protein are part of elastic tissues that make up the heart, skin, blood vessels, tendons, and other body parts. Mutations can cause tissues to form with defective fibrillin or none at all. The largest blood vessel leading from the heart, the aorta, is particularly affected. Without a proper scaffold of fibrillin, the aorta’s thick wall is not as elastic as it should be, and it eventually stretches and becomes leaky. Thinned and weakened, the aorta can rupture during exercise—an abruptly fatal outcome. About 1 in 5,000 people have Marfan syndrome, and there is no cure. Its effects— and risks—are manageable with early diagnosis, but symptoms are easily missed. Affected people are tall and loose-jointed, but there are plenty of tall, loose-jointed people who do not have the syndrome. Thus, people with Marfan syndrome may die suddenly and early without ever knowing they had the disorder.

In a common inheritance pattern called polygenic inheritance or epistasis, one trait is affected by multiple gene products. Consider how fur color in dogs and other animals arises from pigments called melanins. A dark brown form of melanin gives rise to brown or black fur; a reddish melanin, to yellow fur. The products of several genes interact to carry out melanin synthesis and deposition in fur. In Labrador retriever dogs, alleles of two of these genes determine whether the individual has black, brown, or yellow fur (Figure 9.10).

Human skin color offers another example of epistasis. At least 100 gene prod- ucts affect this trait, which begins with melanosomes (organelles that make mela- nins). Most people have about the same number of melanosomes in their skin cells. Variations in skin color arise from differences in the size, shape, and cellular distri- bution of melanosomes in the skin, as well as in the kinds and amounts of melanins they make. These variations have a genetic basis. Consider one gene that encodes a transport protein in melanosome membranes. Nearly all people of African, Native American, or east Asian descent carry the same allele of this gene. A mutation that

Figure 9.9 Combinations of alleles that are the basis of blood type. Photo, Annie Cavanagh/Wellcome Images.

Figure 9.10 An example of epistasis. Interactions among products of two gene pairs affect fur color in Labrador retrievers. Dogs with alleles E and B have black fur. Those with an E and two recessive b alleles have brown fur. Dogs homozygous for the reces- sive e allele have yellow fur. Top, Susan Schmitz/Shutterstock.

Genotype:

phenotype:

or or AA

BO AB OO

A BAB O

epistasis Polygenic inheritance, in which a trait is influenced by multiple genes.

pleiotropy Inheritance pattern in which a single gene affects multiple traits.

Eb ebEB eB

EEBb

EEbb

EeBb

Eebb

EeBb

Eebb

eeBb

eebb

EEBB

EEBb

EeBB

EeBb

EeBB

EeBb

eeBB

eeBb

PATTeRNS of INHeRITANCe ChAptER 9 157

the Cystic Fibrosis Mutation and typhoid Fever

The Cf allele that causes most cases of cystic fibrosis is at least 50,000 years old and very common: 1 in 25 people carry it in some populations. Why is this allele so common if it is so dangerous? Consider that the Cf allele is eventually lethal in homo- zygous individuals, but not in those who are heterozygous. This allele is codominant with the normal allele. Heterozygous individuals typically have no symptoms of cystic fibrosis because their cells make enough of the normal CfTR protein to have normal chloride ion transport.

Researchers think the Cf allele has persisted because it offers heterozygous indi- viduals an advantage in surviving certain deadly infectious diseases. The unmutated CfTR protein triggers endocytosis when it binds to bacteria. This process is an essen- tial part of the body’s immune response to bacteria in the respiratory tract. However, the same function of CfTR allows bacteria to enter cells of the gastrointestinal tract, where they can be deadly. for example, internalization of Salmonella typhi bacteria by epithelial cells in the gut causes a common worldwide disease called typhoid fever. Symptoms include extreme fever and diarrhea, and the resulting dehydration causes delirium that may last several weeks. If untreated, it kills up to 30 percent of those infected. Around 600,000 people, most of whom are children, die from the disease each year.

In 1998, Gerald Pier and his colleagues compared the uptake of S. typhi by different types of epithelial cells: those heterozygous for the Cf allele, and those homozygous for the normal allele. (Cells homozygous for the Cf allele do not take up any S. typhi bacteria.) Some of the results are shown in figure 9.11.

Figure 9.11 Effect of the CF mutation on uptake of three strains of Salmonella typhi bacteria by epithelial cells.

Digging Into Data

occurred between 6,000 and 12,000 years ago gave rise to a different allele. This mutation, a single base-pair substitution, changed the 111th amino acid of the trans- port protein from alanine to threonine. The change results in less melanin—and lighter skin color—than the original African allele does. Today, nearly all people of European descent are homozygous for the mutated allele.

A person of mixed ethnicity may make gametes that contain different combina- tions of alleles for dark and light skin. It is fairly rare that one of those gametes con- tains all of the alleles for dark skin, or all of the alleles for light skin, but it happens (Figure 9.12). Skin color is only one of many human traits that vary as a result of single nucleotide mutations. The small scale of such changes offers a reminder that all of us share the genetic legacy of common ancestry.

1. Regarding the Ty2 strain of S. typhi, about how many more bacteria were able to enter normal cells (those expressing unmutated CFTR) than cells expressing the gene with the Cf mutation?

2. Which strain of bacteria entered normal epithelial cells most easily?

3. entry of all three S. typhi strains into the heterozygous epithelial cells was inhibited. Is it possible to tell from this graph which strain was most inhibited?

Take-Home Message 9.4 Do all traits appear in a Mendelian inheritance pattern?

• Some alleles are not dominant or recessive when paired. The heterozygous phenotype may include both homozygous phenotypes (codominance), or it may be a blend of the two homozygous phenotypes (incomplete dominance).

• In some cases, one gene influences multiple traits. In other cases, multiple genes influence the same trait.

Figure 9.12 Variation in human skin color begins with differences in alleles. Twins Kian and Remee are shown with their parents. Both of the children’s grandmothers are of european descent, and have pale skin. Both of their grandfathers are of African descent, and have dark skin. The twins inherited different alleles of some genes that affect skin color from their parents, who, given the appearance of their children, must be heterozygous for those alleles. © Gary Roberts/worldwidefeatures.com.

N um

be r o

f b ac

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ed b

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lls

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106

105

Strain of Salmonella typhi

Cells heterozygous for the Cf allele

Normal cells

167 7251Ty2

158 Unit 2 GeNeTICS

9.5 Complex Variation in Traits REMEMBER: Mutations are uncommon in a normal cell (Section 7.6). expression of a homeotic gene directs formation of a specific body part; environmentally triggered changes in DNA methylation can be permanent and heritable (7.7). Growth factors stimulate cell division and differentiation (8.3). Genetic diversity offers sexual repro- ducers an advantage in a changing environment (8.4).

The pea plant phenotypes that Mendel studied appeared in two or three forms, which made them easy to track through generations. However, many other traits do not appear in distinct forms. Such traits are often the result of complex genetic interac- tions—multiple genes, multiple alleles, or both—with added environmental influ- ences. Tracking traits with complex variation presents a special challenge, which is why the genetic basis of many of them has not yet been completely unraveled.

The phrase “nature versus nurture” refers to a centuries-old debate about whether human behavioral traits arise from one’s genetics (nature) or from envi- ronmental factors (nurture). We now know that both play a substantial role. The environment affects the expression of many genes, which in turn affects phenotype— including behavioral traits. We can summarize this thinking with an equation:

environmentgenotype phenotype

Epigenetics research is revealing that the environment has an even greater contribu- tion to this equation than most biologists had suspected. Environmental cues trigger internal pathways that methylate particular regions of DNA, so they suppress gene expression in those regions. In humans and other animals, DNA methylation pat- terns can be permanently and heritably affected by diet, stress, and exercise, and also by exposure to drugs and toxins such as tobacco, alcohol, arsenic, and asbestos.

Mechanisms that adjust phenotype in response to external cues are part of an individual’s normal ability to adapt to environmental change. Consider the water flea, a tiny aquatic animal that lives in standing pools of fresh water such as seasonal ponds and ditches. In these pools, water conditions such as temperature, oxygen content, and salinity vary dramatically over time and between different parts of the pool. Water fleas have a lot of genes—many more than humans and other animals. Environmental cues trigger adjustments in gene expression that change a flea’s form and function to suit its current environment. For example, a water flea that swims to the bottom of a pond can survive the low oxygen conditions there by turning on expression of seven genes involved in the production of hemoglobin—and turning red (Figure 9.13A). The newly produced hemoglobin improves the individual’s abil- ity to absorb oxygen from the water. In the presence of insect predators, a water flea makes a protective pointy helmet, a long tail spine, and teeth on its neck. Water fleas can also switch between asexual and sexual modes of reproduction. During early spring, food and space are typically abundant, and competition for these resources is scarce. Under these conditions, water fleas reproduce rapidly by asexual means, giving birth to large numbers of female offspring that quickly fill the pool. Later in the season, competition intensifies as the pool’s water becomes warmer, saltier, and more crowded. Then, some of the water fleas start giving birth to males, and the population begins to reproduce sexually. The increased genetic diversity of sexually produced offspring may offer an advantage in the more challenging environment.

In many mammals, seasonal changes in temperature and the length of day affect the production of melanin and other pigments that color skin and fur. These

Figure 9.13 Some environmental effects on phenotype. (A) From Science 4 February 2011: Vol 331 no. 6017 pp. 555–561, Reprinted with permission from AAAS; (B) left, Jupiter Images Corporation; right, © age fotostock/SuperStock; (C) photo, Igor Sokolov (breeze)/Shutterstock.com.

A. Under low-oxygen conditions, a water flea switches on genes involved in producing hemoglobin. Producing this red protein enhances the individual’s ability to take up oxygen from water. The flea on the left has been living in water with a normal oxygen content; the one on the right, in water with a low oxygen content.

B. The color of the snowshoe hare’s fur varies by season. In summer, the fur is brown (left); in winter, white (right). Both forms offer seasonally appropriate camouflage from predators.

C. The height of a mature yarrow plant depends on the elevation at which it grows.

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(c m

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PATTeRNS of INHeRITANCe ChAptER 9 159

species have different color phases in different seasons (Figure 9.13B). Hormonal signals triggered by the seasonal changes cause fur to be shed, and new fur grows back with different types and amounts of pigments deposited in it. The resulting change in phenotype provides these animals with seasonally appropriate camouflage from predators.

In plants, a flexible phenotype gives immobile individuals an ability to thrive in diverse habitats. For example, genetically identical yarrow plants grow to differ- ent heights at different altitudes (Figure 9.13C). More challenging temperature, soil, and water conditions are typically encountered at higher altitudes. Differences in altitude are also correlated with changes in the reproductive mode of yarrow: Plants at higher altitude tend to reproduce asexually, and those at lower altitude tend to reproduce sexually.

Researchers recently discovered several mutations associated with five human psychiatric disorders: autism, depression, schizophrenia, bipolar disorder, and atten- tion deficit hyperactivity disorder (ADHD). However, there must be environmental components to these disorders too, because the majority of people who carry these mutations never end up with a psychiatric disorder. Moreover, one person with the mutations might get one type of disorder, while a relative with the same mutations might get another: two different results from the same genetic underpinnings.

Animal models are helping us unravel some of the mechanisms by which environment can influence mental state. For example, we have discovered that learning and memory are associated with dynamic and rapid DNA modifications in animal brain cells. Mood is, too. Stress-induced depression causes methylation- based silencing of a particular nerve growth factor gene; some antidepressants work by reversing this methylation. As another example, rats whose mothers are not very nurturing end up anxious and having a reduced resilience for stress as adults. The difference between these rats and ones who had nurturing maternal care is traceable to epigenetic DNA modifications that result in a lower than normal level of another nerve growth factor. Drugs can reverse these modifications—and their effects. We do not yet know all of the genes that influence human mental state, but the implica- tion of such research is that future treatments for many psychiatric disorders will involve deliberate modification of methylation patterns in an individual’s DNA.

Continuous Variation Some traits occur in a range of small differences that is called continuous variation. Continuous variation can be an outcome of epistasis, in which multiple genes affect a single trait. The more genes and environmental fac- tors that influence a trait, the more continuous is its variation. Traits that arise from genes with a lot of alleles may also vary continuously. Some genes have regions of DNA in which a series of 2 to 6 nucleotides is repeated many times in a row. These short tandem repeats can spontaneously expand or contract very quickly com- pared with the typical rate of mutation, and the resulting changes in the gene’s DNA sequence may be preserved as alleles. For example, in dogs, short tandem repeats have given rise to 12 alleles of a homeotic gene that influences the length of the face, with longer repeats associated with longer faces (Figure 9.14A).

Human skin color varies continuously, as does human eye color (Figure 9.14B). The colored part of the eye is a doughnut-shaped structure called the iris. Iris color, like skin color, is the result of interactions among gene products that make and dis- tribute melanins. The more melanin deposited in the iris, the less light is reflected from it. Dark irises have dense melanin deposits that absorb almost all light, and reflect almost none. Green and blue eyes have the least amount of melanin, so they reflect the most light.

continuous variation A range of small differences in a shared trait.

short tandem repeat In chromosomal DNA, a sequence of a few nucleotides repeated multiple times in a row.

Figure 9.14 Examples of continuous variation. (A) WilleeCole/Shutterstock.com; (B) from left: first row, © szefel/Shutterstock.com; © Aaron Amat/Shutterstock.com; © Villedieu Christophe/Shutterstock.com; David Goodin; second row, jayfish/Shutterstock.com; © J. Helgason/Shutterstock.com; © Tischenko Irina/ Shutterstock.com; © Tatiana Makotra/Shutterstock; third row, © Vaaka/Shutterstock.com; © evantravels/Shutterstock.com; © rawcaptured/Shutterstock.com; Anemone/Shutterstock .com; fourth row, © Andrey Armyagov/Shutterstock; © Tatiana Makatra/Shutterstock.com; © lightpoet/Shutterstock.com; © Anemone/Shutterstock.com.

A. face length is a trait that varies continuously in dogs. A gene with 12 alleles influences this trait; all arose by the spontaneous insertion of short tandem repeats. The longer the alleles, the longer the face.

B. Iris color is a trait that varies continuously in humans.

The environment affects the expression of many genes, which in turn affects phenotype.

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How do we know if a particular trait varies continuously? Let’s use another human trait, height, in an example. First, the total range of phenotypes is divided into measurable categories—inches, in this case (Figure 9.15A). The individuals in each category are counted; these counts reveal the relative frequencies of phenotypes across the range of values. Finally, this data is plotted as a bar chart (Figure 9.15B). A graph line around the top of the bars shows the distribution of values for the trait. If the line is a bell-shaped curve, or bell curve, then the trait varies continuously.

9.6 Human Genetic Analysis REMEMBER: Sampling error is a difference between results obtained from a subset, and results from the whole (Section 1.6). environmentally driven epigenetic modifi- cations of DNA—and the resulting gene expression patterns—can be inherited (7.7).

Some organisms, including pea plants and fruit flies, are ideal for genetic studies. They have relatively few chromosomes, they reproduce quickly under controlled conditions, and breeding them in controlled settings poses few ethical problems. It does not take long to follow a trait through many generations. Humans, however, are a different story. We live under variable conditions, in different places, and we live as long as the geneticists who study our inheritance patterns. Most of us select our own mates and reproduce if and when we want to. Our families tend to be on the small side, so sampling error is a major factor in studying them. Because of these and other challenges, geneticists often use historical records to track traits through many generations of a family. They make and study pedigrees, standardized charts that illustrate the phenotypes of family members and genetic connections among them (Figure 9.16). Analysis of a pedigree can reveal whether a trait is associated with a dominant or recessive allele, and whether the allele is on an autosome or a sex chromosome. Pedigree analysis also allows geneticists to determine the prob- ability that a trait will reappear in future generations of a family or a population.

Types of Genetic Variation Few easily observed human traits follow Mendelian inheritance patterns. Like the flower color of Mendel’s pea plants, these traits arise from a single gene with alleles that have a clear dominance relationship. Consider the gene called MC1R. In humans, dogs, and other animals, MC1R encodes a protein that triggers production of the brownish melanin. Mutations can result in a defective protein; an allele with one of these mutations is recessive when paired with an unmutated allele. A person who is homozygous for a mutated allele does not make the brownish melanin—only the reddish type—so this individual has red hair. Most other human traits are polygenic, and many have epigenetic contributions that can originate in parents or even grandparents. Environmental effects make these traits even harder to study.

bell curve Bell-shaped curve; typically results from graphing frequency versus distribution for a trait that varies continuously.

pedigree Chart of family connections that shows the appearance of a trait through generations.

Take-Home Message 9.5 Do all traits occur in distinct forms?

• Many traits do not occur in distinct forms. The more genes and other factors that influence a trait, the more continuous is its range of variation.

• The environment influences gene expression, and therefore can alter phenotype.

B. Graphing the data that resulted from the experiment in A produces a bell-shaped curve, which is evidence that height does vary continuously in humans.

Figure 9.15 how to determine whether a particular trait varies continuously. (A) Courtesy of Ray Carson, University of Florida News and Public Affairs.

A. To see if human height varies continuously, male biol- ogy students at the University of florida were divided into categories of one-inch increments in height and counted.

Number of individuals

Measured values

63 64 65 66 67 68 69 70 71 72 73 74 75 76 77

PATTeRNS of INHeRITANCe ChAptER 9 161

III

5,5 6,6

6,6 5,5

5,5 6,6

* Gene not expressed in this carrier.

5,5 6,6

5,6 6,7

6,6 6,6

male marriage/mating

offspring individual showing trait being studied

sex not specified

I, II, III, IV...

generation

female Most of what we know about human genetics comes from research on

inherited abnormalities and disorders, because this information helps us develop treatments for affected people. A genetic abnormality is a rare or uncommon version of a trait, such as having six fingers on a hand or a web between two toes. Such abnormalities are not inherently life-threatening, and how you view them is a matter of opinion. By contrast, a genetic disor- der sooner or later causes medical problems that may be severe. A genetic disorder is often characterized by a specific set of symptoms (a syndrome). The next section discusses a few genetic disorders and abnormalities that are caused by mutations in single genes. Alleles that give rise to severe genetic disorders are generally rare in populations because they compromise the health and reproductive ability of their bearers. Why do they persist? Muta- tions periodically reintroduce them. In some cases, a codominant allele offers a survival advantage in a particular environment. You already learned about one example, the CF allele that causes cystic fibrosis. You will see additional examples in later chapters. Keep in mind that single-gene disor- ders are the least common kind. Far more people are affected by disorders that arise from a complex interplay of multiple genes and environmental fac- tors. Diabetes, asthma, obesity, cancer, heart disease, and multiple sclerosi s are like this. Despite intense research, our understanding of these disorders remains incomplete.

9.7 Human Genetic Disorders REMEMBER: Thousands of tiny pores span the nuclear envelope; intermedi- ate filaments of lamins support the nuclear envelope, and also help regulate processes inside the nucleus such as DNA replication; basement membrane supports and organizes animal tissues (Section 3.5). Autosomes are the same in both females and males; sex chromosomes differ between the sexes (6.3). An insertion is a mutation in which nucleotides are added to DNA; anemia is a deficiency in red blood cells or hemoglobin (7.6). one of the two X chromosomes in each cell of a female is an inactivated Barr body (7.7). Growth factors stimulate cell division (8.3).

Human genetic disorders inherited in a Mendelian pattern are typically cat- egorized by the chromosome of origin (autosome or sex chromosome) and whether alleles associated with them are dominant or recessive.

Figure 9.16 pedigrees. (B) Courtesy of Irving Buchbinder, DPM, DABPS, Community Health Services, Hartford CT; (C) Acey Harper/ Time & Life Pictures/Getty Images.

A. Standard symbols used in pedigrees.

C. for more than 30 years, researcher Nancy Wexler has studied the genetic basis of Huntington’s disease, an inherited disorder that causes progressive degeneration of the nervous system. Wexler and her team constructed an extended family tree for nearly 10,000 Venezuelans. Their pedigree analysis of relation- ships among unaffected and affected individuals revealed that a dominant allele on human chromosome 4 is the culprit. Wexler has a personal interest in the disorder: It runs in her family.

B. Above, a pedigree for poly- dactyly, a genetic abnormality in which a person has extra fingers (right), toes, or both. The number of fingers on each hand is indicated in black; toes on each foot, in red. Polydactyly that appears on its own is typically inherited in an autosomal domi- nant pattern. When part of a syn- drome (such as ellis–van Creveld syndrome), it can be inherited in an autosomal recessive pattern.

III

5,5 6,6

6,6 5,5

5,5 6,6

* Gene not expressed in this carrier.

5,5 6,6

5,6 6,7

6,6 6,6

male marriage/mating

offspring individual showing trait being studied

sex not specified

I, II, III, IV...

generation

female

Take-Home Message 9.6 how do we study inheritance patterns in humans?

• Human inheritance patterns are often studied by tracking genetic abnormali- ties or disorders through family trees.

• A genetic disorder is an inherited condition that causes medical problems. • A genetic abnormality is a rare but harmless version of an inherited trait. • only a few genetic disorders are governed by single genes and inherited in a

Mendelian pattern. Most human traits are polygenic, and many have epigen- etic contributions.

162 Unit 2 GeNeTICS

The Autosomal Dominant Pattern A trait associated with a dominant allele on an autosome appears in people who are heterozygous for it as well as those who are homozygous. Table 9.1 lists a few examples. Such traits appear in every generation of a family, and they occur with equal frequency in both sexes. When one parent is heterozygous, and the other is homozygous for the recessive allele, each of their children has a 50 percent chance of inheriting the dominant allele and having the associated trait (Figure 9.17A).

A form of hereditary dwarfism called achondroplasia offers an example of an autosomal dominant disorder (one caused by a dominant allele on an autosome). Mutations associated with achondroplasia occur in a gene for a growth factor recep- tor. The mutations cause the receptor, which normally slows bone development, to be overly active. About 1 in 10,000 people is heterozygous for one of these muta- tions. As adults, affected people are, on average, about 4 feet 4 inches (1.3 meters) tall, with arms and legs that are short relative to torso size (Figure 9.17B). An allele that causes achondroplasia can be passed to children because its expression does not interfere with reproduction, at least in heterozygous people. The homozygous condition results in severe skeletal malformations that cause early death.

Huntington’s disease is also inherited in an autosomal dominant pattern. Muta- tions that cause this disorder alter a gene for a cytoplasmic protein whose function is still unknown. The mutations are insertions that occur when a three-nucleotide short tandem repeat expands spontaneously. The oversized protein product of the altered gene gets chopped into pieces inside nerve cells of the brain. The pieces accumulate in cytoplasm as large clumps that eventually prevent the cells from functioning properly. Brain cells involved in movement, thinking, and emotion are particularly affected. Dramatic, involuntary jerking and writhing movements that are symptoms of the most common form of Huntington’s appear after age thirty. Affected people die during their forties or fifties. With this and other late-onset dis- orders, people may reproduce before symptoms appear, so the allele can be passed unknowingly to children.

Figure 9.17 Autosomal dominant inheritance. (B) © Newcastle Photos and Ivy & Violet Broadhead and family; (C) Photo courtesy of The Progeria Research Foundation and John Hurley.

A a

meiosis and gamete

formation

normal mother

affected father

3aa Aa

affected child

normal child

disorder-causing allele (dominant)

A. A dominant allele on an autosome (red ) is fully expressed in heterozygous people.

B. Achondroplasia affects Ivy Broadhead (left ), her brother, father, and grandfather.

C. Symptoms of Hutchinson–Gilford progeria are already evident in Megan Nighbor at age 5.

table 9.1 Some Autosomal Dominant traits in humans

Disorder/Abnormality Main Symptoms

Achondroplasia one form of dwarfism

Aniridia Defects of the eyes

Camptodactyly Rigid, bent fingers

familial hypercholesterolemia

High cholesterol, clogged arteries

Huntington’s disease Degeneration of the nervous system

Marfan syndrome Abnormal or missing connective tissue

Polydactyly extra fingers, toes, or both

Progeria Drastic premature aging

Neurofibromatosis Tumors of nervous system, skin

Patterns of InherItance Chapter 9 163

Hutchinson–Gilford progeria is an autosomal dominant disorder character- ized by drastically accelerated aging. It is usually caused by a mutation that affects lamin A, a protein component of intermediate filaments that support the nuclear envelope. In cells that carry this mutation, the nucleus is grossly abnormal, with improperly assembled nuclear pore complexes and membrane proteins on the wrong side of the nuclear envelope. The function of the nucleus as protector of chromosomes and gateway for transcription is severely impaired, and DNA damage accumulates quickly. The effects are pleiotropic. Outward symptoms begin to appear before age two, as skin that should be plump and resilient starts to thin, muscles weaken, and bones soften. Premature baldness is inevitable (Figure 9.17C). Most people with the disorder die in their early teens as a result of a stroke or heart attack brought on by hardened arteries, a condition typical of advanced age. Progeria does not run in families because affected people do not live long enough to reproduce.

The Autosomal Recessive Pattern A recessive allele on an autosome is expressed only in homozygous individuals, so traits associated with the allele tend to skip generations. They also appear in both sexes at equal frequency. Table 9.2 lists a few examples. Heterozygous individuals are called carriers because they have the allele but not the trait. Any child of two carriers has a 25 percent chance of inheriting the allele from both parents—and developing the trait (Figure 9.18A).

Albinism, a phenotype characterized by an abnormally low level of melanin, is inherited in an autosomal recessive pattern. Mutations associated with albinism affect proteins involved in melanin synthesis. Skin, hair, or eye pigmentation may be reduced or missing. In the most dramatic form, the skin is very white and does not tan, and the hair is white (Figure 9.18B). The irises of the eyes appear red because the lack of pigment allows underlying blood vessels to show through. Melanin also plays a role in the retina, so vision problems are typical. In skin, melanin acts as a sunscreen; without it, the skin is defenseless against UV radiation. Thus, people with the albino phenotype have a very high risk of skin cancer.

Figure 9.18 autosomal recessive inheritance. (B) © Rick Guidotti, Positive Exposure.

B. the albino phenotype is associated with autosomal reces- sive alleles that cause a deficiency in melanin.

AA Aa

Aa aa

A a

meiosis and gamete

formation

carrier mother carrier father

affected child

normal child

disorder-causing allele (recessive)

�Aa Aa

carrier child

a. only people homozygous for a recessive allele on an autosome have the associated trait. In this example, both parents are carriers. each of their children has a 25 percent chance of inheriting two recessive alleles, and being affected by the trait.

table 9.2 Some autosomal recessive traits in humans

trait Description

albinism absence of pigmentation

cystic fibrosis abnormally thick mucus damages tissues and organs

ellis–van creveld syndrome

Dwarfism, heart defects, polydactyly

friedreich’s ataxia Progressive loss of motor and sensory function

hereditary methemoglobinemia

Blue skin coloration

Phenylketonuria (PKU) Mental impairment

sickle-cell anemia red blood cells can sickle and disrupt circulation

tay–sachs disease Deterioration of mental and physical abilities; early death

With late-onset disorders, people may reproduce before symptoms appear, so the allele can be passed unknowingly to children.

164

Alleles associated with Tay–Sachs disease are inherited in an autosomal reces- sive pattern. In the general population, about 1 in 300 people is a carrier for one of these alleles, but the incidence is ten times higher in some groups, such as Jews of eastern European descent. The gene altered in Tay–Sachs encodes a lysosomal enzyme responsible for breaking down a particular type of lipid. Mutations result in an enzyme that misfolds and becomes destroyed, so cells make the lipid but cannot break it down. Typically, newborns homozygous for a Tay–Sachs allele seem normal, but within three to six months they become irritable, listless, and may have seizures as the lipid accumulates in their nerve cells. Blindness, deafness, and paralysis fol- low. Affected children usually die by age five (Figure 9.19).

The X-Linked Recessive Pattern Many genetic disorders are associated with alleles on the X chro- mosome (Figure 9.20 and Table 9.3). Almost all of them are inherited in a recessive pattern, probably because those caused by dominant X chromosome alleles tend to be lethal in male embryos.

A recessive allele on an X chromosome leaves two clues when it causes a genetic disorder. First, an affected father never passes the disorder to a son, because all children who inherit their father’s X chromosome are female (Figure 9.21A). Thus, a heterozygous female is always the bridge between an affected male and his affected grandson. Second, the disorder appears in males more often than in females. This is because all males who carry the allele have the disorder, but not all heterozygous females do. One of the two X chromosomes in each cell of a female is an inactive Barr body, so only about half of a heterozygous female’s cells express the recessive allele. The other half of her cells

express the dominant, normal allele that she carries on her other X chromosome, and this expression can mask the phenotypic effects of the recessive allele.

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration. It is caused by mutations in the X chromo- some gene for dystrophin, a protein that links actin microfilaments in cytoplasm to a complex of proteins in the plasma membrane. This complex structurally and functionally links the cell to basement membrane. When dystrophin is absent, the entire protein complex is unstable. Muscle cells, which are subject to stretching, are particularly affected. Their plasma membrane is easily damaged, and they become flooded with calcium ions. Eventually, the cells die and become replaced by fat cells and connective tissue. DMD affects about 1 in 3,500 people; almost all are boys. Symptoms begin between ages three and seven. Anti-inflammatory drugs can slow the progression of the disorder, but there is no cure. When an affected boy is about twelve years old, he will begin to use a wheelchair and his heart will start to fail. Even with the best care, he will probably die before the age of thirty, from a heart disorder or respiratory failure (suffocation).

Hemophilias are genetic disorders in which the blood does not clot properly. Most of us have a blood clotting mechanism that quickly stops bleeding from minor injuries. That mechanism involves two proteins, clotting factor VIII and IX, both products of X chromosome genes. Mutations in these two genes cause two types of

Figure 9.19 tay–Sachs disease. Conner Hopf was diagnosed with Tay–Sachs when he was 7 months old. He died before his second birthday. Courtesy of © Conner’s Way Foundation, www.connersway.com.

Figure 9.20 the human X chromosome. This chromosome carries about 1,900 genes —almost 10 percent of the total. Most X chromosome alleles that cause genetic disorders are inherited in a recessive pattern. A few disorders are listed (in parentheses).

IL2RG (SCID-X1)

XIST X chromosome inactivation control

(red-deficient color blind) (green-deficient color blind)

(hemophilia A)

(anhidrotic ectodermal dysplasia)

(hemophilia B)

dystrophin (muscular dystrophy)

polyploid Having three or more of each type of chromosome.

Inheriting more than two full sets of chromosomes is fatal in humans.

table 9.3 Some X-Linked traits in humans

Disorder or Abnormality Main Symptoms

Androgen insensitivity syndrome

XY individual has the traits of a female; sterility

Red–green color blindness Inability to distinguish red from green

fragile X syndrome Intellectual, emotional disability

Hemophilia Impaired blood clotting

Incontinentia pigmenti Abnormalities of skin, hair, teeth, nails, eyes

Muscular dystrophies Progressive loss of muscle function

SCID-X1 Severe immune system deficiency

X-linked anhidrotic dysplasia

Mosaic skin; other ill effects

PATTeRNS of INHeRITANCe ChAptER 9 165

hemophilia (A and B, respectively). Males who carry one of these mutations have prolonged bleeding, as do homozygous females (heterozygous females make enough clotting factor to have a clotting time that is close to normal). Affected people bruise easily, but internal bleeding is their most serious problem. Repeated bleeding inside the joints disfigures them and causes chronic arthritis. Today, about 1 in 7,500 people in the general population is affected. That number may be rising because the disorder is now treatable, and more affected people now live long enough to trans- mit a mutated allele to children.

Color blindness refers to a range of conditions in which an individual cannot distinguish among colors in the spectrum of visible light. These conditions are typi- cally inherited in an X-linked recessive pattern, because most of the genes involved in color vision are on the X chromosome. Humans can sense the differences among 150 colors, and this perception depends on pigment-containing receptors in the eyes. Mutations that result in altered or missing receptors affect color vision. For example, people who have red–green color blindness see fewer than 25 colors because recep- tors that respond to the red and green wavelengths of light are weakened or absent (Figure 9.21B,C). Some people with red–green color blindness confuse red and green, and others see green as gray.

Take-Home Message 9.7 how do we know whether a trait is associated with a dominant or recessive allele on an autosome or sex chromosome?

• With an autosomal dominant inheritance pattern, anyone with the allele (whether homozygous or heterozygous) has the associated trait. The trait characteristically appears in every generation.

• With an autosomal recessive inheritance pattern, only persons who are homozygous for an allele have the associated trait. The trait tends to skip generations.

• Men who have an X-linked allele have the associated trait, but not all heterozygous women do. Thus, the trait appears more often in men. Men transmit an X-linked allele to their daughters, but not to their sons.

9.8 Chromosome Number Changes REMEMBER: Researchers risk interpreting their results in terms of what they want to find out; sampling error can be a substantial problem when testing a small group (Section 1.6). Amyloid fibrils form insoluble deposits that disrupt brain function (2.9). Cells that are diploid (2n) have two sets of chromosomes (6.3). Meiosis reduces the chromosome number during gamete formation; the fusion of two haploid (n) gametes at fertilization restores the diploid chromosome number in the resulting zygote (8.5).

A polyploid individual has three or more complete sets of chromosomes. About 70 percent of flowering plant species are polyploid, as are some insects, fishes, and other animals—but not humans. In our species, inheriting more than two full sets of chromosomes is invariably fatal, although some somatic cells are normally polyploid in adult tissues. Aneuploidy—having too many or too few copies of a particular

Figure 9.21 X-linked recessive inheritance. (B) Photos by Gary L. Friedman, www.FriedmanArchives.com; (C) Life Nature Library, The Primates, 1965, Sarel Eimerl and Irven DeVore.

XX XY

X Y

meiosis and gamete

formation

carrier mother normal father

3XX XY

normal daughter or son

carrier daughter

affected son

recessive allele on X chromosome

B. A view of color blindness. The image on the left shows how a person with red–green color blindness sees the image on the right. The perception of blues and yellows is normal; red and green appear similar.

A. In this example of X-linked inheritance, the mother carries a recessive allele on one of her two X chromo- somes (red ).

C. Part of a standardized test for color blindness. A set of 38 of these circles is commonly used to diagnose deficiencies in color perception. You may have one form of red–green color blindness if you see a 7 instead of a 29 in the circle on the left. You may have another form of red–green color blindness if you see a 3 instead of an 8 in the circle on the right.

166 Unit 2 GeNeTICS

Telophase II

Anaphase II

Metaphase II

Telophase I

Anaphase I

Metaphase I

Figure 9.22 An example of nondisjunction during meiosis. of the two pairs of homologous chromosomes shown here, one fails to separate during anaphase I. The chro- mosome number is altered in the resulting gametes.

Figure it Out: During which stage of meiosis does nonjunction occur in this example?

Answer: Anaphase I chromosome—does occur in humans. A few babies (less than 1 percent) are born with a diploid chromosome number that differs from the normal 46. Changes in chromosome number are usually an outcome of nondisjunction, the failure of chromosomes to separate properly during mitosis or meiosis. Nondisjunction during meiosis (Figure 9.22) can affect chromosome number at fertilization. For example, if a normal gamete (n) fuses with a gamete that has an extra chromosome (n1), the resulting zygote will have three copies of one type of chromosome and two of every other type (2n1), an aneuploid condition called trisomy. If a normal gamete (n) fuses with a gamete missing a chromosome (n1), the new individual will have one copy of one chromosome and two of every other type (2n1), an aneuploid condition called monosomy. A few disorders associated with aneuploidy are listed in Table 9.4.

Autosomal Change and Down Syndrome In most cases, inheriting the wrong number of autosomes is fatal in humans before birth or shortly thereafter. An important exception is trisomy 21. A person born with three chromosomes 21 will have Down syndrome and a high likelihood of surviving infancy. Mild to moder- ate mental impairment and health problems such as heart disease are hallmarks of this syndrome. Other effects may include a somewhat flattened facial profile, a fold of skin that starts at the inner corner of each eyelid, white spots on the iris (Fig- ure 9.23), and one deep crease (instead of two shallow creases) across each palm. The skeleton grows and develops abnormally, so older children have short body parts, loose joints, and misaligned bones of the fingers, toes, and hips. Muscles and reflexes are weak, and motor skills such as speech develop slowly. Early training can help these individuals learn to care for themselves and to take part in normal activities. By age 40, all persons with Down syndrome will begin to have symptoms of Alzheimer’s disease, a condition of progressive mental deterioration. A gene on chromosome 21 is the culprit. Having three of these chromosomes, a person with Down syndrome makes an excess of the gene’s product, a protein that forms the main component of amyloid fibrils characteristic of Alzheimer’s. Down syndrome occurs in about 1 of 700 live births, and the risk increases with maternal age.

Change in the Sex Chromosome Number About 1 in 400 human babies is born with an atypical number of sex chromosomes. Most often, such alterations lead to mild difficulties in learning and impaired motor skills such as a speech delay, but these problems may be very subtle.

About 1 in 2,500 girls is born with Turner syndrome, an outcome of having an X chromosome and no corresponding X or Y chromosome (XO). This aneu- ploid condition is thought to arise most frequently with an unstable Y chromo- some inherited from the father. The zygote starts out being genetically male, with an X and a Y chromosome. The Y chromosome breaks up and is lost during early development, so the embryo continues to develop as a female. Affected individuals grow up well proportioned but a bit short, with an average height of 4 feet 8 inches (1.4 meters). Extra folds of skin on the neck, mild skeletal abnormalities, and heart defects are common. The ovaries do not develop properly, so these individuals do not make enough sex hormones to become sexually mature or develop secondary sexual traits such as enlarged breasts. Hormone therapy can trigger sexual develop- ment, but even with treatment most girls affected by the syndrome are infertile.

A female may inherit multiple X chromosomes, a condition called triple X syn- drome or trisomy X. This syndrome occurs in about 1 of 1,000 births; as with Down syndrome, risk increases with maternal age. Only one X chromosome is typically

PATTeRNS of INHeRITANCe ChAptER 9 167

nondisjunction failure of chromosomes to separate properly during nuclear division.

Figure 9.23 Down syndrome, genotype and phenotype. (A) L. Willatt, East Anglian Regional Genetics Service/Science Source; (B) Ciarra, photo by © Michelle Harmon.

table 9.4 Some traits Associated With Chromosome number Changes

Disorder or Abnormality Main Symptoms

Down syndrome Mental impairment; heart defects

Turner syndrome (Xo) Sterility; abnormal ovaries, abnormal sexual traits

Klinefelter syndrome (XXY)

Sterility, mental impairment

XXX syndrome Minimal abnormalities

XYY syndrome Mild mental impairment

Take-Home Message 9.8 What are the effects of chromosome number changes in humans?

• Polyploidy is fatal in humans, but not in some other organisms. • Aneuploidy can arise from nondisjunction during meiosis. In humans, most cases of

aneuploidy are associated with some degree of mental impairment.

active in female cells, so having extra X chromosomes usually does not cause physi- cal or medical problems, but mild mental impairment may occur.

About 1 out of every 500 males has two or more X chromosomes (XXY, XXXY, and so on). The resulting disorder, Klinefelter syndrome, develops at puberty. As adults, affected males tend to be overweight and tall, with small testes. Underpro- duction of the hormone testosterone interferes with sexual development and can result in sparse facial and body hair, a high-pitched voice, enlarged breasts, and infertility. Testosterone injections during puberty can minimize some of these traits.

About 1 in 1,000 males is born with an extra Y chromosome (XYY), a result of nondisjunction of the Y chromosome during sperm formation. Adults affected by the resulting XYY syndrome tend to be taller than average, but are within a normal range of phenotype. Sexual development occurs normally, and fertility is normal. Having XYY syndrome was once thought to predispose an individual to a life of crime. This misguided view was based on sampling error (too few cases in nar- rowly chosen groups such as prison inmates) and bias (the researchers who gathered the karyotypes also took the personal histories of the participants). That view has since been disproven: Men with XYY syndrome are only slightly more likely to be convicted for crimes than other men. Researchers believe this slight increase can be explained by poor socioeconomic conditions related to mild mental impairment of individuals with the syndrome.

B. example of a Down syndrome phenotype. excess tissue deposits on the iris give rise to a ring of starlike white speckles, a lovely effect of the chromosome number change that causes Down syndrome.

A. example of a Down syndrome genotype.

168 Unit 2 GeNeTICS

A. Conventional ultrasound.

B. 4D ultrasound.

C. fetoscopy.

Figure 9.24 three ways of imaging a human fetus. (A) Mediscan/Corbis; (B) Dr. Benoit/Mona Lisa/LooksatSciences/Phototake; (C) © Neil Bromhall/Science Source.

9.9 Genetic Screening REMEMBER: Cells make the thousands of different proteins they need from only twenty kinds of amino acid monomers (Section 2.9). During early development, an embryo’s cells start using different subsets of their DNA, thus becoming different in form and function—a process called differentiation (6.1).

Studying human inheritance patterns has given us many insights into how genetic disorders arise and progress, and how to treat them. Surgery, prescription drugs, hormone replacement therapy, and dietary controls can minimize and in some cases eliminate the symptoms of a genetic disorder. Some disorders can be detected early enough to start countermeasures before symptoms develop. For these reasons, most hospitals in the United States now screen newborns for mutations that cause phenylketonuria, or PKU. The mutations affect an enzyme that converts one amino acid (phenylalanine) to another (tyrosine). Without this enzyme, the body becomes deficient in tyrosine, and phenylalanine accumulates to high levels. The imbalance inhibits protein synthesis in the brain, which in turn results in severe neurologi- cal symptoms. Restricting all intake of phenylalanine can slow the progression of PKU, so routine early screening has resulted in fewer individuals suffering from the symptoms of the disorder.

Parents can also benefit from human genetics studies. The probability that a future child will inherit a genetic disorder can be estimated by testing prospective parents for alleles known to be associated with genetic disorders. Karyotypes and pedigrees are also useful in this type of screening, which can help people make informed decisions about family planning.

Genetic screening is also done post-conception, in which case it is called pre- natal diagnosis (prenatal means before birth). Prenatal diagnosis checks an embryo or fetus for physical and genetic abnormalities. Early diagnosis of these conditions gives parents time to prepare for the birth of an affected child, and an opportunity to decide whether to continue with the pregnancy or terminate it. Dozens of condi- tions are detectable prenatally, including aneuploidy, hemophilia, Tay–Sachs disease, sickle-cell anemia, muscular dystrophy, and cystic fibrosis. If a disorder is treatable, early detection can allow the newborn to receive prompt and appropriate treatment. A few conditions are even surgically correctable before birth.

As an example of how prenatal diagnosis works, consider a woman who becomes pregnant at age thirty-five. Her doctor will probably perform a procedure called obstetric sonography, in which ultrasound waves directed across the woman’s abdomen form images of the fetus’s limbs and internal organs (Figure 9.24A,B). If the images reveal a physical defect that may be the result of a genetic disorder, a more invasive technique such as fetoscopy would be recommended for further diagnosis. With fetoscopy, sound waves pulsed from inside the mother’s uterus yield images much higher in resolution than ultrasound (Figure 9.24C). Samples of tissue or blood are often taken at the same time, and some corrective surgeries can be performed.

Human genetics studies show that our thirty-five-year-old woman has about a 1 in 80 chance that her baby will be born with a chromosomal abnormality, a risk more than six times greater than when she was twenty years old. Thus, even if no abnormalities are detected by ultrasound, she probably will be offered an additional diagnostic procedure, amniocentesis, in which a small sample of fluid is drawn from the amniotic sac enclosing the fetus (Figure 9.25A). The fluid contains cells shed by the fetus, and those cells can be tested for genetic disorders. Chorionic villus sampling (CVS) can be performed earlier than amniocentesis. With this technique,

PATTeRNS of INHeRITANCe ChAptER 9 169

Take-Home Message 9.9 how do we use what we know about human inheritance?

• Studying inheritance patterns for genetic disorders has helped researchers develop treatments for some of them.

• Genetic testing can provide prospective parents with information about the health of their future children.

A. With amniocentesis, a tiny bit of the fluid inside the amniotic sac is removed, and fetal cells that have been shed into the fluid are tested for genetic disorders. Cho- rionic villus sampling tests cells of the chorion, which is part of the placenta.

B. About 48 hours after in vitro fertilization, a human embryo is a ball of eight identical cells. If one cell is removed for genetic analysis, the remaining seven can continue development.

Figure 9.25 Cells tested for prenatal and preimplanta- tion diagnosis. (A) © Lennart Nilsson/Bonnierforlagen AB; (B) Fran Heyl Associates © Jacques Cohen, computer-enhanced by © Pix Elation.

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a few cells from the chorion are removed and tested (the chorion is a membrane that surrounds the amniotic sac and helps form the placenta, an organ that allows substances to be exchanged between mother and embryo).

An invasive procedure often carries a risk to the fetus. The risks vary by the procedure. Amniocentesis has improved so much that, in the hands of a skilled phy- sician, it no longer increases the risk of miscarriage. CVS occasionally disrupts the placenta’s development and thus causes underdeveloped or missing fingers and toes in 0.3 percent of newborns. Fetoscopy raises the miscarriage risk by a whopping 2 to 10 percent, so it is rarely performed unless surgery or another medical procedure is required before the baby is born.

Couples who discover they are at high risk of having a child with a genetic disorder may opt for reproductive interventions such as in vitro fertilization. With this procedure, sperm and eggs taken from the prospective parents are mixed in a test tube. If an egg becomes fertilized, the resulting zygote will begin to divide. In about forty-eight hours, it will have become an embryo that consists of a ball of eight cells (Figure 9.25B). All of the cells in this ball have the same genes, but none has yet committed to being specialized one way or another. Doctors can remove one of these undifferentiated cells and analyze its genes, a procedure called preimplanta- tion diagnosis. The withdrawn cell will not be missed. If the embryo has no detect- able genetic defects, it is inserted into the woman’s uterus to develop. Most of the resulting “test-tube babies” are born in good health.

summary Section 9.1 symptoms of cystic fibrosis are pleiotropic effects of mutations in one gene. the allele associated with most cases persists at high frequency despite its devastating effects in homozygous people. carrying the allele may offer heterozygous individuals protection

from dangerous gastrointestinal tract infections.

Section 9.2 Gregor Mendel indirectly discovered the role of genes and alleles in inheritance by breeding pea plants and carefully tracking traits of the offspring over many generations. each gene occurs at a particular location on a chromosome. Individuals with

identical alleles are homozygous for the allele. Heterozygous individuals have two nonidentical alleles.

a dominant allele masks the effect of a recessive allele partnered with it on the homologous chromosome. Genotype (an individual’s particular set of alleles) gives rise to phenotype (the individual’s observable traits).

Section 9.3 Diploid cells have pairs of genes on homologous chromosomes. the two genes of a pair (which may differ as alleles) are separated from each other during meiosis, so they end up in different gametes. crossing individuals that breed

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Summary (continued) true for two forms of a trait yields offspring that are identically heterozygous for alleles governing the trait. a cross between such offspring is a monohybrid cross. the frequency at which the two forms of the trait appear among the offspring of a monohybrid cross can reveal a dominance relationship between the alleles.

In most cases, the two genes of a pair on homologous chromosomes are distributed into gametes independently of other gene pairs on other chromosomes. crossing individuals that breed true for two forms of two traits yields offspring that are identically heterozygous for alleles governing those traits. a cross between such offspring is a dihybrid cross. the frequency at which the two forms of the two traits appear among the offspring of such crosses can reveal dominance relationships between the alleles.

a Punnett square can be useful for determining the probability that certain genotypes (and phenotypes) will appear among the offspring of a monohybrid cross or a dihybrid cross.

Section 9.4 not all traits have a Mendelian inheritance pattern. With incomplete dominance, the phenotype of heterozygous individuals is an inter mediate blend of the two homozygous phenotypes. With codominance, heterozygous individuals have both homozygous

phenotypes. With epistasis, two or more genes affect the same trait. With pleiotropy, one gene affects two or more traits.

Section 9.5 environmental factors can influence phenotype by altering gene expression. a trait that is influenced by multiple genes often occurs in a range of pheno type called continuous variation. continu ous variation typically occurs as a bell curve in the range

of values. Multiple alleles such as those that arise in regions of short tandem repeats can give rise to continuous variation.

Section 9.6 Geneticists study inheritance patterns in humans by tracking genetic disorders and abnormalities through generations of families. a genetic abnormality is an uncommon version of a heritable trait that does not result in medical problems.

a genetic disorder sooner or later causes mild or severe medical problems (which often occur in a syndrome). Pedigrees can reveal inheritance patterns for alleles that can be predictably associated with specific phenotypes.

Section 9.7 an allele is inherited in an autosomal dominant pattern if the trait it specifies appears in everyone who carries it, and both sexes are affected with equal frequency. such traits appear in every generation of families that have the allele. an allele is

inherited in an autosomal recessive pattern if the trait it specifies

appears only in homozygous people. such traits also appear in both sexes equally, but they can skip generations.

an allele is inherited in an X-linked pattern when it occurs on the X chromosome. Most X-linked disorders are inherited in a recessive pattern, and these tend to appear in men more often than in women. heterozygous women have a dominant, normal allele that can mask the effects of the recessive one; men do not. Men can transmit an X-linked allele to their daughters, but not to their sons. only a woman can pass an X-linked allele to a son.

Section 9.8 occasionally, new individuals end up with the wrong chromosome number. consequences of such changes range from minor to lethal alterations in form and function.

chromosome number change is usually an outcome of nondisjunction, in which chromosomes fail to separate properly during nuclear division. Polyploid individuals have three or more of each type of chromosome. Polyploidy is lethal in humans, but not in flowering plants and some insects, fishes, and other animals.

In humans, most cases of autosomal aneuploidy are lethal. trisomy 21, which causes Down syndrome, is an exception. some changes in the number of sex chromosomes result in an impairment in learning and motor skills.

Section 9.9 Prospective parents can use genetic screening to estimate their risk of transmitting a harmful allele to offspring. the procedure involves analysis of parental pedigrees and genotype by a genetic counselor. amniocentesis and other methods

of prenatal testing can reveal a genetic disorder before birth.

Answers in Appendix i

1. a heterozygous individual has a for a trait being studied. a. pair of identical alleles b. pair of nonidentical alleles c. haploid condition, in genetic terms

2. an organism’s observable traits constitute its . a. phenotype c. genotype b. variation d. pedigree

self-Quiz

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1. Mendel crossed a true-breeding pea plant with green pods and a true-breeding pea plant with yellow pods. all offspring had green pods. Which color is recessive?

2. assuming that independent assortment occurs during meiosis, what type(s) of gametes will form in individuals with the follow- ing genotypes?

a. AABB c. Aabb b. AaBB d. AaBb

3. refer to problem 2. Determine the frequencies of each geno- type among offspring from an AABB 3 aaBB cross.

4. Duchenne muscular dystrophy (DMD), which is inherited in an X-linked recessive pattern, occurs almost exclusively in males. suggest why.

5. heterozygous individuals perpetuate some alleles that have lethal effects in homozygous individuals. a mutated allele (ML)

associated with taillessness in Manx cats is an example (left). cats homozygous for this allele (MLML) typically die before birth due to severe spinal cord defects. In a case of incomplete dominance, cats heterozygous for the ML

allele and the normal, unmutated allele (M) have a short, stumpy tail or none at all. two MLM cats mate. What is the probability that any one of their surviving kittens will be heterozygous?

3. the offspring of the cross AA 3 aa are . a. all AA c. all Aa b. all aa d. 1/2 AA and 1/2 aa

4. the probability of a crossover occurring between two genes on the same chromosome . a. is unrelated to the distance between them b. decreases with the distance between them c. increases with the distance between them

5. If one parent is heterozygous for a dominant allele on an autosome and the other parent does not carry the allele, any child of theirs has a chance of being heterozygous. a. 25 percent b. 50 percent c. 75 percent

6. true or false? all traits are inherited in a Mendelian pattern.

7. one gene that affects three traits is an example of . a. dominance c. pleiotropy b. codominance d. epistasis

8. in a trait is indicated by a bell curve. a. an epigenetic effect c. Incomplete dominance b. nondisjunction d. continuous variation

9. Pedigree analysis is necessary when studying human inheritance patterns because . a. humans have approximately 20,000 genes b. of ethical problems with experimenting on humans c. inheritance in humans is more complicated than it is in

other organisms d. genetic disorders occur only in humans e. all of the above

10. a female child inherits one X chromosome from her mother and one from her father. What sex chromosome does a male child inherit from each of his parents?

11. nondisjunction at meiosis can result in . a. base-pair substitutions c. crossing over b. aneuploidy d. pleiotropy

12. true or false? an individual with three or more complete sets of chromosomes is polyploid.

13. Klinefelter syndrome (XXY) is most easily diagnosed by . a. pedigree analysis c. karyotyping b. aneuploidy d. a Punnett square

14. Match each example with the best description. dihybrid cross a. bb monohybrid cross b. AaBb 3 AaBb homozygous c. Aa heterozygous d. Aa 3 Aa

15. Match the terms appropriately. polyploid a. symptoms of a genetic disorder syndrome b. extra sets of chromosomes aneuploidy c. caused by a short tandem repeat Mendelian d. one extra chromosome genotype e. dominant > recessive huntington’s f. an individual’s alleles disease

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10.1 Personal Genetic Testing 174

10.2 Finding Needles in Haystacks 175

10.3 Studying DNA 178

10.4 Genetic Engineering 181

10.5 Modifying Humans 184

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174 Unit 2 Genetics

10.1 Personal Genetic Testing REMEMBER: some lipoproteins consist of variable amounts and types of proteins and lipids (section 2.9). A base-pair substitution is a mutation in which one nucleo- tide replaces another (7.6). BRCA1 mutations give rise to neoplasms (8.3). Alleles may encode slightly different forms of a gene’s product, and such differences influ- ence the details of traits shared by a species (8.4). A heterozygous individual has two nonidentical alleles of a gene (9.2). A person who is homozygous for a mutated allele of the MC1R gene makes only the reddish type of melanin, so this individual has red hair; most other human traits are polygenic, and many have epigenetic contributions (9.6). Alzheimer’s disease is a condition of progressive mental deterioration (9.8).

About 99 percent of your DNA is exactly the same as everyone else’s. The shared part is what makes you human; the differences make you a unique member of the species. If you compared your DNA with your neighbor’s, about 2.97 billion nucleotides of the two sequences would be identical; the remaining 30 million nonidentical nucleo- tides are sprinkled throughout your chromosomes. The sprinkling is not entirely ran- dom because some regions of DNA vary less than others; these conserved regions are of particular interest to researchers because they are most likely to have an essential function. If a conserved sequence does vary among people, the variation tends to be in single nucleotides at a particular location. A base-pair substitution that is car- ried by a measurable percentage of a population, usually above 1 percent, is called a single-nucleotide polymorphism, or SNP (pronounced “snip”).

Alleles of most genes differ by single nucleotides, and differences in alleles are the basis of the variation in human traits that makes each individual unique. Thus,

SNPs account for many of the differences in the way humans look, and they also have a lot to do with differences in the way our bodies work— how we age, respond to drugs, weather assaults by pathogens and toxins, and so on. Finding out which ones you carry has never been easier. Genetic testing companies can extract your DNA from a few drops of spit or a cheek swab, then analyze it using a tiny glass plate called a SNP- chip (Figure 10.1A). Results may include the predicted likelihood of having traits associated with your particular SNPs. For example, the test will probably determine whether you are homo- zygous for one allele of the MC1R gene. If you are, then you have red hair. Few SNPs have such a clear effect, however. Most human traits arise from a complex interplay of genes and environ- mental factors that we are still unraveling. Thus, although a DNA test can reliably determine an individual’s SNPs, it cannot reliably predict the effect of most of those SNPs on the individual.

Consider the lipoprotein particles that carry fats and cholesterol through our bloodstreams. These particles consist of variable amounts and types of lipids and proteins, one of which is specified by the gene APOE. About one in four people carries an allele of this gene, E4, that increases the risk of developing Alzheimer’s disease later in life. If you are heterozygous for this allele, a DNA testing company

Figure 10.1 Personal genetic tests. (A) Image courtesy of Illumina, Inc.; (B) © Oli Scarff/Getty Images.

A. Only about 1 percent of the 3 billion bases in a person’s DnA are unique to the individual. Personal genetic testing companies use chips like this one to analyze their custom- ers’ chromosomes for snPs. this chip reveals which versions of 4,301,331 snPs occur in the DnA of four individuals at a time.

B. celebrity Angelina Jolie chose preventive treatment after genetic testing showed she had a very high risk of breast cancer. she carries a BRCA1 mutation associated with an 87% lifetime risk of developing breast cancer. even though Jolie did not yet have cancer, she underwent a double mas- tectomy, thereby reducing her risk of breast cancer to 5%.

Personalized genetic testing is already beginning to revolutionize medicine.

Application

BiOTEcHNOlOGy ChAPtER 10 175

cannot tell you whether you will develop Alzheimer’s. However, it may report your lifetime risk of developing the disease, which is about 30 percent, as compared with about 14 percent for someone who has no E4 allele.

What, exactly, does a 30 percent lifetime risk of Alzheimer’s disease mean? The number is a probability statistic; it means, on average, 3 of every 10 people who have one E4 allele eventually get the disease. However, a risk is just that. Not everyone who has an E4 allele develops Alzheimer’s, and not everyone who develops the disease has the allele. Other unknown factors, including epigenetic modifications of DNA, contribute to the disease. We still have a limited understanding of how genes contribute to many health conditions, particularly age-related ones such as Alzheimer’s disease. Geneticists believe that it will be at least five to ten more years before genotyping can be used to accurately predict an individual’s future health problems. Nonetheless, we are at a tipping point; personalized genetic testing is already beginning to revolutionize medicine. Cancer treatments are now being tailored to fit the genetic makeup of individual patients. People who discover they carry alleles associated with a heightened risk of a medical condition are being encouraged to make lifestyle changes that could delay the condition’s onset or prevent it entirely. Preventive treatments based on personal genetics are becoming more common—and more mainstream (Figure 10.1B).

10.2 Finding Needles in Haystacks REMEMBER: A tracer has a detectable component (Section 2.2). Typical prokaryotes have plasmids that carry a few genes (3.4). cloning technologies produce identical copies of an organism (6.1). A bacteriophage infects a bacterium by injecting DNA into it; hydrogen bonds between bases hold the two strands of DNA together in a double helix (6.2). Hybridization is the spontaneous establishment of base-pairing between nucleic acid strands; primers are short, single strands of nucleotides; DNA ligase seals gaps in DNA strands during DNA replication (6.4).

Cutting and Pasting DNA In the 1950s, excitement over the discovery of DNA’s structure gave way to frustration: No one could determine the order of nucleotides in a molecule of DNA. Identifying a single nucleotide among thousands or mil- lions of others turned out to be a huge technical hurdle. Research in a seemingly unrelated field yielded a solution when Werner Arber, Hamilton Smith, and their coworkers discovered how some bacteria resist infection by bacteriophages. These bacteria have enzymes that chop up any injected viral DNA before it has a chance to integrate into the bacterial chromosome. The enzymes restrict viral growth; hence their name, restriction enzymes. A restriction enzyme cuts DNA wherever a specific nucleotide sequence occurs (Figure 10.2). For example, the enzyme EcoRI (named after E. coli, the bacteria from which it was isolated) cuts DNA at the nucle- otide sequence GAATTC

. Other restriction enzymes cut at different sequences. The discovery of restriction enzymes allowed researchers to cut chromosomal

DNA into manageable chunks. It also allowed them to combine DNA fragments from different organisms. How? Many restriction enzymes, including EcoRI, leave single-stranded tails on DNA fragments

. Researchers realized that complemen- tary tails will base-pair, regardless of the source of the DNA

. The tails are called “sticky ends,” because two DNA fragments stick together when their matching tails base-pair. DNA ligase can be used to seal the gaps between base-paired sticky ends, so continuous DNA strands form

. Thus, using appropriate restriction enzymes

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When the DNA fragments from the two sources are mixed together, matching sticky ends base-pair.

DNA ligase joins the base-paired DNA fragments to produce molecules of recombinant DNA.

The enzyme cuts the DNA into fragments. Eco Ri leaves single-stranded tails (“sticky ends”).

The restriction enzyme Eco Ri recognizes the nucleo- tide sequence GAATTc in DNA from two sources.

restriction enzyme Type of enzyme that cuts DNA at a specific nucleotide sequence.

single-nucleotide polymorphism (SnP) A one- nucleotide DNA sequence variation carried by a measurable percentage of a population.

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and DNA ligase, researchers can cut and paste DNA from different sources. The result, a hybrid molecule that consists of genetic material from two or more organ- isms, is called recombinant DNA.

Making recombinant DNA is the first step in DNA cloning, a set of laboratory methods that uses living cells to mass-produce specific DNA fragments. Researchers clone a fragment of DNA by inserting it into a cloning vector, which is a molecule that can carry foreign DNA into host cells. Bacterial plasmids may be used as clon- ing vectors, for example (Figure 10.3). When a bacterium reproduces, its offspring inherit a full complement of genetic information—one chromosome plus plasmids. If a plasmid carries a fragment of foreign DNA, that fragment gets copied and distributed to descendant cells along with the plasmid DNA. A host cell into which a recombinant cloning vector has been inserted can be grown in the laboratory (cul- tured) to yield a huge population of genetically identical cells. Each of these clones contains a copy of the vector and the inserted DNA fragment. The hosted DNA fragment can be harvested in large quantities from the clones.

DNA Libraries The entire set of genetic material—the genome—of most organ- isms consists of thousands of genes. To study or manipulate a single gene, research- ers first find it, and then separate it from all of the other genes in a genome. They often begin by cutting an organism’s DNA into fragments, and then cloning all the fragments. The result is a set of clones that collectively contain all of the DNA in a genome. A set of cells that hosts various cloned DNA fragments is a DNA library.

In DNA libraries, a cell that contains a particular DNA fragment of interest is mixed up with thousands or millions of others that do not—a needle in a genetic haystack. One way to find that one clone among the others involves the use of a probe, a fragment of DNA or RNA labeled with a tracer. For example, to find a targeted gene, researchers may use radioactive nucleotides to synthesize a short strand of DNA complementary in sequence to a similar gene. Because the nucleo- tide sequences of the probe and the gene are complementary, the two can hybridize. When the probe is mixed with DNA from a library, it will hybridize with the gene, but not with other DNA. Researchers can pinpoint a cell that hosts the gene by detecting the label on the probe. That cell is isolated and cultured, and DNA can be extracted in bulk from the cultured cells for research or other purposes.

Figure 10.3 An example of cloning. Here, a fragment of chromosomal DNA is inserted into a plasmid.

A. A restriction enzyme (gold triangles) cuts a specific nucleotide sequence in chromosomal DNA and also in a plasmid cloning vector.

B. A fragment of chromosomal DNA and the cut plasmid base-pair at their sticky ends. DNA ligase joins the two pieces of DNA, so a recom- binant plasmid forms.

C. The recombinant plasmid is inserted into a host bacterial cell. When the cell reproduces, it copies the plasmid along with its chromosome. Each descendant cell receives a plasmid.

cloning vector A DNA molecule that can accept foreign DNA and be replicated inside a host cell.

DnA cloning Set of methods that uses living cells to mass-produce targeted DNA fragments.

DnA library collection of cells that host different fragments of foreign DNA, often representing an organism’s entire genome.

genome An organism’s complete set of genetic material.

PCR Polymerase chain reaction. Method that rapidly generates many copies of a specific section of DNA.

probe Fragment of DNA or RNA labeled with a tracer; can hybridize with a nucleotide sequence of interest.

recombinant DnA A DNA molecule that contains genetic material from more than one organism.

recombinant plasmid

plasmid cloning vector

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BiOTEcHNOlOGy ChAPtER 10 177

PCR The polymerase chain reaction (PCR) is a technique used to mass-produce copies of a particular section of DNA without having to clone it in living cells (Fig- ure 10.4). The reaction can transform a needle in a haystack—that one-in-a-million fragment of DNA—into a huge stack of needles with a little hay in it.

The starting material for PCR is any sample of DNA with at least one molecule of a targeted sequence. It might be extracted from a mixture of 10 million different clones, a sperm, a hair left at a crime scene, or a mummy—essentially any sample that has DNA in it.

The PCR reaction is similar to DNA replication. It requires two synthetic DNA primers, each designed to base-pair with one end of the section of DNA to be amplified, or mass-produced

. Researchers mix these primers with the starting (template) DNA, nucleotides, and DNA polymerase, then expose the reaction mix- ture to repeated cycles of high and low temperatures. A few seconds at high temper- ature disrupts the hydrogen bonds that hold two strands of DNA together, so every molecule of DNA unwinds and becomes single-stranded. As the temperature of the reaction mixture is lowered, the single DNA strands hybridize with the primers

. The DNA polymerases of most organisms denature at the high temperature

required to separate DNA strands. The kind that is used in PCR reactions, Taq poly- merase, is from Thermus aquaticus. This bacterial species lives in hot springs and hydrothermal vents, so its DNA polymerase necessarily tolerates heat. Taq poly- merase, like other DNA polymerases, recognizes hybridized primers as places to start DNA synthesis

. Synthesis proceeds along the template strand until the tem- perature rises and the DNA separates into single strands

. The newly synthesized DNA is a copy of the targeted section. When the mixture is cooled, the primers rehybridize, and DNA synthesis begins again. Each cycle of heating and cooling takes only a few minutes, but it can double the number of copies of the targeted sec- tion of DNA

. Thirty PCR cycles may amplify that number a billionfold.

Figure 10.4 two rounds of PCR. Each cycle of this reaction can double the number of copies of a targeted sequence of DNA. Thirty cycles can make a billion copies.

DNA (blue) with a targeted sequence is mixed with primers (pink), nucleotides, and heat-tolerant Taq DNA polymerase.

targeted section

When the mixture is heated, the double-stranded DNA separates into single strands. When the mixture is cooled, some of the primers base-pair with the DNA at opposite ends of the targeted sequence.

targeted section

The mixture is heated again, so all double- stranded DNA separates into single strands. When it is cooled, primers base-pair with the targeted sequence in the original template DNA and in the new DNA strands.

Each cycle of heating and cooling can double the number of copies of the targeted DNA section.

targeted section

Taq polymerase begins DNA synthesis at the prim- ers, so it produces complementary strands of the targeted DNA sequence.

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Take-Home Message 10.2 What techniques allow researchers to study DnA?

• DNA cloning uses living cells to mass-produce particular DNA fragments. Restriction enzymes cut DNA into fragments, then DNA ligase seals the fragments into cloning vectors. Recombinant DNA molecules result.

• A cloning vector that holds foreign DNA can be introduced into a living cell. When the host cell divides, it gives rise to huge populations of genetically identical cells (clones), each of which contains a copy of the foreign DNA.

• Researchers can isolate one gene from the many others in a genome by making a DNA library. A probe can be used to identify one clone that hosts a targeted DNA frag- ment among many other clones in the library.

• PcR quickly mass-produces copies of a targeted section of DNA.

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10.3 Studying DNA REMEMBER: A fat is a substance that consists mainly of triglycerides (Section 2.8). James Watson and Francis crick built the first accurate model of the DNA molecule in 1953 (6.2). in DNA replication, DNA polymerases begin assembling new strands of DNA at hybridized primers; for each molecule of DNA that is copied, two DNA molecules are produced, each a duplicate of the parent—one strand is new, and the other is parental (6.4). A knockout is an organism in which a gene has been deliberately inactivated (7.7). A short tandem repeat is a series of a few nucleotides repeated several times in a row in chromosomal DNA (9.5).

Sequencing the Human Genome Once a fragment of DNA has been isolated (for example by cloning or PCR), researchers can use a technique called sequenc- ing to determine the order of nucleotides in it. The most common method uses DNA polymerase. This enzyme is mixed with a primer, nucleotides, and the DNA to be sequenced (the template). Starting at the primer, the polymerase joins the nucleotides into a new strand of DNA, in the order dictated by the sequence of the template. The DNA fragments are then separated by length. In a technique called electrophoresis, an electric field pulls the fragments through a semisolid gel. Fragments of different sizes move through the gel at different rates. The shorter the fragment, the faster it moves, because shorter fragments slip through the tangled molecules of the gel faster than longer fragments do. All fragments of the same length move through the gel at the same speed, so they gather into bands. The order of the bands in the gel reflects the sequence of the template DNA (Figure 10.5A).

The sequencing method we have just described was invented in 1975. Ten years later, it had become so routine that scientists began to consider sequencing the entire human genome—all 3 billion nucleotides. Proponents of the idea said it could provide huge payoffs for medicine and research. Opponents said this daunting task would divert attention and funding from more urgent research. It would require 50 years to sequence the human genome given the techniques of the time. However, the techniques continued to improve rapidly, and with each improvement more nucleotides could be sequenced in less time. Automated (robotic) DNA sequencing and PCR had just been invented. Both were still too cumbersome and expensive to be useful in routine applications, but they would not be so for long. Waiting for faster, cheaper technologies seemed the most efficient way to sequence the genome, but just how fast did they need to be before the project should begin?

A few privately owned companies decided not to wait, and started sequenc- ing. One of them intended to determine the genome sequence in order to patent it. The idea of patenting the human genome provoked widespread outrage, but it also spurred commitments in the public sector. In 1988, the National Institutes of Health (NIH) essentially took over the project by hiring James Watson (of DNA structure fame) to head an official Human Genome Project, and providing $200 million per year to fund it. A partnership formed between the NIH and international institu- tions that were sequencing different parts of the genome. Watson set aside 3 percent of the funding for studies of ethical and social issues arising from the work. He later resigned over a patent disagreement, and geneticist Francis Collins took his place.

Amid ongoing squabbles over patent issues, Celera Genomics formed in 1998. With biologist Craig Venter at its helm, the company intended to commercial- ize human genetic information. Celera invented faster techniques for sequencing genomic DNA because the first to have the complete sequence had a legal basis for patenting it. The competition motivated the international partnership to accelerate

DnA profiling identifying an individual by analyzing the unique parts of his or her DNA.

electrophoresis Technique that separates DNA frag- ments by size.

genomics The study of genomes.

sequencing Method of determining the order of nucleotides in DNA.

Figure 10.5 Sequencing, a method of determining the nucleotide sequence of a DnA molecule. (A) Patrick Landmann/Science Source; (B) © Michelle McLoughlin/Reuters/Corbis.

A. Human DNA sequence data. On this computer screen, the four nucleotides (adenine, thymine, guanine, and cytosine) are color-coded green, red, yellow, and blue. The order of colored bands in each vertical “lane” repre- sents part of the sequence of the template DNA.

B. Today’s automated DNA sequencing machines can sequence an individual’s entire genome in 2–4 hours, for a cost of about $1,000.

BiOTEcHNOlOGy ChAPtER 10 179

Figure 10.6 Alignment of a section of genomic DnA from various species. This is a region of the gene for a DNA polymerase. Nucle- otides that differ from those in the human sequence are highlighted. The chance that any two of these sequences would randomly match is 1 in 1046.

Figure 10.7 A SnP-chip analysis. This SNP chip (inset), shown actual size, tests 550,000 SNPs. The small white box indicates the magnified por- tion shown. Each spot is a region where the individual’s genomic DNA has hybridized with one SNP sequence. A red or green dot means that the individual is homozy- gous for a SNP; a combined signal (yellow dot) indicates heterozygosity. (Inset) The Sanger Institute. Wellcome Images; (background) Wellcome Trust Sanger Institute.

its efforts. Then, in 2000, U.S. President Bill Clinton and British Prime Minister Tony Blair jointly declared that the sequence of the human genome could not be patented. Celera kept sequencing anyway, and, in 2001, the competing govern- mental and corporate teams published about 90 percent of the sequence. In 2003, fifty years after the discovery of the structure of DNA, the sequence of the human genome was officially completed.

Genomics It took 15 years to sequence the human genome for the first time, but the technology has improved so much that sequencing an entire genome now takes a few hours (Figure 10.5B). Anyone can now pay to have their genome sequenced. However, despite our ability to determine the sequence of an individual’s genome, it will be a long time before we understand all the information coded within that sequence. The human genome contains a massive amount of seemingly cryptic data. We can decipher some of this data by comparing genomes of different species, the premise being that all organisms are descended from shared ancestors, so all genomes are related to some extent. We see evidence of such genetic relationships simply by comparing the raw sequence data, which, in some regions of DNA, is extremely similar across many species (Figure 10.6).

The study of genomes is called genomics, a broad field that encompasses whole-genome comparisons, structural analysis of gene products, and surveys of small-scale variations in sequence. Genomics is providing powerful insights into evolution, and it has many medical benefits. We have learned the function of many human genes by studying their counterparts in other species. For instance, research- ers comparing human and mouse genomes discovered a human version of a mouse gene, APOA5, that encodes a lipoprotein. Mice with an APOA5 knockout have four times the normal level of triglycerides in their blood. The researchers then looked for—and found—a correlation between APOA5 mutations and high triglyceride levels in humans. High triglycerides are a risk factor for coronary artery disease.

DNA Profiling As you learned in Section 10.1, about 99 percent of the human genome sequence is identical in every member of the species. The differences you carry in your DNA make you unique. In fact, those differences are so unique that they can be used to identify you. Identifying an individual by his or her DNA is a method called DNA profiling. One DNA profiling method uses SNP-chips (an example is shown in Figure 10.1). A SNP-chip is a tiny glass plate with microscopic spots of DNA stamped on it. The DNA sample in each spot is a short, synthetic single strand with a unique SNP sequence. When an individual’s genomic DNA is washed over a SNP-chip, it hybridizes only with DNA spots that have a matching SNP sequence. Probes reveal where the genomic DNA has hybridized—and which of the SNPs are carried by the individual (Figure 10.7).

Another method of DNA profiling involves analysis of short tandem repeats in an individual’s chromosomes. Short tandem repeats usually occur in the same location in human chromosomes, but the number of times a sequence is repeated in each location differs among individuals. For example, one person’s DNA may have fifteen repeats of the nucleotides TTTTC at a certain spot on one chromosome. Another person’s DNA may have four repeats of this sequence in the same location. Short tandem repeats slip spontaneously into DNA during replication, and their numbers grow or shrink over generations. Unless two people are identical twins, the chance that they have identical short tandem repeats in even three regions of DNA is 1 in a quintillion (1018), which is far more than the number of people who have ever lived. Thus, an individual’s array of short tandem repeats is, for all practical purposes, unique.

Analyzing a person’s short tandem repeats begins with PCR, which is used to copy ten to thirteen particular regions of chromosomal DNA known to have

repeats. The lengths of the copied DNA fragments differ among most individuals, because the number of tandem repeats in those regions also differs. Thus, electro- phoresis can be used to reveal an individ- ual’s unique array of short tandem repeats (Figure 10.8).

Short tandem repeat analysis will soon be replaced by full genome sequencing, but for now it continues to be a common DNA profiling method. Geneticists com- pare short tandem repeats on Y chromosomes to determine relationships among male relatives, and to trace an individual’s ethnic heritage. They also track muta- tions that accumulate in populations over time by comparing DNA profiles of living humans with those of ancient ones. Such studies are allowing us to reconstruct population dispersals that happened in the ancient past.

Short tandem repeat profiles are routinely used to resolve kinship disputes, and as evidence in criminal cases. Within the context of a criminal or forensic investiga- tion, DNA profiling is called DNA fingerprinting. As of January 2014, the database

of DNA fingerprints maintained by the Federal Bureau of Investigation (the FBI) contained the short tandem repeat profiles of 10.7 million convicted offenders, and had been used in more than 200,000 criminal inves- tigations. DNA fingerprinting is also used to identify human remains, including the individuals who died in the World Trade Center on September 11, 2001.

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Take-Home Message 10.3 how do we use what researchers discover about DnA?

• improvements in DNA sequencing techniques allowed the human genome sequence to be determined. The technology has improved so much that an individual’s genome can now be sequenced in a few hours.

• Analysis of the human genome sequence is yielding new information about our genes and how they work.

• DNA profiling identifies individuals by the unique parts of their DNA.

genetic engineering Process by which deliberate changes are introduced into an individual’s genome.

genetically modified organism (GMO) Organ- ism whose genome has been modified by genetic engineering.

transgenic Refers to a genetically modified organism that carries a gene from a different species.

Figure 10.8 An individual’s (partial) short tandem repeat profile. Remember, human body cells are diploid. Double peaks appear on a profile when the two members of a chromo- some pair carry a different number of repeats.

Figure it Out: How many repeats does this individual have at the Penta D region?

Answer: 12 on one chromosome, and 14 on the other

B. The number of repeats is shown in a box below each peak. A peak’s location on the x-axis corresponds to the length of the DNA fragment amplified (a measure of the number of repeats). Peak size reflects amount of DNA.

A. Gray boxes indicate the regions of the individual’s DNA that were tested.

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BiOTEcHNOlOGy ChAPtER 10 181

Figure 10.9 Genetically modified bacteria. These E. coli bacteria are transgenic for a fluorescent jellyfish protein. The cells are genetically identical, so the visible variation in fluorescence among them reveals dif- ferences in gene expression. Such differences may help us discover why some bacteria of a population become dangerously resistant to antibiotics, and others do not. Courtesy of Systems Biodynamics Lab, P. I. Jeff Hasty, UCSD Department of Bioengineering, and Scott Cookson.

10.4 Genetic Engineering REMEMBER: carrots are orange because they contain the photosynthetic accessory pigment β-carotene (Section 5.2). The DNA sequence of a gene encodes an RNA or protein product; gene expression is the process by which information in a gene guides the assembly of an RNA or protein product (7.2).

Traditional cross-breeding methods can alter genomes, but only if individuals with the desired traits will interbreed. Genetic engineering takes gene-swapping to an entirely different level. Genetic engineering is a process by which an individual’s genome is deliberately modified. A gene from one species may be transferred to another to produce an organism that is transgenic, or a gene may be altered and reinserted into an individual of the same species. Both methods yield a genetically modified organism, or GMO.

Genetically Modified Microorganisms Most genetic engineering involves yeast and bacteria (Figure 10.9). Both types of cells have the metabolic machinery to make complex organic molecules, and they are easily engineered to produce, for example, medically important proteins. People with diabetes were among the first beneficiaries of such organisms. Insulin for their injections was once extracted from animals, but it provoked an allergic reaction in some people. Human insulin, which does not provoke allergic reactions, has been produced by transgenic E. coli since 1982. Slight modifications of the gene have yielded fast-acting and slow-release forms of human insulin.

Genetically engineered microorganisms also make proteins used in foods. For example, enzymes produced by modified microorganisms improve the taste and clarity of beer and fruit juice, slow bread staling, or modify certain fats. Cheese is traditionally made with an enzyme, chymosin, extracted from calf stomachs. Today, almost all cheese is made with calf chymosin produced by transgenic yeast.

Designer Plants As crop production expands to keep pace with human popula- tion growth, it places unavoidable pressure on ecosystems everywhere. Irrigation leaves mineral and salt residues in soils. Tilled soil erodes, taking topsoil with it. Runoff clogs rivers, and fertilizer in it causes algae to grow so fast that fish suffocate. Pesticides can be harmful to humans and other animals, including beneficial insects such as bees.

Pressured to produce more food at lower cost and with less damage to the envi- ronment, many farmers have begun to rely on genetically engineered crop plants. Genes can be introduced into plant cells by way of electric or chemical shocks, by blasting them with microscopic DNA-coated pellets, or by using Agrobacterium tumefaciens bacteria. A. tumefaciens carries a plasmid with genes that cause tumors to form on infected plants; hence the name Ti plasmid (for Tumor-inducing). Researchers replace the tumor-inducing genes with foreign or engineered genes, then use the plasmid as a vector to deliver the desired genes into plant cells. Whole plants can be grown from plant cells that integrate a recombinant plasmid into their chromosomes (Figure 10.10).

Many genetically modified crops carry genes that impart resistance to devastat- ing plant diseases and pests. GMO crops such as Bt corn and soy help farmers use smaller amounts of toxic pesticides. Organic farmers often spray their crops with spores of Bt (Bacillus thuringiensis), a bacterial species that makes a protein toxic only to some insect larvae. Researchers transferred the gene encoding the Bt protein

Figure 10.10 how to make a transgenic plant. (C) Pascal Goetgheluck/Science Source.

C. The infected plant cell divides, and its descendants form an embryo, then a plant. cells of the transgenic plant carry and express the foreign gene.

B. The bacterium infects a plant cell and transfers the Ti plasmid into it. The plasmid DNA, along with the foreign gene, becomes integrated into one of the cell’s chromosomes.

A. Ti plasmid carrying a foreign gene is inserted into an Agrobacterium tumefaciens bacterium.

A. tumefaciens bacterium

recombinant Ti plasmid

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into plants. The engineered plants produce the Bt protein, but otherwise they are essentially identical with unmodified plants. Larvae die shortly after eating their first and only GMO meal. Farmers can use much less pesticide on crops that make their own (Figure 10.11A).

Genetic modifications can make food plants more nutritious. For example, rice plants have been engineered to make β-carotene, an orange photosynthetic pigment that is remodeled by cells of the small intestine into vitamin A. These rice plants carry two genes in the β-carotene synthesis pathway: one from corn, the other from bacteria. One cup of their seeds—grains of Golden Rice—has enough β-carotene to satisfy a child’s daily need for vitamin A.

The USDA Animal and Plant Health Inspection Service (APHIS) regulates the introduction of GMOs into the environment. At this writing, APHIS has deregu- lated ninety-two crop plants, which means the plants are approved for unrestricted use in the United States. Worldwide, more than 330 million acres are currently planted in GMO crops, the majority of which are corn, sorghum, cotton, soy, canola, and alfalfa genetically engineered for resistance to the herbicide glyphosate. Rather than tilling the soil to control weeds, farmers can spray their fields with glyphosate, which kills the weeds but not the GMO crops.

Crops genetically engineered to resist glyphosate have been used in conjunction with the herbicide since the mid-1970s. Genes that confer glyphosate resistance are now appearing in weeds and other wild plants, as well as in unmodified crops— which means that recombinant DNA can (and does) escape into the environment. Glyphosate resistance genes are probably being transferred from transgenic plants to nontransgenic ones via pollen carried by wind or insects.

Biotech Barnyards Genetically modified animals can be produced by injecting DNA into a zygote, and then implanting the resulting embryo in a surrogate to com- plete its development. Genetically modified mice are invaluable in research (Fig- ure 10.11B). We have discovered the function of many human genes (including the APOA5 gene discussed in Section 10.3) by inactivating their counterparts in mice. Genetically modified mice are also used as models of human diseases. For example, researchers inactivated the molecules involved in the control of glucose metabolism, one by one. Studying the effects of the knockouts in mice has resulted in much of our current understanding of how diabetes works in humans.

Genetically engineered animals other than mice are also useful in research (Figure 10.11C), and some make molecules that have medical and industrial appli- cations. Various transgenic goats produce proteins used to treat cystic fibrosis, heart attacks, blood clotting disorders, and even nerve gas exposure. Milk from goats transgenic for lysozyme, an antibacterial protein in human milk, may protect infants and children in developing countries from acute diarrheal disease. Goats transgenic for a spider silk gene produce the silk protein in their milk; researchers can spin this protein into nanofibers that have medical and electronics applications. Rabbits make human interleukin-2, a protein that triggers immune cells to divide and is used as a cancer drug. We also engineer food animals. Genetic engineering has given us pigs with heart-healthy fat and environmentally friendly low-phosphate feces, muscle- bound trout, chickens that do not transmit bird flu, and cows that do not get mad cow disease, among other examples.

Many people think that genetically engineering livestock is unconscionable. Others see it as an extension of thousands of years of acceptable animal husbandry practices. The techniques have changed, but not the intent: We humans continue to have an interest in improving our livestock. Either way, tinkering with the genes of

A. The genetically modified plants that produced the corn on the left carry a gene from the bacteria Bacillus thuringi- ensis (Bt) that conferred insect resistance. compare the corn from unmodified plants, right. No pesticides were used on either crop.

B. Mice transgenic for multiple pigments (“brainbow mice”) are allowing researchers to map the complex neural circuitry of the brain. individual nerve cells in the brain stem of a brainbow mouse are visible in this fluorescence micrograph.

C. Zebrafish genetically modified to glow in places where BPA, an endocrine-disrupting chemical, is present. The fish are literally illuminating where this pollutant acts in the body—and helping researchers discover what it does when it gets there.

Figure 10.11 Some useful GMOs. (A) The Bt and Non-Bt corn photos were taken as part of field trial conducted on the main campus of Tennessee State University at the Institute of Agricultural and Environmental Research. The work was supported by a competitive grant from the CSREES, USDA titled Southern Agricultural Biotechnology Consortium for Underserved Communities, (2000–2005). Dr. Fisseha Tegegne and Dr. Ahmad Aziz served as Principal and Co-principal Investigators respectively to conduct the portion of the study in the State of Tennessee; (B) Courtesy of © Dr. Jean Levit. The Brainbow technique was developed in the laboratories of Jeff W. Lichtman and Joshua R. Sanes at Harvard University. This image has received the Bioscape imaging competition 2007 prize; (C) © Charles Taylor/University of Exeter.

BiOTEcHNOlOGy ChAPtER 10 183

animals raises a host of ethical dilemmas. Consider animals genetically engineered to carry mutations associated with human diseases—multiple sclerosis, cystic fibrosis, diabetes, cancer, or Huntington’s disease, for example. Researchers study these animals in order to understand the diseases, and to test potential treatments, without experimenting on humans. However, the modified animals often suffer the same terrible symptoms of the condition as humans do.

Some worry that our ability to tinker with genetics has surpassed our ability to understand the impact of the tinkering. Controversy raised by GMO use invites you to read the research and form your own opinions. The alternative is to be swayed by media hype (the term “Frankenfood,” for instance), or by reports from possibly biased sources (such as herbicide manufacturers).

Enhanced Spatial Learning Ability in Mice With an Autism Mutation

Autism is a neurobiological disorder with symptoms that include impaired social interactions and stereotyped patterns of behavior. Around 10 percent of autistic people also have an extraordinary skill or talent such as greatly enhanced memory. Mutations in the gene for neuroligin 3, an adhesion protein that connects brain cells to one another, have been associated with autism. One of these mutations is called R451C because the altered gene encodes a protein with an amino acid substitution: a cysteine (c) instead of an arginine (R) in position 451.

in 2007, Katsuhiko Tabuchi and his colleagues introduced the R451C mutation into the neuroligin 3 gene of mice. The researchers discovered that the genetically modified mice had impaired social behavior, and also that spacial learning ability was affected.

Spatial learning in mice is tested with a water maze, which consists of a small platform submerged a bit below the surface of a pool of water so it is invisible to swimming mice. Mice do not particularly enjoy swimming, so they try to locate the hidden platform as quickly as they can. When tested again, they remember the platform’s location by checking visual cues around the edge of the pool. How quickly they remember is a measure of their spatial learning ability. Figure 10.12 shows some of Tabuchi’s results.

Figure 10.12 Spatial learning ability in mice genetically modified to have a mutation associated with autism. Performance of genetically modified mice (R451C ) in a water maze was compared with that of unmodified (wild-type) mice.

Digging Into Data

a water maze

1. in the first test, how many days did unmodified mice need to learn to find the location of a hidden platform within 10 seconds?

2. Did the modified or the unmodified mice learn the location of the platform faster in the first test?

3. Which mice learned faster the second time around? 4. Which mice had the greatest improvement in memory?

Take-Home Message 10.4 What is genetic engineering?

• Genetic engineering is the directed alteration of an individual’s genome, and it results in a genetically modified organism (GMO).

• A transgenic organism carries a gene from a different species. Transgenic organisms, including bacteria and yeast, are used in research, medicine, and industry.

• Genetically modified crop plants can help farmers be more productive. However, widespread use of these crops is having unintended environmental effects.

• Genetic engineering creates animals that would be impossible to produce using tradi- tional cross-breeding methods.

Some worry that our ability to tinker with genetics has surpassed our ability to understand the impact of the tinkering.

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10.5 Modifying Humans REMEMBER: A gene that helps transform a normal cell into a tumor cell is an onco- gene; a proto-oncogene can become an oncogene (Section 8.3). An X-linked genetic disorder is associated with an allele on the X chromosome (9.7).

Gene Therapy We know of more than 15,000 serious genetic disorders. Collec- tively, they cause 20 to 30 percent of infant deaths each year, and account for half of all mentally impaired patients and a fourth of all hospital admissions. They also contribute to many age-related disorders, including cancer, Parkinson’s disease, and diabetes. Drugs and other treatments can minimize the symptoms of some genetic disorders, but gene therapy is the only cure. Gene therapy is the transfer of recombinant DNA into an individual’s body cells, with the intent to correct a genetic disorder or treat a disease. Typically, the transfer inserts an unmutated gene into the individual’s chromosomes.

DNA can be introduced into human cells in many ways, for example by direct injection, electrical pulses, lipid clusters, nanoparticles, or genetically engineered viruses. Viruses have molecular machinery that delivers their genomes into cells they infect. Those used as vectors have DNA that splices itself into the infected cells’ chromosomes, along with foreign DNA that has been inserted into it.

Human gene therapy is a compelling reason to embrace genetic engineer- ing research. It is now being tested as a treatment for AIDS, muscular dystrophy, heart attack, sickle-cell anemia, cystic fibrosis, hemophilia A, Parkinson’s disease, Alzheimer’s disease, several types of cancer, and inherited diseases of the eye, the ear, and the immune system.

People have already benefited from gene therapy. Consider SCID-X1, a severe X-linked genetic disorder that stems from a mutated allele of the IL2RG gene. The gene encodes a receptor for an immune signaling molecule. Without treat- ment, people affected by this disorder can survive only in germ-free isolation tents because they cannot fight infections (a diminished life in a sterile isolation tent was the source of the term “bubble boy”). In the late 1990s, researchers used a geneti- cally engineered virus to insert unmutated copies of IL2RG into cells taken from the bone marrow of twenty boys with SCID-X1. Each child’s modified cells were infused back into his bone marrow. Within months of their treatment, eighteen of the boys left their isolation tents (Figure 10.13A). Gene therapy had repaired their immune systems.

Gene therapy is now being tested as a treatment for acute lymphocytic leuke- mia, a typically fatal cancer of bone marrow cells. A viral vector is used to insert a gene into immune cells extracted from patients. When the resulting genetically modified cells are reintroduced into the patients’ bodies, the inserted gene directs the destruction of cancer cells (Figure 10.13B). The therapy seems to work astonish- ingly well: In one patient, all traces of the leukemia vanished in eight days.

Despite the successes, manipulating a gene within the context of a living individual is unpredictable even when we know its sequence and location on a chromosome. No one, for example, can predict with absolute certainty where a virus-injected gene will become integrated into a chromosome. Its insertion might disrupt other genes. If it interrupts a gene that is part of the controls over cell divi- sion, then cancer might be the outcome. Consider that five of the twenty boys first treated with gene therapy for SCID-X1 developed leukemia, and one of them died. Developers of the gene therapy had wrongly predicted that cancer related to it would be rare. Research now implicates the very gene targeted for repair, especially

Figure 10.13 Gene therapy: success stories. (A) © Huw Evans Agency, Cardiff; (B) © Kari Whitehead Photography.

A. Rhys Evans, shown here at age 10, was born with SciD-X1. His immune system has been permanently repaired by gene therapy.

B. Six-year-old Emily Whitehead was just days from death when she underwent an experimental gene therapy for acute lympho- cytic leukemia. Two years later, she remains cancer-free.

BiOTEcHNOlOGy ChAPtER 10 185

when combined with the virus that delivered it. The viral DNA preferentially inserted itself into the children’s chromosomes at a site near a proto-oncogene. The insertion activated the gene by triggering its transcription, and that is how the leu- kemia began. Since that time, researchers have used PCR to detect viral integration sites and improve the design of the vector. The development of more efficient and specific viral vectors has reduced the risk associated with all types of gene therapy.

Eugenics Eliminating undesirable human traits is part of eugenics, the philoso- phy of deliberately improving the genetic qualities of the human race. Eugenics has been used as a justification for some of the most horrific episodes in human history, including the genocide of 6 million Jews during World War II; thus, it continues to be a hotly debated social issue. For example, using gene therapy to cure genetic disorders seems like an acceptable goal to most people, but imagine taking this idea a bit further. Would it also be acceptable to engineer the genome of an individual who is within a normal range of phenotype in order to modify a particular trait? Researchers have already produced mice that have improved memory, enhanced learning ability, bigger muscles, and longer lives. Why not people?

Given the pace of genetics research, the debate is no longer about how we would engineer desirable traits, but how we would choose the traits that are desir- able. Realistically, cures for many severe but rare genetic disorders will not be found, because the financial return would not cover the cost of the research. Eugenics, however, may be profitable. How much would potential parents pay to be sure that their child will be tall or blue-eyed, with breathtaking strength or intelligence? What about a treatment that can help you lose that extra weight, and keep it off permanently? The gray area between interesting and abhorrent can be very different depending on who is asked. In a survey conducted in the United States, more than 40 percent of those interviewed said they would be fine with using gene therapy to make smarter and cuter babies. In one poll of British parents, 10 percent would use it to keep a child from growing up to be homosexual, and 18 percent would be will- ing to use it to keep a child from being aggressive.

Some people are concerned that gene therapy puts us on a slippery slope that may result in irreversible damage to ourselves and to the biosphere. We as a soci- ety may not have the wisdom to know how to stop once we set foot on that slope; one is reminded of our peculiar human tendency to leap before we look. And yet, something about the human experience allows us to dream of such things as wings of our own making, a capacity that carried us into space. In this brave new world, the questions before you are these: What do we stand to lose if serious risks are not taken? And, do we have the right to impose the potential consequences on people who would choose not to take those risks?

Take-Home Message 10.5 Can people be genetically modified?

• Genes can be transferred into a person’s cells to correct a genetic disorder or treat a disease. However, the outcome of altering a person’s genome remains unpredictable given our current understanding of how the genome works.

• We as a society continue to work our way through the ethical implications of applying DNA technologies.

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gene therapy Treating a genetic defect or disorder by transferring a normal or modified gene into the affected individual.

The debate is no longer about how we would engineer desirable traits, but how we would choose the traits that are desirable.

186

Summary to help farmers produce food more efficiently. Some crops are genetically modified to have enhanced nutritional value.

Section 10.5 With gene therapy, a gene is transferred into body cells to correct a genetic defect or treat a disease. Potential benefits of genetically modifying humans must be weighed against potential risks. the practice raises ethical issues such as whether

eugenics would be desirable in some circumstances.

Section 10.1 Personal genetic testing, which reveals a person’s unique array of single-nucleotide polymorphisms, or SNPs, is beginning to revolutionize the way medicine is practiced.

Section 10.2 in DNA cloning, researchers use restriction enzymes to cut a sample of DnA into fragments, and then use DnA ligase to splice the fragments into plasmids or other cloning vectors. the resulting molecules of recombinant DNA are

inserted into host cells such as bacteria. Division of host cells produces huge populations of genetically identical descendant cells (clones), each with a copy of the cloned DnA fragment.

A DNA library is a collection of cells that contain different fragments of DnA, often representing an organism’s entire genome. Researchers can use probes to identify cells that carry a specific fragment of DnA. the polymerase chain reaction (PCR) uses primers and a heat-resistant DnA polymerase to rapidly increase the number of copies of a targeted section of DnA.

Section 10.3 Advances in sequencing, which reveals the order of nucleotides in DnA, allowed the DnA sequence of the entire human genome to be determined. DnA polymerase is used to partially replicate a DnA template. the reaction produces a

mixture of DnA fragments of all different lengths; electrophoresis separates the fragments by length into bands.

Genomics gives us insights into the function of the human genome. Similarities between genomes of different organisms are evidence of evolutionary relationships, and can be used as a predictive tool in research. DNA profiling identifies a person by the unique parts of his or her DnA. An example is the determination of an individual’s unique array of SnPs or short tandem repeats. Within the context of a criminal investigation, a DnA profile is called a DnA fingerprint.

Section 10.4 Recombinant DnA technology is the basis of genetic engineering, the directed modification of an organism’s genetic makeup with the intent to modify its phenotype. A gene from one species is inserted into an individual of a different species to make a

transgenic organism, or a gene is modified and reinserted into an individual of the same species. the result of either process is a genetically modified organism (GMO).

Bacteria and yeast, the most common genetically engineered organisms, produce proteins that have medical value. the majority of the animals that are being created by genetic engineering are used for medical applications or research. Most transgenic crop plants, which are now in widespread use worldwide, were created

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1. cut(s) DnA molecules at specific sites. a. DnA polymerase c. Restriction enzymes b. DnA probes d. DnA ligase

2. A is a molecule that can be used to carry a fragment of DnA into a host organism. a. cloning vector c. gMo b. chromosome d. cDnA

3. For each species, all in the complete set of chromosomes is/are the . a. genomes; genotype c. SnPs; genome b. DnA; genome d. transgenics; gMos

4. A set of cells that host various DnA fragments collectively representing an organism’s entire set of genetic information is called a . a. genome d. gMo b. DnA library e. single-nucleotide c. clone polymorphism

5. PcR can be used . a. to increase the number of specific DnA fragments b. in DnA profiling c. to modify a human genome d. as a cloning vector e. a and b are correct f. all of the above

6. Fragments of DnA can be separated by electrophoresis according to . a. sequence c. species b. length d. SnPs

Self-Quiz

BiOTEcHNOlOGy ChAPtER 10 187

1. Restriction enzymes in bacterial cytoplasm cut injected bacte- riophage DnA wherever certain sequences occur. Why do you think these enzymes do not chop up the bacterial chromosome, which is exposed to the enzymes in cytoplasm?

2. in 1918, an influenza pandemic that originated with avian flu killed 50 million people. Researchers isolated samples of that virus from bodies of infected people preserved in Alaskan per- mafrost since 1918. From the samples, they sequenced the viral genome, then reconstructed the virus. the reconstructed virus is 39,000 times more infectious than modern influenza strains, and 100 percent lethal in mice.

Understanding how this virus works can help us defend ourselves against other strains that may arise. For example, discovering what makes it so infectious and deadly would help us design more effective vaccines. critics of the research are concerned: if the virus escapes the containment facilities (even though it has not done so yet), it might cause another pandemic. Worse, the published DnA sequence and methods to make the virus could be used for criminal purposes. Do you think this research makes us more or less safe?

7. Taq polymerase is used for PcR because it . a. tolerates the high temperature needed to separate DnA

strands b. is an enzyme from a bacterium c. does not require primers d. is genetically modified

8. is a technique to determine the order of nucleotides in a fragment of DnA. a. PcR c. electrophoresis b. Sequencing d. nucleic acid hybridization

9. Which of the following can be used to carry foreign DnA into host cells? choose all of the correct answers. a. RnA e. lipid clusters b. viruses f. blasts of microscopic pellets c. PcR g. a DnA library d. plasmids h. sequencing

10. Put the following tasks in the order they would occur during a cloning experiment. a. using DnA ligase to seal DnA fragments into vectors b. using a probe to identify a clone in the library c. using DnA polymerase to sequence the DnA of the clone d. making a DnA library of clones e. cutting genomic DnA with restriction enzymes

11. A transgenic organism . a. carries a gene from another species b. has been genetically modified c. both a and b

12. true or false? A transgenic organism can pass its foreign gene to offspring.

13. can correct a genetic defect in an individual. a. cloning vectors c. Xenotransplantation b. gene therapy d. a and b

14. true or false? Some humans are genetically modified.

15. Match the terms with the best description. DnA profile a. gMo with a foreign gene ti plasmid b. alleles commonly have them eugenics c. a person’s unique collection SnP of short tandem repeats transgenic d. selecting “desirable” traits gMo e. genetically modified f. used in plant gene transfers

table 10.1 Paternity test Results

Marker DnA Samples tested

Mother Baby Alleged Father #1 Alleged

Father #2

cSF1PO 15, 17 17, 23 23, 27 17, 15

FGA 9, 9 9, 9 9, 12 9, 12

THO1 29, 29 29, 27 27, 28 29, 28

TPOX 14, 18 18, 20 15, 20 17, 22

VWA 14, 14 14, 14 14, 14 14, 16

D3S1358 11, 14 14, 16 12, 16 14, 20

D5S818 11, 13 10, 13 8, 10 18, 18

D7S820 7, 13 13, 13 13, 19 13, 13

D8S1179 13, 13 13, 15 12, 15 10, 12

D13S317 12, 12 10, 12 8, 10 12, 17

D16S539 12, 14 14, 12 14, 14 18, 25

D18S51 5, 6 6, 22 22, 6 5, 22

D21S11 15, 17 17, 22 15, 22 22, 22

Table 10.1 shows the results of a paternity test using short tandem repeats. Who’s the daddy? How sure are you?

critical thinking

Visual Question

11.1 Reflections of a Distant Past 190

11.2 Confusing Discoveries 191

11.3 A Flurry of New Ideas 192

11.4 Fossil Evidence 196

11.5 Drifting Continents 200

11.6 Evidence in Form 204

11.7 Evidence in Function 206

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11.1 Reflections of a Distant Past How do you think about time? Perhaps you can conceive of a few hundred years of human events, maybe a few thousand, but how about a few million? Envisioning the very distant past requires an intellectual leap from the familiar to the unknown. One way to make that leap involves, surprisingly, asteroids. Asteroids are small planets hurtling through space. They range in size from 1 to 1,500 kilometers (roughly 0.5 to 1,000 miles) across. Millions of them orbit the sun between Mars and Jupi- ter—cold, stony leftovers from the formation of our solar system. Asteroids do not emit light, so they are difficult to see even with the best telescopes. Thus, asteroids can pass very close to Earth undetected, and many are discovered as they do. Some have not passed us by at all.

Consider the mile-wide Barringer Crater in Arizona (Figure 11.1A). An asteroid 45 meters (150 feet) wide made this impressive pockmark in the desert sandstone when it slammed into Earth 50,000 years ago, its impact 150 times more powerful than the bomb that leveled Hiroshima. No humans were in North Amer- ica at the time of the impact. If there were no witnesses, how is it possible to know anything about what happened? We often reconstruct history by studying physical evidence of past events. Geologists were able to infer the most probable cause of the Barringer Crater by analyzing tons of meteorites, melted sand, and other rocky clues at the site.

Similar evidence points to even larger impacts in the more distant past. For example, fossil hunters have long known about a mass extinction, or permanent loss of major groups of organisms, that occurred 66 million years ago. The event is marked by an unusual, worldwide formation of sedimentary rock (Figure 11.1B) called the K–Pg boundary sequence (it was formerly known as the K–T bound-

ary). There are plenty of dinosaur fossils below this formation. Above it, in layers of rock that were deposited more recently, there are no dinosaur fossils, anywhere. The formation consists of an unusual clay that is rich in iridium, an element rare on Earth’s surface but common in asteroids. It also contains shocked quartz (left) and small glass spheres called tektites— rocks that form when quartz or sand (respectively) undergoes a sudden, violent application of extreme pressure. The only

processes on Earth known to produce these minerals are nuclear explosions and asteroid impacts.

Geologists concluded that the K–Pg boundary layer must have originated with extraterrestrial material, and began looking for evidence of an asteroid that hit Earth 66 million years ago—one big enough to cover the entire planet with its debris. Twenty years later, they found it: an impact crater the size of Ireland off the coast of the Yucatán Peninsula. To make a crater this big, an asteroid 20 km (12 miles) wide would have slammed into Earth with a force 40 million times more powerful than the one that made the Barringer Crater—enough to cause an ecological disaster of sufficient scale to wipe out almost all life on Earth.

You are about to make an intellectual leap through time, to places that were not even known a few centuries ago. We invite you to launch yourself from this premise: Natural phenomena that occurred in the past can be explained by the same physical, chemical, and biological processes that operate today. That premise is the founda- tion for scientific research into the history of life. The research represents a shift from experience to inference—from the known to what can only be surmised—and it gives us astonishing glimpses into the distant past.

Figure 11.1 From evidence to inference. (A) © Brad Snowder; (B) © David A. Kring, NASA/Univ. Arizona Space Imagery Center; inset, © U.S. Geological Survey.

A. What made the Barringer Crater? Rocky evidence points to a 300,000-ton asteroid that collided with Earth 50,000 years ago.

B. the K–Pg boundary sequence is an unusual, world- wide formation of sedimentary rock that formed 66 mil- lion years ago. this rock formation marks an abrupt transition in the fossil record that implies a mass extinc- tion of the dinosaurs. It also contains materials consis- tent with an asteroid impact. the impact of an asteroid big enough to blanket the Earth with its debris would have had catastrophic aftereffects on life at the time. the red pocketknife gives an idea of scale.

Application

K–Pg boundary sequence

EvIDENCE oF EvolutIoN ChAPter 11 191

11.2 Confusing Discoveries reMeMBer: Naming species in a consistent way became a priority in the 18th cen- tury (section 1.4). scientific discoveries may provoke controversy when a society’s moral standards are interwoven with its understanding of nature (1.6).

About 2,300 years ago, the Greek philosopher Aristotle described nature as a con- tinuum of organization, from lifeless matter through complex plants and animals. Aristotle’s work greatly influenced later European thinkers, who adopted his view of nature and modified it in light of their own beliefs. By the fourteenth century, Europeans generally believed that a “great chain of being” extended from the lowest form of life (plants), up through animals, humans, and spiritual beings. Each link in the chain was a species, and each was said to have been forged at the same time, in one place, and in a perfect state. The chain was complete. Because everything that needed to exist already did, there was no room for change.

In the 1800s, European naturalists embarked on globe-spanning survey expeditions and brought back tens of thousands of plants and animals from Asia, Africa, North and South America, and the Pacific Islands. Each newly discovered species was carefully catalogued as another link in the chain of being. The explorers began to see patterns in where species live and similarities in body plans, and had started to think about natural forces that shape life. These explorers were pioneers in biogeography, the study of patterns in the geographic distribution of species and communities. Some of the patterns raised questions that could not be answered within the framework of prevailing belief systems. For example, globe-trotting explorers had discovered plants and animals living in extremely isolated places. The isolated species looked suspiciously similar to species living on the other side of impassable mountain ranges, or across vast expanses of open ocean. Consider the emu, rhea, and ostrich, three types of bird native to three different continents. These birds share a set of unusual features (Figure 11.2). Alfred Wallace, an explorer partic- ularly interested in the geographical distribution of animals, thought that the shared traits might mean that the birds descended from a common ancestor (and he was correct), but he had no idea how they could have ended up on different continents.

Naturalists of the time also had trouble classifying organisms that are very similar in some features, but different in others. For example, both plants shown in Figure 11.3 live in hot deserts where water is seasonally scarce. Both have rows of sharp spines that deter herbivores, and both store water in their thick, fleshy stems.

biogeography study of patterns in the geographic distribution of species and communities.

Figure 11.2 Similar-looking, related species native to distant geographic realms. these birds are unlike most others in several unusual features, including long, muscular legs and an inability to fly. All are native to open grassland regions about the same distance from the equator. (A) Rebecca Yale/Getty Images; (B) © Nico Stengert/Novarc Images/Alamy; (C) © Earl & Nazima Kowall/Corbis.

C. Emu, native to Australia.B. Rhea, native to south America.A. ostrich, native to Africa.

Figure 11.3 Similar-looking, unrelated species. on the left, saguaro cactus (Carnegiea gigantea), native to the sonoran Desert of Arizona. on the right, an African milk barrel cactus (Euphorbia horrida), native to the Great Karoo desert of south Africa. Left, © Marka/SuperStock; right, © Richard J. Hodgkiss, www.succulent-plant.com.

192 Unit 3 EvolutIoN AND DIvERsIty

However, their reproductive parts are very different, so these plants cannot be (and are not) as closely related as their outward appearance might suggest.

Observations such as these are examples of comparative morphology, the study of anatomical patterns: similarities and differences among the body plans of organisms. Today, comparative morphology is only one branch of taxonomy, but in the nineteenth century it was the only way to distinguish species. In some cases, comparative morphology revealed anatomical details (body parts with no apparent function, for example) that added to the mounting confusion. If every species had been created in a perfect state, then why were there useless parts such as wings in birds that do not fly, eyes in moles that are blind, or remnants of a tail in humans (Figure 11.4)?

Fossils were puzzling too. A fossil is physical evidence—remains or traces—of an organism that lived in the ancient past. Geologists mapping rock formations exposed by erosion or quarrying had discovered identical sequences of rock layers in different parts of the world. Deeper layers held fossils of simple marine life. Lay- ers above those held similar but more complex fossils (Figure 11.5). In higher layers, fossils that were similar but even more complex resembled modern species. What did these sequences mean? Fossils of many animals unlike any living ones were also being unearthed. If these animals had been perfect at the time of creation, then why had they become extinct?

Taken as a whole, the accumulating discoveries from biogeography, compara- tive morphology, and geology did not fit with prevailing beliefs of the nineteenth century. If species had not been created in a perfect state (and extinct species, fossil sequences, and “useless” body parts implied that they had not), then perhaps species had indeed changed over time.

11.3 A Flurry of New Ideas reMeMBer: Epigenetic modifications of DNA that alter gene expression may persist for generations (section 7.7). Paired genes on homologous chromosomes may vary as alleles; alleles are the basis of differences in traits shared by a species (8.4). the environment influences gene expression, and therefore affects phenotype (9.5).

Squeezing New Evidence Into Old Beliefs In the nineteenth century, naturalists were faced with increasing evidence that life on Earth, and even Earth itself, had changed over time. Around 1800, Georges Cuvier (left), an expert in zoology and paleontology, was trying to make sense of the new information. He knew that many fossil species seemed to have no living counterparts. Given this evidence, he proposed an idea

Take-Home Message 11.2 Why did observations of nature change our thinking in the nineteenth century?

• Increasingly extensive observations of nature in the nineteenth century did not fit with prevailing belief systems.

• Cumulative findings from biogeography, comparative morphology, and geology led naturalists to question traditional ways of interpreting the natural world.

Figure 11.4 A vestigial structure: human tailbones. Nineteenth-century naturalists were well aware of—but had trouble explaining—body structures such as human tailbones that had apparently lost most or all function. © Zephyr/Science Photo Library/Science Source.

Figure 11.5 Sequence of ten fossil foraminifera. Courtesy of Daniel C. Kelley, Anthony J. Arnold, and William C. Parker, Florida State University Department of Geological Science.

coccyx (tailbones)

Foraminifera are single- celled protists; most of the 4,000 known species alive today are found at the bottom of the ocean. All secrete a durable shell of calcium carbonate. After the organism dies, the shell may become fossilized as sediments accumulate on top of it.

Researchers found these representative shells of ancient foraminifera in cylindrical sections (core samples) of the ocean floor, each in a successive layer of stacked rock.

58 million years old

64.5 million years old

EvIDENCE oF EvolutIoN ChAPter 11 193

startling for the time: Many species that had once existed were now extinct. Cuvier also knew about evidence that Earth’s surface had changed. For example, he had seen fossilized seashells in rocks at the tops of mountains far from modern seas. Like most others of his time, he assumed Earth’s age to be in the thousands, not billions, of years. He reasoned that geologic forces unlike any known at the time would have been necessary to raise seafloors to mountaintops in such a short time span. These catastrophic geological events would have caused extinctions, after which surviving species repopulated the planet. Cuvier’s idea came to be known as catastrophism. We now know that catastrophism is incorrect; geologic processes have not changed over time.

Another naturalist, Jean-Baptiste Lamarck, was thinking about processes that might drive evolution, or change in a line of descent. A line of descent is also called

a lineage. Lamarck (left) thought that a species gradually improved over generations because of an inherent drive toward perfection, up the chain of being. The drive directed an unknown “fluida” into body parts needing change. By Lamarck’s hypothesis, environmental pressures cause an internal requirement for change in an individual’s

body, and the resulting change is inherited by offspring. Imagine using Lamarck’s hypothesis to explain why a giraffe’s neck is very long. You might predict that some short-necked ancestor of the modern giraffe stretched its neck to browse on leaves beyond the reach of other animals. The stretches may have even made its neck a bit longer. By Lamarck’s hypothesis, the animal’s offspring would inherit a longer neck. The modern giraffe would have been the result of many generations that strained to reach ever loftier leaves. Lamarck was correct in thinking that environmental factors affect traits, but his understanding of how inheritance works was incomplete.

Darwin and the HMS Beagle Lamarck’s ideas about evolution influenced the thinking of Charles Darwin, who, at the age of 22, joined a survey expedition to South America on a ship called Beagle. Since he was eight years old, Darwin had wanted to hunt, fish, collect shells, or watch insects and birds—anything but sit in school. After a failed attempt to study medicine in college, he earned a degree in theology from Cambridge. During his studies, Darwin had spent most of his time with faculty members and other students who embraced natural history.

The Beagle set sail for South America in December 1831 (Figure 11.6). The young man who had hated school and had no formal training in science quickly became an enthusiastic naturalist. During the Beagle’s five-year voyage, Darwin found many unusual fossils, and saw diverse species living in environments that ranged from the sandy shores of remote islands to plains high in the Andes. Along

comparative morphology the scientific study of similarities and differences in body plans.

evolution Change in a line of descent.

fossil Physical evidence of an organism that lived in the ancient past.

lineage line of descent.

Figure 11.6 Charles Darwin and the Beagle. With Darwin (left) aboard as ship’s naturalist, the Beagle (middle) originally set sail to map the coast of south America, but ended up circumnavigating the globe. Right, the path of the voyage is shown from red to blue.

Darwin’s detailed observations of the geology, fossils, plants, and animals he encountered on this expedition changed the way he thought about evolution. Left, painting by George Richmond; middle, © Gordon Chancellor.

0 5000(km)

0 3000(mi)

Plymouth

Azores Tenerife

Cape Verde

Bahia

Rio de Janeiro

Montevideo

Falkland Islands

Valparaiso

Callao Lima

Galapagos

Sydney

Hobart

King George's Sound

Cocos (Keeling) Isl.

Mauritius

Cape Town

Accumulating discoveries in the nineteenth century did not fit with prevailing beliefs.

194 Unit 3 EvolutIoN AND DIvERsIty

the way, he read the first volume of a new and popular book, Charles Lyell’s Principles of Geology. Lyell (left) was a proponent of what became known as the theory of uniformity, the idea that gradual, repetitive change had shaped Earth. For many years, geologists had been chipping away at the sandstones, limestones, and other types of rocks that form

from accumulated sediments at the bottom of lakes, rivers, and oceans. These rocks held evidence that the gradual processes of geologic change operating in the present were the same ones that operated in the distant past.

By the theory of uniformity, strange catastrophes were not necessary to explain Earth’s surface. Gradual, everyday geologic processes such as erosion by wind and water could have sculpted Earth’s current landscape over great spans of time. This theory challenged the prevailing belief that Earth was 6,000 years old. According to traditional scholars, people had recorded everything that happened in those 6,000 years—and in all that time, no one had mentioned seeing a species evolve. However, by Lyell’s calculations, it must have taken millions of years to sculpt Earth’s surface. Darwin’s exposure to Lyell’s ideas gave him insights into the geologic history of the regions he would encounter on his journey. Was millions of years enough time for species to evolve? Darwin thought that it was.

A Key Insight—Variation in Traits Among the thousands of specimens Darwin collected on his voyage and sent to England were fossil glyptodons from Argen- tina. These armored mammals are extinct, but they have many traits in common with modern armadillos. Like glyptodons, armadillos have helmets and protective shells that consist of unusual bony plates (Figure 11.7). Armadillos also live only in places where glyptodons once lived. Could the shared traits and distribution mean that glyptodons were ancient relatives of armadillos? If so, perhaps traits of their common ancestor had changed in the line of descent that led to armadillos. But why would such changes have occurred?

After Darwin returned to England, he pondered his notes and fossils, and read an essay by one of his contemporaries, economist Thomas Malthus. Malthus (left) had correlated increases in the size of human populations with episodes of famine, disease, and war. He proposed the idea that humans run out of food, living space, and other resources because they tend to reproduce beyond the capacity of their environment to sustain

them. When that happens, the individuals of a population must either compete with one another for the limited resources, or develop new technologies to increase productivity. Darwin realized that Malthus’s ideas had wider application: All popu- lations, not just human ones, must have the capacity to produce more individuals than their environment can support.

Reflecting on his journey, Darwin started thinking about how individuals of a species often vary a bit in the details of shared traits such as size, coloration, and so on. He saw such variation among finch species on isolated islands of the Galápagos archipelago. This island chain is separated from South America by 900 kilometers (550 miles) of open ocean, so most species living on the islands did not have the opportunity for interbreeding with mainland populations. The Galápagos island birds resembled finch species in South America, but many had unique traits that suited their particular island habitat.

Darwin was familiar with dramatic variations in traits that selective breeding could produce in pigeons, dogs, and horses. He recognized that a natural environ- ment could similarly select traits that make individuals of a population suited to it. It dawned on Darwin that having a particular form of a shared trait might give an

Figure 11.7 Ancient relatives: armadillo and glyptodon. Even though these animals are widely separated in time, they share a restricted distribution and unusual traits, including a shell and helmet of keratin-covered bony plates—a material similar to crocodile and lizard skin. (the fossil in B is missing its helmet.) their similarities were a clue that helped Darwin develop the theory of evolution by natural selection. (A) © John White; (B) 2004 Arent.

A. A modern armadillo, about a foot long.

B. Fossil of a glyp todon, an automobile-sized mammal that existed from 2 million to 15,000 years ago.

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EvIDENCE oF EvolutIoN ChAPter 11 195

individual an advantage over competing members of its species. In any population, some individuals have forms of shared traits that make them better suited to their environment than others. In other words, individuals of a natural population vary in fitness. Today, we define fitness as the degree of adaptation to a specific environ- ment, and measure it by relative genetic contribution to future generations. A form of a heritable trait that enhances an individual’s fitness is called an adaptive trait, or evolutionary adaptation.

Over many generations, individuals that have adaptive traits tend to sur- vive longer and reproduce more than their less fit rivals. Darwin understood that this process, which he called natural selection, could be a mechanism by which evolution occurs. If an individual has a form of a trait that makes it better suited to an environment, then it is better able to survive. If an individual is better able to survive, then it has a better chance of living long enough to produce offspring. If individuals with an adaptive form of a trait produce more offspring than those that do not, then the frequency of that form will tend to increase in the population over successive generations. Table 11.1 summarizes this reasoning in modern terms.

Great Minds Think Alike Darwin wrote out his ideas about natural selection, but let ten years pass without publishing them. In the meantime, Alfred Wallace (left), who had been studying wildlife in the Amazon basin and the Malay Archipelago, wrote an essay and sent it to Darwin for advice. Wallace’s essay outlined evolution by natural selection—the very same theory as Darwin’s. Wallace had written earlier letters to Darwin and

Lyell about patterns in the geographic distribution of species, and had come to the same conclusion.

In 1858, just weeks after Darwin received Wallace’s essay, the theory of evolu- tion by natural selection was presented at a scientific meeting. Both Darwin and Wallace were credited as authors. Wallace was still in the field and knew nothing about the meeting, which Darwin did not attend. The next year, Darwin published On the Origin of Species, which laid out detailed evidence in support of the theory. Many people had already accepted the idea of descent with modification (evolu- tion). However, there was a fierce debate over the idea that natural selection drives evolution. Decades would pass before experimental evidence from the field of genetics led to its widespread acceptance as a theory by the scientific community. As you will see in the remainder of this unit, the theory of evolution by natural selection is supported by and helps explain the fossil record as well as similarities and differences in the form, function, and biochemistry of living things.

Take-Home Message 11.3 how did new evidence change the way people in the 19th century thought about the history of life?

• Evidence found in the 1800s led to the idea that Earth and the species on it had changed over very long spans of time. this idea set the stage for Darwin’s theory of evolution by natural selection.

• Natural selection is a process that drives evolutionary change: Individuals of a popula- tion survive and reproduce with differing success depending on the details of their shared, heritable traits.

• Adaptive traits enhance fitness.

Observations about populations • Natural populations have an inherent capacity to

increase in size over time.

• As a population expands, resources that are used by its individuals (such as food and living space) eventually become limited.

• When resources are limited, the individuals of a population compete for them.

Observations about genetics • Individuals of a species share certain traits.

• Individuals of a natural population vary in the details of those shared traits.

• shared traits have a heritable basis, in genes. slightly different forms of those genes (alleles) give rise to variation in shared traits.

inferences • A certain form of a shared trait may make its

bearer better able to survive.

• Individuals of a population that are better able to survive tend to leave more offspring.

• thus, an allele associated with an adaptive trait tends to become more common in a population over time.

adaptive trait (adaptation) A form of a heritable trait that enhances an individual’s fitness.

fitness Degree of adaptation to an environment, as measured by an individual’s relative genetic contribu- tion to future generations.

natural selection Differential survival and reproduc- tion of individuals of a population based on differ- ences in shared, heritable traits.

table 11.1 Principles of natural Selection

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196 Unit 3 EvolutIoN AND DIvERsIty

11.4 Fossil Evidence reMeMBer: Atoms of a radioisotope have an unstable nucleus that breaks up spontaneously, emitting radiation in a process called radioactive decay (section 2.2). Molecular oxygen had been a very small component of Earth’s atmosphere before photosynthesis evolved (5.5).

Even before Darwin’s time, fossils were recognized as stone-hard evidence of earlier forms of life. Most fossils consist of mineralized bones, teeth, shells, seeds, spores, or other durable body parts (Figure 11.8). Trace fossils such as footprints and other body impressions, nests, burrows, trails, eggshells, or feces, are evidence of an ancient organism’s activities.

The process of fossilization typically begins when an organism or its traces become covered by sediments, mud, or ash. Groundwater then seeps into the remains, filling spaces around and inside of them. Minerals dissolved in the water gradually replace minerals in bones and other hard tissues. Mineral particles that settle out of the groundwater and crystallize inside cavities and impressions form detailed imprints of internal and external structures. Sediments that slowly accumu- late on top of the site exert increasing pressure, and, after a very long time, extreme pressure transforms the mineralized remains into rock.

Most fossils are found in layers of sedimentary rock (Figure 11.9). Sedimentary rocks form as rivers wash silt, sand, volcanic ash, and other materials from land to sea. Mineral particles in the materials settle on seafloors in horizontal layers that often vary in thickness and composition. After hundreds of millions of years, the layers of sediments become compacted into layers of rock. Even though most sedi- mentary rock forms at the bottom of a sea, geologic processes can tilt the rock and lift it far above sea level, where the layers may become exposed by the erosive forces of water and wind.

Biologists study sedimentary rock formations in order to understand the his- torical context of ancient life. Usually, the deepest layers in a particular formation of rock were the first to form, and those closest to the surface formed most recently. Thus, in general, the deeper the layer, the older the fossils it contains. Features of the formations can provide information about local and global events that were occur-

ring as they formed. Consider banded iron, a unique forma- tion named after its distinctive striped appearance (left). Huge deposits of this sedimentary rock are the source of most iron we mine for steel today, but they also hold a record of how the evolution of photosynthesis changed the chemistry of Earth.

Banded iron started forming about 2.4 billion years ago, right after photosynthesis evolved. At that time, Earth’s atmosphere and ocean contained very little oxygen, and ocean water contained a lot of dissolved iron. Oxygen released into the ocean by early photosynthetic bacteria quickly combined with the dissolved iron. The resulting iron compounds are completely insoluble in water, and they began to rain down on the ocean floor in massive quantities, forming layers of sediment that compacted into banded iron formations. This process continued for about 600 million years, until ocean water no longer contained very much dissolved iron.

The Fossil Record We have fossils for more than 250,000 known species. Considering the current range of biodiversity, there must have been many millions more, but we will never know all of them. Why not? The odds are against finding evidence of an extinct species, because fossils are relatively rare. Typically, when an

Figure 11.8 examples of fossils. (A) Jonathan Blair; (B) © Dr. Michael Engel, University of Kansas; (C) Martin Land/Science Source; (D) © Pixtal/SuperStock; (E) Courtesy of Stan Celestian/Glendale Community College Earth Science Image Archive; (in text) Natural History Museum, London/Science Photo Library/Science Source.

B. Extinct wasp encased in amber, which is ancient tree sap. this 9-mm-long insect lived about 20 million years ago.

A. Fossil skeleton of an ichthyosaur that lived about 200 million years ago. these marine reptiles were about the same size as modern porpoises, breathed air like them, and probably swam as fast, but the two groups are not closely related.

C. Fossilized leaf from a 260-million-year-old Glossopteris, a type of plant called a seed fern.

D. Ancient footprints of a theropod, a type of carnivorous dinosaur that arose 250 million years ago. Tyrannosaurus rex was a theropod.

e. Coprolite (fossilized feces). Fossilized food remains and parasitic worms in coprolites offer clues about the diet and health of extinct species. A foxlike animal excreted this one.

EvIDENCE oF EvolutIoN ChAPter 11 197

organism dies, its body is quickly eaten by predators, scavengers, or both. Uncon- sumed remains decompose in the presence of moisture and oxygen, so they can only endure if they dry out, freeze, or become encased in an air-excluding material such as sap, tar, or mud. Fossils that do form are often crushed or scattered by erosion and other geologic assaults. In order for us to know about an extinct species that existed long ago, we have to find a fossil of it. At least one specimen had to escape being eaten, and be preserved before it decomposed. Its burial site also had to per- sist intact, and end up in a place that we can find today.

Most ancient species had no hard parts to fossilize, so we do not find much evidence of them. For example, there are many more fossils of bony fishes and hard- shelled mollusks than fossils of soft-bodied animals (such as jellyfishes and worms) that were probably much more numerous in life. Also think about relative numbers of organisms. Fungal spores and pollen grains are typically released by the billions. By contrast, the earliest humans lived in small bands and few of their offspring survived. The odds of finding even one fossilized human bone are much smaller than the odds of finding a fossilized fungal spore. Finally, imagine two species, one that existed only briefly and the other for billions of years. Which is more likely to be represented in the fossil record?

Despite these challenges, the fossil record is substantial enough to help us reconstruct large-scale patterns in the history of life.

Radiometric Dating Atoms of a radioisotope become atoms of other ele- ments—daughter elements—as their nucleus disintegrates. This radioactive decay is not influenced by temperature, pressure, chemical bonding state, or moisture; it is influenced only by time. Thus, like the ticking of a perfect clock, each type of

Abundance of iridium in the K–Pg Boundary Layer

In the late 1970s, geologist Walter Alvarez was investigating the composition of the K–Pg boundary sequence in different parts of the world. He asked his father, Nobel Prize–winning physicist luis Alvarez, to help him analyze the elemental composition of the layer.

the Alvarezes and their colleagues tested samples of the layer taken from formations in Italy and Denmark. the researchers discovered that the K–Pg boundary sequence contains a much higher iridium content than the surround- ing rock layers. some of their results are shown in Figure 11.10.

Iridium belongs to a group of elements that are much more abundant in asteroids and other solar system materials than they are in Earth’s crust, so the Alvarez group concluded that the K–Pg boundary sequence must have originated with extraterrestrial material. they calculated that an asteroid about 14 kilometers (8.7 miles) in diameter would contain enough iridium to account for the extra iridium in the K–Pg boundary sequence.

1. What was the iridium content of the K–Pg boundary layer? 2. What was the difference in iridium content between the boundary

layer and the sample taken 0.7 meters above the layer?

Figure 11.10 Abundance of iridium in and near the K–Pg boundary sequence. left, luis and Walter Alvarez with a section of the boundary. the researchers tested the iridium content of many rock samples above, below, and at this boundary in different parts of the world. Right, some of the Alvarezes’ results from stevns Klint, Denmark. sample depths are given as meters above or below the boundary. * ppb, parts per billion.

the iridium content of an average Earth rock is 0.4 ppb. the aver- age meteorite contains about 550 ppb iridium. Lawrence Berkeley National Laboratory.

Digging Into Data

Figure 11.9 Fossil hunting. Fossil hunters found this fossilized trilobite (an ancient marine relative of centipedes) in a shale formation in yoho National Park, British Columbia. Fossils are most often found in layered sedimentary rock. this type of rock forms over hundreds of millions of years, often at the bottom of a sea. Geologic processes can tilt the rock and lift it far above sea level, where the layers become exposed by the erosive forces of water and wind. © Michael Melford/National Geographic Creative.

sample Depth

Average Abundance of Iridium (ppb)*

0.30

+ 2.7 m < 0.3

boundary layer 41.6 + 0.7 m 0.36

– 0.5 m – 5.4 m

0.25

+ 1.2 m < 0.3

198

radioisotope decays at a constant rate. The time it takes for half of the atoms in a sample of radioisotope to decay is called half-life (Figure 11.11). Half-life is a char- acteristic of each radioisotope. For example, radioactive uranium 238 decays into thorium 234, which decays into something else, and so on until it becomes lead 206. The half-life of the decay of uranium 238 to lead 206 is 4.5 billion years.

The predictability of radioactive decay can be used to find the age of a volca- nic rock (the date it solidified). Rock forms from magma, which is a hot, molten material deep under Earth’s surface. Atoms swirl and mix in this material. When magma cools, for example after reaching the surface as lava, it hardens and becomes rock. Different kinds of minerals crystallize in the rock as it hardens, each with a characteristic structure and composition. For example, the mineral called zircon consists mainly of orderly arrays of zirconium silicate molecules (ZrSiO4). Some of the molecules in a newly formed zircon crystal have uranium atoms substituted for zirconium atoms, but never lead atoms. However, uranium decays into lead at a pre- dictable rate. Thus, over time, uranium atoms disappear from a zircon crystal, and lead atoms accumulate in it. The ratio of uranium atoms to lead atoms in a zircon crystal can be measured precisely, and that ratio can be used to calculate how long ago the crystal formed (its age).

Figure 11.11 Half-life.

Figure 11.12 The oldest Earth rock. Dr. Simon Wilde holds a 4.4 billion-year-old speck of zircon embedded in protective plastic. AP Images/Andy Manis.

half-life Characteristic time it takes for half of a quantity of a radioisotope to decay.

radiometric dating Method of estimating the age of a rock or fossil by measuring the content and propor- tions of a radioisotope and its daughter elements.

Figure It Out: How much of any radioisotope remains after two half-lives have passed? Answer: 25 percent

100

newly formed rock or recent remains

after one half-life

after two half-lives

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Figure 11.13 Example of how radiometric dating can be used to find the age of a carbon- containing fossil. Carbon 14 (14C) is a radioisotope of carbon that decays into nitrogen. It forms in the atmo- sphere and combines with oxygen to become CO2, which enters food chains by way of photosynthesis. (A) © PhotoDisc/Getty Images.

A. Long ago, 14C and 12C were incorporated into the tissues of a nautilus. Both carbon isotopes were part of organic molecules in the animal’s food. 12C is stable and 14C decays, but the proportion of the two isotopes in the nautilus’s tissues remained the same. Why? The nautilus continued to gain both types of carbon atoms in the same proportions from its food.

B. The nautilus stopped eating when it died, so its body stopped gaining carbon. The 12C atoms in its tissues were stable, but the 14C atoms (represented as red dots) were decaying into nitrogen atoms. Thus, over time, the amount of 14C decreased relative to the amount of 12C. After 5,730 years, half of the 14C had decayed; after another 5,730 years, half of what was left had decayed, and so on.

C. Fossil hunters discover the fossil and measure its content of 14C and 12C . They use the ratio of these isotopes to calculate how many half-lives have passed since the organism died. For example, if its 14C to 12C ratio is one-eighth of the ratio in living organisms, then three half-lives (1/2)3 must have passed since it died. Three half-lives of 14C is 17,190 years.

EvidEncE of Evolution Chapter 11 199

Take-Home Message 11.4 What do rocks and fossils have to do with biology?

• Sedimentary rock holds evidence of the historical context of fossils embedded in it. • fossils are a stone-hard historical record of ancient life. the fossil record will never

be complete, but even so it is substantial enough to help us reconstruct patterns and trends in the history of life.

• the predictability of radioisotope decay can be used to estimate the age of rock layers and fossils in them. Radiometric dating helps evolutionary biologists retrace changes in ancient lineages.

50 cm

C. Dorudon atrox, an ancient whale that lived about 37 million years ago. its tiny, artiodactyl-like ankle bones were much too small to have supported the weight of its body on land, so this animal had to be fully aquatic.

D. Modern cetaceans such as the sperm whale have remnants of a pelvis and leg, but no ankle bones.

a. Elomeryx, a small terrestrial animal that lived about 30 million years ago. this is a member of the same artio- dactyl group (even-toed hooved mammals) that gave rise to modern representatives, including hippopotamuses. Elomeryx is thought to resemble a 60-million-year-old ancestor that it shares with whales.

Figure 11.14 Comparison of cetacean skeletons. the ancestor of whales was an artiodactyl that walked on land. over millions of years, the lineage transitioned from life on land to life in water, and as it did, bones of the hind limb (highlighted in blue) became smaller. (B left and right) © Phillip Gingerich, University of Michigan.

We have just described radiometric dating, a method that can reveal the age of a material by measuring its content of a radioisotope and daughter elements. The oldest known terrestrial rock, a tiny zircon crystal found in Australia, formed 4.4 billion years ago (Figure 11.12).

Fossils that still contain carbon can be radiometrically dated by measuring the ratio of carbon isotopes in them (Figure 11.13). Most of the 14C in a fossil will have decayed after about 60,000 years. The age of fossils older than that can be estimated by dating volcanic rock formations above and below the fossil-containing layer.

Missing Links The discovery of intermediate forms of cetaceans (an order of animals that includes whales, dolphins, and porpoises) offers an example of how fossil finds and radiometric dating can be used to reconstruct evolutionary history. For some time, evolutionary biologists had thought that the ancestors of modern cetaceans walked on land, then took up life in the water. Evidence in support of this line of thinking includes a set of distinctive features of the skull and lower jaw that cetaceans share with some kinds of ancient carnivorous land animals. DNA sequence comparisons indicate that the ancient land animals were probably artio- dactyls, hooved mammals with an even number of toes (two or four) on each foot (Figure 11.14A). Modern representatives of the artiodactyl lineage include camels, hip popotamuses, pigs, deer, sheep, and cows.

Until recently, no one had discovered fossils demonstrating gradual changes in skeletal features that would have accompanied a transition of whale lineages from terrestrial to aquatic life. These intermediate forms had to exist, because a represen- tative fossil skull of an ancient whalelike animal had been discovered, but without a complete skeleton the rest of the story remained speculative.

Then, in 2000, Philip Gingerich and his colleagues unearthed complete fossilized skeletons of two ancient whales. They found Rodhocetus kasrani (Fig- ure 11.14B) embedded in a 47-million-year-old rock formation in Pakistan, and Dorudon atrox (Figure 11.14C), in a 37-million-year-old formation in Egypt. Both fossil skeletons had whalelike skull bones, as well as intact ankle bones. The ankle bones of both fossils have distinc tive features in common with those of extinct and modern artiodactyls. Modern cetaceans do not have even a remnant of an ankle bone (Figure 11.14D).

The proportions of limbs, skull, neck, and thorax indicate Rodhocetus swam with its feet, not its tail. Like modern whales, Dorudon was clearly a fully aquatic tail-swimmer: The entire hind limb was only about 12 centimeters (5 inches) long, much too small to have supported the animal’s 5-meter (16-foot) body out of water.

B. Rodhocetus kasrani, an ancient whale that lived about 47 million years ago. its distinctive ankle bones are evidence of a close evolutionary connection to artiodactyls. Artiodactyls are defined by the unique “double-pulley” shape of the bone (right) that forms the lower part of their ankle joint.

Rodhocetus antelope

ankle bones

2 cm

2 m

50 cm

fault trench trenchridge hot spot

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11.5 Drifting Continents REMEMBER: A hypothesis is a testable explanation for a natural phenomenon (Section 1.5). The scientific community consists of critically thinking people trying to poke holes in one another’s ideas (1.6).

Wind, water, and other erosive forces continuously sculpt Earth’s surface, but they are only part of a much bigger picture of geological change. Earth itself also changes dramatically. Consider that all continents on Earth today were once part of a bigger supercontinent—Pangea—that split into fragments and drifted apart. The idea that continents move around, originally called continental drift, was proposed in the early 1900s to explain why the Atlantic coasts of South America and Africa seem to “fit” like jigsaw puzzle pieces, and why the same types of fossils occur in identi- cal rock formations on both sides of the Atlantic Ocean. It also explained why the magnetic poles of gigantic rock formations point in different directions on different continents. As magma solidifies into rock, some iron-rich minerals in it become magnetic, and their magnetic poles align with Earth’s poles when they do. If the continents never moved, then all of these ancient rocky magnets should be aligned

geologic time scale Chronology of Earth’s history.

Gondwana Supercontinent that existed before Pan- gea, more than 500 million years ago.

Pangea Supercontinent that began to form about 300 million years ago; broke up 100 million years later.

plate tectonics theory Theory that Earth’s outermost layer of rock is cracked into plates, the slow move- ment of which conveys continents to new locations over geologic time.

At oceanic ridges, magma (red) welling up from Earth’s interior drives the movement of tectonic plates. New crust spreads outward as it forms on the surface, forcing adjacent tectonic plates away from the ridge and into trenches elsewhere.

At trenches, the advancing edge of one plate plows under an adjacent plate and buckles it.

Faults are ruptures in Earth’s crust where plates meet. The diagram shows a rift fault, in which two plates move apart. The aerial photo on the right shows a strike-slip fault, in which two abutting plates slip against one another in opposite directions.

Magma ruptures a tectonic plate at what are called “hot spots.” The Hawaiian Islands have been forming from magma that continues to erupt at a hot spot under the Pacific Plate.

123 4

Figure 11.15 Plate tectonics. Huge pieces of Earth’s outer layer of rock slowly drift apart and collide. As these plates move, they convey continents around the globe. Right, © Kevin Schafer/Corbis.

The San Andreas Fault, which extends 800 miles through California, marks the boundary between two tectonic plates.

EvIDENCE oF EvolutIoN ChAPter 11 201

north-to-south, like compass needles. Indeed, the magnetic poles of rocks in each formation are aligned with one another, but the alignment is not always north-to- south. Either Earth’s magnetic poles veer dramatically from their north–south axis, or the continents wander.

Continental drift was initially greeted with intense skepticism because there was no known mechanism for continents to move. Then, in the late 1950s, deep-sea explorers found immense ridges and trenches stretching thousands of kilometers across the seafloor. The discovery led to the plate tectonics theory, which explains how continents move (Figure 11.15). By this theory, Earth’s outer layer of rock is cracked into huge plates, like a gigantic cracked eggshell. Magma welling up at an undersea ridge

or continental rift at one edge of a plate pushes old rock at the opposite edge into a trench

. The movement is like that of a colossal conveyor belt that slowly transports continents on top of it to new locations. The plates move no more than 10 centimeters (4 inches) a year—about half as fast as your toenails grow—but it is enough to carry a continent all the way around the world after 40 million years or so.

Evidence of tectonic movement is all around us, in faults 3

and other geologi- cal features of our landscapes. For example, volcanic island chains (archipelagos) form as a plate moves across an undersea hot spot. These hot spots are places where magma ruptures a tectonic plate

. The fossil record also provides evidence in support of plate tectonics. Consider

an unusual geological formation that occurs in a belt across Africa. The sequence of rock layers in this formation is so complex that it is quite unlikely to have formed more than once, but identical sequences also occur in huge belts that span India, South America, Madagascar, Australia, and Antarctica. Across all of these con- tinents, the layers are the same ages. They also hold fossils found nowhere else, including remains of the seed fern Glossopteris (pictured in Figure 11.8C), which lived 299–252 million years ago, and an early reptile called Lystrosaurus that existed 270–225 million years ago. The unusual layered rock formation that contains fossils of these organisms probably formed in one long belt on a single continent that later broke up.

We have evidence of at least five supercontinents that formed and split up again since Earth’s outer layer of rock solidified 4.55 billion years ago. One of them, a supercontinent called Gondwana, formed about 600 million years ago. Over the next 300 million years, Gondwana wandered across the South Pole, then drifted north until it merged with another supercontinent to form Pangea 300 million years ago (Figure 11.16). Most of the landmasses currently in the Southern Hemisphere as well as India and Arabia were once part of Gondwana. Some modern species, including the birds pictured in Figure 11.2, live only in these places.

Geologic changes brought on by plate tectonics would have had a profound impact on life. For example, when two continents collided into one, they brought together organisms that had been living apart on the separate landmasses, and physically separated organisms living in an ocean. When one continent broke up, organisms living on it would have been separated, and those living in different parts of the ocean would have come together. Events like these have been a major driving force of evolution, as you will see in the next chapter.

Putting Time Into Perspective Similar sequences of sedimentary rock layers occur around the world. Transitions between the layers mark boundaries between great intervals of time in the geologic time scale, which is a chronology of Earth’s history. Each layer’s composition offers clues about conditions on Earth during the

Figure 11.16 reconstructions of ancient earth. mya: million years ago. © Ron Blakey and Colorado Plateau Geosystems, Inc.

600 mya

340 mya

200 mya

150 mya

present

Gondwana

430 mya

Pangea

240 mya

65 mya

High atmospheric oxygen level fosters giant arthropods. Spore-releasing plants dominate. Age of great lycophyte trees; vast coal forests form. Ears evolve in amphibians; penises evolve in early reptiles (vaginas evolve later, in mammals only).

Radiations of marine invertebrates. First appearances of land fungi, vascular plants, bony fishes, and perhaps terrestrial animals (millipedes, spiders).

Kaibab Limestone

Toroweap Formation

Coconino Sandstone

Hermit Shale

Redwall Limestone

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Triassic

PermianPaleozoic

Carboniferous

Devonian

Silurian

Ordovician

Cambrian

3,800–2,500 mya. Origin of bacteria and archaea.

Supercontinent Pangea and world ocean form. Adaptive radiation of conifers. Cycads and ginkgos appear. Relatively dry climate leads to drought-adapted gymnosperms and insects such as beetles and flies.

Age of dinosaurs. Lush vegetation; abundant gymnosperms and ferns. Birds appear. Pangea breaks up.

Climate very warm. Dinosaurs continue to dominate. Important modern insect groups appear (bees, butterflies, termites, ants, and herbivorous insects including aphids and grasshoppers). Flowering plants originate and become dominant land plants.

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Land tetrapods appear. Explosion of plant diversity leads to tree forms, forests, and many new plant groups including lycophytes, ferns with complex leaves, seed plants.

Major period for first appearances. The first land plants, fishes, and reef-forming corals appear. Gondwana moves toward the South Pole and becomes frigid.

Earth thaws. Explosion of animal diversity. Most major groups of animals appear (in the oceans). Trilobites and shelled organisms evolve.

Oxygen accumulates in atmosphere. Origin of aerobic metabolism. Origin of eukaryotic cells, then protists, fungi, plants, animals. Evidence that Earth mostly freezes over in a series of global ice ages between 750 and 600 mya.

4,600–3,800 mya. Origin of Earth’s crust, first atmosphere, first seas. Chemical, molecular evolution leads to origin of life (from protocells to anaerobic single cells).

Tropics, subtropics extend poleward. Climate cools; dry woodlands and grasslands emerge. Adaptive radiations of mammals, insects, birds.

Modern humans evolve. Major extinction event is now under way.

Recovery from the major extinction at end of Permian. Many new groups appear, including turtles, dinosaurs, pterosaurs, and mammals.

Major extinction event Flowering plants diversify; sharks evolve. All dinosaurs and many marine organisms disappear at the end of this epoch.

Eon Era Period Epoch mya* Major Geologic and Biological Events

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202 Unit 3 EvolutIoN AND DIvERsIty

time the layer was deposited. Fossils in the layers are a record of life during that period of time (Figure 11.17).

Take-Home Message 11.5 how has earth changed over geological time?

• over geologic time, movements of Earth’s crust have caused dramatic changes in con- tinents and oceans. the changes profoundly influenced the course of life’s evolution.

Figure 11.17 the geologic time scale (above) corre- lated with sedimentary rock exposed by erosion in the Grand Canyon (opposite). Red triangles mark times of great mass extinctions. “First appearance” refers to appearance in the fossil record, not necessarily first appearance on Earth. * mya: million years ago. Dates are from the International Commission on stratigraphy, 2014. Photo, © Michael Pancier.

Figure it Out: Which formation is marked with the in the photo? Answer: tapeats sandstone