Order 1218450: A & P Chap 1-4

1

04 Genetics and cellular function

Learning Objectives • With respect to nucleic acids:

• Identify the monomers and polymers. • Compare and contrast general molecular structure.

• Define the terms genetic code, transcription and translation.

• Explain how and why RNA is synthesized.

• Explain the roles of tRNA, mRNA, and rRNA in protein synthesis.

• Define the term cellular respiration.

• With respect to glycolysis, the Krebs (citric acid or TCA) cycle, and the electron transport chain: compare and contrast energy input, efficiency of energy production, oxygen use, by-products and cellular location.

• Referring to a generalized cell cycle, including interphase and the stages of mitosis: • Describe the events that take place in each stage. • Identify cells that are in each stage. • Analyze the functional significance of each stage.

• Distinguish between mitosis and cytokinesis.

• Describe DNA replication.

• Analyze the interrelationships among chromatin, chromosomes and chromatids.

• Give examples of cell types in the body that divide by mitosis and examples of circumstances in the body that require mitotic cell division.

• Compare and contrast the processes of mitosis and meiosis.

• Provide specific examples to demonstrate how individual cells respond to their environment (e.g., in terms of organelle function, transport processes, protein synthesis, or regulation of cell cycle) in order to maintain homeostasis in the body.

• Predict factors or situations that could disrupt organelle function, transport processes, protein synthesis, or the cell cycle.

• Predict the types of problems that would occur if the cells could not maintain homeostasis due to abnormalities in organelle function, transport processes, protein synthesis, or the cell cycle.

2

DNA and RNA—The Nucleic Acids

DNA Structure

• Deoxyribonucleic acid (DNA)— long, thread-like molecule with 2 nm diameter, but varied length • 46 DNA molecules in nucleus of

most human cells • Average length about 43,000 μm

each

• DNA (and other nucleic acids) are polymers of nucleotides • Nucleotide consists of a sugar,

phosphate group, and nitrogenous base

• A single DNA nucleotide • One deoxyribose sugar • One phosphate group • One nitrogenous base

3

Nitrogenous Bases

• Purines—double ring • Adenine (A)

• Guanine (G)

• Pyrimidines—single ring • Cytosine (C)

• Thymine (T)

• Uracil (U) (not found in DNA, only found in RNA)

DNA Structure

• Phosphate and Sugar unite by covalent bonds to form “backbone”

• Nitrogenous bases of two backbones united by hydrogen bonds • A purine on one strand always bound to a pyrimidine

on the other

• A–T two hydrogen bonds

• C–G three hydrogen bonds

• Double helix shape of DNA (resembles spiral staircase)

• Law of complementary base pairing • One strand determines base sequence of other

4

Chromatin and Chromosomes

• Most human cells have 2 million μm (2m) of DNA

• Nucleosome - DNA winds around eight histone proteins (like thread around spool)

• Chromatin consists - thousands of repeating nucleosomes • Occurs as 46 chromosomes in most cells

• In nondividing cells, chromatin is so slender it cannot be seen with light microscope

• Granular appearance under electron microscope

• Chromatin thrown into complex, irregular loops and coils • 1,000 times shorter than original molecule

Chromosomes

• When preparing to divide, cell makes copy of all nuclear DNA

• Each chromosome then consists of two parallel filaments of identical DNA - sister chromatids

• Becomes visible with light microscope

• Chromatids are joined at constricted centromere • Kinetochores—proteins on each side of

centromere

5

RNA Structure and Function

• Ribonucleic acids (RNAs) – a polymer of nucleotides that resemble DNA but • Ribose sugar instead of deoxyribose • Uracil instead of Thymine

• RNA is usally single stranded and much shorter in length than DNA

• Three important RNAs for protein synthesis • Messenger RNA (mRNA) • Ribosomal RNA (rRNA) • Transfer RNA (tRNA)

Genes and Their Action

6

What Is a Gene?

• 46 human chromosomes come in two sets of 23 chromosomes (one from each parent)

• Genome—all the DNA in one 23-chromosome set • Genomics—study of the whole genome and how it affects structure and

function of the whole organism

• Genome is 3.1 billion nucleotides

• Humans have about 20,000 genes • Only about 2% of total DNA is genes • Other 98% is noncoding DNA that plays role in chromosome structure and

gene regulation

• Gene—an information-containing segment of DNA that codes for the production of a molecule of RNA that plays a role in synthesizing one or more proteins

• Amino acid sequence of a protein is determined by the nucleotide sequence in the DNA

The Genetic Code

• Body can make millions of different proteins (the proteome), from just 20 amino acids, and encoded by genes made of just four nucleotides (A, T, C, G)

• Genetic code—a system that enables these four nucleotides to code for amino acid sequences of all proteins

• Minimum code to symbolize 20 amino acids is three nucleotides per amino acid

• Base triplet - a sequence of three DNA nucleotides that stands for one amino acid

• Codon - the 3-base sequence in mRNA

• 64 possible codons available to represent the 20 amino acids • 61 code for amino acids; 3 are stop codons • Stop codons—UAG, UGA, and UAA: signal “end of

message,” like a period at the end of a sentence • Start codon—AUG codes for methionine, and begins

the amino acid sequence of the protein

7

Protein Synthesis

• All body cells, except sex cells and some immune cells, contain identical genes

• But different genes are activated in different cells

• Any given cell uses one-third to two-thirds of its genes while the rest are “dormant”

• When a gene is activated, mRNA complementary to the genes is synthesized in the nucleus • Transcription

• mRNA Migrates from the nucleus to cytoplasm where it codes for amino acids used to make protein • Translation

Transcription

• Transcription - copying genetic instructions from DNA to mRNA • RNA polymerase - binds to certain DNA sequences that

signal start (e.g., TATATA) and synthesize mRNA copy • RNA polymerase opens up the DNA helix and reads bases from

one strand of DNA • RNA polymerase rewinds the DNA helix behind it so it can be

transcribed again • Transcription stops to certain DNA sequences called the

Terminator

8

Alternative Splicing • Transcription actually makes Pre-mRNA

• Pre-mRNA has: • Intervening introns that are removed by nuclear enzymes • Exons that will form “mature” mRNA that is exported from nucleus

• Alternative splicing - variations in the way exons are spliced allow for a variety of proteins to be produced from one gene

• Finally cap (for ribosome binding) has to be added

Translation

• Translation - process that converts the language of nucleotides into the language of amino acids

• Three main participants in translation • mRNA carries code from nucleus to cytoplasm

• Transfer RNA (tRNA) delivers a single amino acid to the ribosome for it to be added to growing protein chain • Contains an anticodon - series of 3 nucleotides that

are complementary to codon of mRNA

• Attached to the correct amino acid

• Ribosomes - organelles that read the message • Found free in cytosol, on rough ER, and on nuclear

envelope

• Consist of large and small subunits, where each subunit is made of several enzymes and ribosomal RNA (rRNA) molecules

9

Translation - Initiation

• Three steps to translation: Initiation, Elongation, Termination

1. Initiation • Small ribosomal subunit binds to mRNA near cap and slide along until • Initiator tRNA (bearing methionine) pairs with start codon • Large ribosomal subunit joins the complex and the now fully formed ribosome

begins reading bases

Translation – Elongation 2. Elongation

• Next tRNA (with its amino acid) binds to ribosome while its anticodon pairs with next codon of mRNA

• Peptide bond forms between methionine and second amino acid • Ribosome slides to read next codon and releases initiator tRNA (empty) • Next tRNA with appropriate anticodon brings its amino acid to ribosome • Another peptide bond forms (between 2nd and 3rd amino acids) • Process continually repeats, extending peptide to a protein

10

Translation - Termination

• Three steps to translation: Initiation, Elongation, Termination

3. Termination • When ribosome reaches stop codon a release factor binds to it

• Finished protein breaks away from ribosome

• Ribosome dissociates into two subunits

Review of Transcription and Translation

11

Protein Processing and Secretion 1

• Protein synthesis is not finished when the amino acid sequence (primary structure) has been assembled

• Chaperone proteins help fold protein into precise secondary and tertiary structures for proper function

• Proteins to be used in the cytosol are made on free ribosomes in the cytosol

• Proteins headed for lysosomes, secretion, or integral membrane proteins are made on ribosomes on the rough ER • mRNA/ribosome migrates docks on surface of ER and

feeds polypeptide to interior

• Some post-translational modification (e.g. disulfide bridges, glycosylation) occurs in ER lumen

• When rough ER is finished with protein • Pinches off transport vesicle coated with clathrin

• Vesicles detach from ER and carry protein to the nearest cisterna of Golgi complex

Protein Processing and Secretion 2

• ER derived vesicles fuse with Golgi cisterna

• Golgi complex further modifies the protein • Often adds carbohydrate chains and

assembles glycoproteins • Golgi cisterna farthest from ER buds off

new coated Golgi vesicles containing finished protein

• Some Golgi vesicles become lysosomes

• Other Golgi vesicles become secretory vesicles and migrate to plasma membrane, fuse to it, and release their cell product by exocytosis

• Other Golgi vesicles migrate to plasma membrane, fuse to it, and deliver integral transmembrane proteins

12

Synthesizing Compounds Other Than Proteins

• Cells synthesize glycogen, fat, steroids, phospholipids, pigments, and other compounds • No genes for these products, but their synthesis is under indirect genetic

control

• They are produced by enzymatic reactions, and enzymes are proteins encoded by genes

• Example: production of testosterone (a steroid) • A cell of the testes takes in cholesterol

• Enzymatically converts it to testosterone

• Only occurs when genes for enzyme are active

DNA Replication and the Cell Cycle

13

DNA Replication • Before a cell divides, it must duplicate its DNA so it can give a complete copy of all

its genes to each daughter cell

• Since DNA controls all cellular function, this replication process must be very exact

• Law of complementary base pairing - we can predict the base sequence of one DNA strand if we know the sequence of the other

• Four steps of DNA replication: unwinding, unzipping, building new DNA strands, repackaging

1. DNA unwinds from histones

2. DNA helicase unzips segment of double helix exposing bases • Replication fork - the point of DNA opening

DNA Replication 2 • Four steps of DNA replication: unwinding, unzipping, building new DNA strands, repackaging

1. DNA polymerase builds new DNA strands • Polymerase reads exposed bases and matches complementary free nucleotides • Separate polymerase molecules work on each strand proceeding in opposite directions • DNA polymerase does make mistakes, but

• Double checks the new base pair and tends to replace incorrect, biochemically unstable pairs with more stable, correct pairs

• Result is only one error per 1 billion bases replicated - Mutation

• Some mutations cause no ill effects, others kill the cell, turn it cancerous, or cause genetic defects in future generations

2. Newly made DNA is repackaged • With thousands of polymerase molecules working simultaneously on the DNA, all 46 chromosomes are replicated in 6 to 8

hours • Millions of histones are made in the cytoplasm while DNA is replicated and they are transported into the nucleus soon after

DNA replication ends • Each new DNA helix wraps around the histones to make new nucleosomes

14

The Cell Cycle

• Cell cycle—cell’s life from one division to the next

• Includes interphase and mitotic phase

• Interphase includes three subphases • G1, S, G2

• Mitotic phase includes multiple subphases • Prophase, Metaphase, Anaphase,

Telophase

Mitosis 1

• Meiosis is cell division resulting in two daughter cells (gametes) with half the genetic information

• Mitosis is cell division resulting in two genetically identical daughter cells

• Functions of mitosis • Development of the individual from one fertilized egg to roughly 50 trillion

cells

• Growth of all tissues and organs after birth

• Replacement of cells that die

• Repair of damaged tissues

• Four phases of mitosis • Prophase, metaphase, anaphase, telophase

15

Mitosis 2 • Prophase

• Genetic material condenses into 46 compact chromosomes • Two chromatids per

chromosome

• Nuclear envelope disintegrates

• Centrioles sprout spindle fibers (long microtubules) • Spindle fibers push centriole

pairs apart

• Some spindle fibers attach to kinetochores of centromeres of chromosomes

• Metaphase • Chromosomes are aligned on

metaphase plate

• Spindle fibers complete mitotic spindle

• Shorter microtubules from centrioles complete an aster which anchors itself to inside of cell membrane

Mitosis 3

• Anaphase • Enzyme cleaves two sister

chromatids apart at centromere

• Single-stranded daughter chromosomes migrate to each pole of the cell as motor proteins in kinetochores crawl along spindle fibers

• Telophase • Chromosomes cluster on each

side of the cell

• Rough ER makes new nuclear envelope around each cluster

• Chromosomes uncoil to chromatin

• Mitotic spindle disintegrates

• Each nucleus forms nucleoli

16

Mitosis 4

• Cytokinesis—division of cytoplasm into two cells • Telophase is the end of nuclear division but

overlaps cytokinesis

• Achieved by myosin protein pulling on actin in the terminal web of cytoskeleton

• Creates cleavage furrow around the equator of cell

• Cell eventually pinches in two

Chromosomes and Heredity

17

Chromosomes and Heredity • Heredity—transmission of genetic

characteristics from parent to offspring

• Karyotype—chart of 46 chromosomes laid out in order by size

• 23 pairs—the two members of each pair are called homologous chromosomes

• 1 chromosome from each pair inherited from each parent • 22 pairs called autosomes

• Look alike and carry the same genes

• 1 pair of sex chromosomes (X and Y) • Female has homologous pair of X chromosomes • Male has one X and one much smaller Y

chromosome

• Diploid (2n) —describes any cell with 23 pairs of chromosomes (somatic cells)

• Haploid (n) —describes cells containing half as many chromosomes (23 unpaired) as somatic cells; that is, sperm and egg cells

• Fertilization restores diploid (2n) number to the fertilized egg and the somatic cells arise from it

Genes and Alleles

• Location of a particular gene on a chromosome called locus

• Different forms of gene at same locus on two homologous chromosomes called alleles

• Genotype - alleles an individual possesses for a particular trait • Homozygous individuals—two identical alleles for the trait • Heterozygous individuals—different alleles for that gene

• Phenotype - an observable trait • An allele is expressed if it shows in the phenotype of an individual

• Dominant allele (represented by capital letter) • If present, corresponding trait is usually seen in the individual • Masks effect of recessive allele • Often produces protein responsible for visible trait

• Recessive allele (represented by lowercase letter) • Corresponding trait only seen when recessive allele present on

both homologous chromosomes • Often codes for a nonfunctional variant of the protein

• Punnett square - diagram showing possible genotype and phenotype outcomes from parents of known genotype

18

Punnett Square

• Cleft (C) is dominant to uncleft chin (c)

• CC, Cc = cleft chin

• cc = uncleft chin

• Can two parents with cleft chin produce child with uncleft chin?

Sex Linkage • Sex-linked traits—carried on X or Y chromosome, and therefore tend to be

inherited by one sex more than the other • Much more common for trait to be on X, as Y as very few genes

• Recessive color blindness allele on X, no gene locus for trait on Y, so color blindness more common in men (mother is carrier in illustrated example)

19

Multiple Alleles, Codominance, and Incomplete Dominance

• Gene pool - genetic makeup of whole population (an individual can only have two alleles, but population can have many)

• Multiple alleles—more than two allelic forms of gene • Example: three alleles for ABO blood types

• IA, IB, i alleles for ABO blood types

• Codominance—both alleles equally dominant • Both are phenotypically expressed • Example: IAIB = type AB blood

• Incomplete dominance • Heterozygous individual shows phenotype intermediate

between traits each allele would have produced alone • Example: familial hypercholesterolemia