Written Assignment 2

As Mendel saw it, the world of genetics was straightforward. Each of the traits he studied was coded for by a single gene with two alleles—one completely dominant and one recessive—and with no environmental effects. We should be so lucky. In this and the following sections we build up a more complex model of how genes influence the building of bodies. We begin with the observation that the phenotype of heterozygous individuals sometimes differs from that of either of the homozygotes for the trait, and instead reflects the influence of both alleles rather than a clearly dominant allele. One situation in which complete dominance is not observed is called incomplete dominance, in which the phenotype of a heterozygote is intermediate between the phenotypes of the two homozygotes.

We can obtain true-breeding (homozygous) lines of snapdragons with red flowers and true- breeding (homozygous) lines that produce only white flowers. When plants from these two populations are crossed, we would expect—if one allele were dominant over the other—a generation with either all red or all white flowers. Instead, such crosses always produce plants with pink flowers. Then, when we cross two plants with pink flowers, we get 1/4 red-flowered plants, 1/2 pink-flowered plants, and 1/4 white-flowered plants. How can we interpret this cross? Here we use a slightly different way of denoting genotype. The plants with white flowers have the genotype CWCW and produce no pigment. At the other extreme, the plants with red flowers have the genotype CRCR and produce a great deal of pigment. The letter C indicates that the gene codes for color, and the superscript W or R refers to an allele producing no pigment (white) or red pigment. We use these designations for the genotypes because it isn’t clear that either white or red is dominant over the other, and so neither should be represented by uppercase or lowercase. The pink flowers receive one of the pigment-producing CR alleles and one of the no-pigment-producing CW alleles, and so produce an intermediate amount of pigment. Ultimately, the intensity of pigmentation just depends on the amount of pigment chemical that is made by the flower-color genes. An example of incomplete dominance in humans can be seen in the processing of cholesterol in the bloodstream. There is a membrane receptor that allows cells (chiefly those in the liver) to remove cholesterol from the bloodstream (see Section 4.11). Individuals who carry two copies of a mutant allele, called FH, for this gene produce almost no LDL receptors. Consequently, in these individuals, circulating cholesterol levels are high and cardiovascular disease develops at a very young age. Few individuals survive past 20 years of age. This is in sharp contrast to individuals carrying two copies of the allele for normal-functioning LDL receptors, who experience significantly lower levels of circulating cholesterol. Heterozygotes, carrying one copy of the mutant FH allele and one copy of the allele for normal-functioning LDL receptors, represent an intermediate situation. They produce about half as many LDL receptors as do people who are homozygous for the normal-functioning receptor, leading to higher-than-average levels of circulating cholesterol and 10 times the risk of death from cardiovascular disease.

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A second situation in which complete dominance is not observed is called codominance, in which the heterozygote displays characteristics of both homozygotes, playfully represented in Figure 9-19 (although “shirt phenotype,” of course, has no genetic basis). In codominance, neither allele masks the effect of the other. An actual example of codominance occurs with feather color in chickens. When white chickens are crossed with black chickens, all the offspring have both white and black feathers.

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Do you know your blood type? It can be O, A, B, or AB. Each of these blood types (also called blood groups) indicates something about the physical characteristics of your red blood cells and has implications for blood transfusions—both giving and receiving blood. The blood groups are interesting from a genetic perspective because they illustrate a case of multiple allelism, in which a single gene has more than two alleles. Each individual still carries only two alleles— one from the mother and one from the father. But if you surveyed all of the alleles for this gene in the population, you would find more than just two different alleles. Inheritance of the ABO blood groups provides the simplest example of multiple allelism, because there are only three alleles. We can call these alleles IA, IB, and i (using both types of allele notation introduced earlier). The IA and IB alleles are both completely dominant to i, so individuals are considered to have blood type A whether they have the genotype IAIA or Iai. Similarly, an individual with the genotype IBIB or IBi is considered to have blood type B. If you carry two copies of the i allele, you have blood type O. The IA and IB alleles are codominant with each other, so the genotype IAIB gives rise to blood type AB. Consequently, with these three alleles in the population, individuals can be one of four different blood types: A, B, AB, or O.

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These blood-type alleles direct the production of a specific set of chemicals, called antigens. Antigens are molecules (chiefly carbohydrates bound to protein) that jut from the surface of a cell and can “turn on” a body’s defenses against foreign invaders. The IA allele directs the production of A antigens that cover the surface of red blood cells. Similarly, the IB allele directs the production of B antigens on all red blood cells. Individuals with blood type AB have red blood cells with both A and B antigens. The i allele does not code for the A antigen or the B antigen. This means that individuals with blood type O have red blood cells that have neither A nor B antigens on their surface. Antigens are like signposts in the body’s disease-fighting immune system, telling the immune system whether a cell belongs in the body or not. If a red blood cell with the wrong antigens enters your bloodstream, your immune system recognizes it as a foreign invader and destroys it. Such an attack is initiated by molecules in the bloodstream called antibodies. Individuals with only A antigens on their red blood cells produce antibodies that attack B antigens. Under normal circumstances, antibodies do not encounter a red blood cell with foreign antigens. But such an event could occur if red blood cells with foreign antigens were accidentally injected into the person’s bloodstream in a transfusion. An improper transfusion can cause destruction of red blood cells, low blood pressure, and even death. Individuals with only B antigens on their red blood cells produce antibodies that attack A antigens. Individuals with blood type O, who have neither A nor B antigens on their red blood cells, produce antibodies that attack both A and B antigens. And individuals with blood type AB don’t produce either type of antibody (or else they would have antibodies that attacked their own blood cells).

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We can deduce which blood types can be used in transfusions. Individuals with blood type O are universal donors, because their red blood cells have no A or B antigens and so do not trigger a reaction from either type of antibody. And individuals with blood type AB are universal recipients, because they do not produce antibodies to either the A or B antigen. Individuals with only B antigens on their red blood cells produce antibodies that attack A antigens. Blood type O individuals, who have neither A nor B antigens on their red blood cells, produce both antibodies that attack both A and B antigens. Individuals with blood type AB don’t produce either type of antibody (or else they would have antibodies that attack their own blood cells). From this information, we can deduce which blood types can be used in transfusions.

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Another marker on the surface of red blood cells is the Rh blood group marker. (Note that the Rh blood group is not an example of multiple allelism. A single gene with just two alleles determines the presence of the Rh marker. However, like the ABO blood groups, the Rh marker restricts the type of blood a person can receive in a transfusion.) Individuals who possess red blood cells that carry the Rh cell surface marker have one or two copies of the dominant Rh marker allele and are said to be “Rh-positive.” This “positive” (“+”) is noted along with their ABO blood type, as in “O-positive.” Individuals who have two copies of the recessive allele for this gene do not have any Rh markers, and they are described as “negative,” as in “O-negative.” If, during a blood transfusion, individuals who are Rh-negative are exposed to Rh-positive blood, their immune system attacks the Rh antigens as foreign invaders—an immune response that can vary from mild, which passes unnoticed, to severe, which can lead to death. There are many, many genes with multiple alleles—a dozen or even more alleles in some cases. In fact, one gene for eye color in fruit flies has more than 1,000 different alleles!

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Old wives’ tales suggest a couple of ways that parents can predict the ultimate height of their child. If the baby is a boy, they say to add 5 inches to the mother’s height and average that with the father’s height. If it is a girl, subtract 5 inches from the father’s height and average that with the mother’s height. Alternatively, the lore says, just take the child’s height at two years of age and double it. These prediction methods can be surprisingly accurate because genes play a strong role in influencing height; offspring do resemble their parents in measurable ways. But unlike Mendel’s pea plants, in which a single gene with two alleles determines the height of the plant, for humans and most animals, adult height—a continuously varying trait—is influenced by many different genes. Such a trait is said to be polygenic. Recent research has identified at least 180 heritable loci (gene locations) that influence adult height. For each of these loci, the alleles that a person carries play a role in determining height. Individuals with “tall” variants for more of the genes tend to be taller than those with the “tall” variants for fewer of the genes. Many height genes play roles in skeletal growth and hormone pathways. For example, a gene on chromosome 15 codes for an enzyme that converts testosterone to estrogen. This enzyme influences height because estrogen helps bones fuse at their ends and thus stop growing. The term additive effects describes what happens when the effects of the alleles of multiple genes all contribute to the ultimate phenotype. The variety of heights among humans—from very short to very tall, with every height in between—reflects the fact that height is a trait influenced by contributions from multiple genes, as well as by the environment. Many other physical traits are influenced by multiple genes, including eye color in humans. Eye color was long believed to be controlled by a single gene with a dominant brown-eye allele and a recessive blue-eye allele. But it now seems that eye color is the result of interactions between at least two genes and possibly more—a situation that makes more sense, given the continuous variation in eye color among adults.

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Many behavioral traits are influenced by multiple genes. The developmental disorder known as autism, for example, seems to be the result of alterations in numerous—perhaps as many as 10 or even 20—genes. Individuals with autism have difficulty interacting with others, particularly in making emotional connections. They also tend to have narrowly focused and repetitive interests. Autism is notoriously difficult to study, because its symptoms are so Many behavioral traits are influenced by multiple genes. The developmental disorder known as autism, for example, seems to be the result of alterations in numerous—perhaps as many as 10 or even 20—genes. Individuals with autism have difficulty interacting with others, particularly in making emotional connections. They also tend to have narrowly focused and repetitive interests. Autism is notoriously difficult to study, because its symptoms are so varied, as is their intensity. These variations may result from different combinations of the many genes involved in autism. The genes responsible for autism may also influence some desirable characteristics. This idea arose when researchers documented an overrepresentation of autism among children of parents working in the fields of engineering, physics, computer science, and math. (The researchers point out, however, that children with autism are born to parents across all professions and socioeconomic backgrounds.)

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Just as multiple genes can influence one trait, some individual genes can influence multiple, unrelated traits, a phenomenon called pleiotropy. In fact, this may be true of nearly all genes. Consider sickle-cell disease (also called sickle-cell anemia), a potentially fatal condition in which individuals produce defective red blood cells that become sickle-shaped when they lose the oxygen they carry. The defective blood cells can’t effectively transport oxygen to tissues and they accumulate in blood vessels, causing extreme pain. Individuals with sickle-cell disease suffer shortness of breath and numerous other problems that lead to a significantly reduced life span. The gene responsible for sickle-cell disease codes for part of the hemoglobin molecule, the oxygen-carrying molecule in red blood cells: HbA is the allele for normal hemoglobin, and HbS

is the abnormal, “sickle-cell” allele. Sickle-cell anemia occurs in individuals homozygous for the sickle-cell allele, HbSHbS, but not in individuals carrying at least one copy of the normal allele, HbA. (Heterozygous individuals produce both normal and sickling red blood cells, but not enough sickle-shaped cells to cause sickle-cell anemia). This hemoglobin gene is pleiotropic because, although it is just one gene, it causes multiple phenotypic effects. Individuals homozygous or heterozygous for the sickle-cell allele, HbSHbS

or HbAHbS, have abnormal hemoglobin and red blood cells, and circulatory problems. Moreover, individuals with these genotypes also are resistant to the parasite that causes malaria. The malarial parasite—which lives in red blood cells—cannot survive well in cells that carry the defective version of the hemoglobin gene. Another example of pleiotropy is the gene called CFTR, which codes for a membrane protein that serves as a channel for chloride ions. Mutations that impair the functioning of these ion channels result in the disease cystic fibrosis, with its characteristic build-up of mucus in the lungs. They also give rise to diabetes resulting from reduced pancreatic functioning and, in males, cause a deterioration of the vas deferens, leading to infertility.

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The patterns of inheritance of most traits do not differ between males and females. When a gene is on an autosome (one of the non-sex chromosomes), both males and females inherit two copies of the gene, one from their mother and one from their father. The likelihood that an individual inherits one genotype rather than another does not differ between males and females. On the other hand, traits coded for by the sex chromosomes have different patterns of expression in males and females. One of the most easily observed examples of this phenomenon is red-green color-blindness. The X chromosome in humans has a gene that carries instructions for producing the light-sensitive proteins in the eye that make it possible to distinguish between the colors red and green. If an individual has at least one functioning copy of this gene, he or she produces sufficient amounts of the protein to have normal color vision. Here’s the problem: men get only one chance to inherit the normal version of the gene that codes for red-green color vision. Because the gene is on the X chromosome, men inherit this chromosome only from their mother. Women get two chances; although a woman may inherit the defective allele from one parent, she still can inherit the normal allele from the other parent (and have normal color vision). If she inherits the defective allele from both parents, she will be red-green color-blind. As we would predict, then, the frequency of red-green color-blindness is significantly greater in males than in females. Approximately 7% to 10% of men exhibit red- green color-blindness, while fewer than 1% of women are red-green color-blind. Although men exhibit sex-linked recessive traits more frequently than do women, the situation is reversed for sex-linked dominant traits. In these cases, because females have two chances to inherit the allele that causes the trait, they are more likely to have the allele and thus exhibit the trait than are males, who have only one chance to inherit the allele.

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Why do men lose their hair? Conventional wisdom has long suggested that baldness in men is a trait they inherit from their mother. This hypothesis goes back to 1916, when Dorothy Osborn published the first scientific study putting forth heredity as a cause of baldness. In her paper, she challenged a widely held hypothesis of the time: that the wearing of hats caused baldness due to pressure on blood vessels that nourish the scalp.

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It was easy for Osborn to demonstrate that, as she put it, “the hat is not to blame.” Numerous equally wrong hypotheses persist today: “The hair follicles are clogged from shampoo and too much washing.” “Not enough blood is circulating around the scalp.” “Hair gels and other products are toxic.” What Osborn found, however, was that it’s difficult to study the inheritance patterns of baldness carefully. For starters, it’s very common—about 50% of men experience some balding by the age of 50, and 70% by age 70. (Why do these observations make conventional pedigree analysis difficult?) Also, because balding increases with age, it’s hard to know whether younger, non-bald men will go bald later or never at all. And it’s unclear whether all patterns of balding have the same underlying causes. A modern approach: In 2005, researchers studied the DNA of 391 men—including 201 balding men—from 95 families in which at least two brothers exhibited early-onset male-pattern baldness. For comparison, they also examined the DNA of additional, unrelated men who were either under the age of 40 with male-pattern baldness or were over the age of 60 and unaffected by baldness.

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The researchers found that the men with male-pattern baldness were significantly more likely to share a particular stretch of DNA on their X chromosome. The unaffected men were significantly more likely to share a different sequence of DNA. (If balding men commonly share a DNA sequence on their X chromosome, what does this tell us about the inheritance of this balding-associated DNA?) The finding that the DNA region implicated in baldness is on the X chromosome confirms the longstanding observation that male-pattern baldness is a trait passed down to men from their mothers. After all, men receive their sole X chromosome from their mother. This research resolved one long-standing debate. More important, perhaps, it illuminated an avenue for research on the treatment of male-pattern baldness. The DNA sequence associated with male-pattern baldness, it turned out, is located within the region of a single gene—a gene already suspected to play a role in triggering baldness. The sequence carries the instructions to produce a higher-than-typical amount of receptors for male sex hormones, such as testosterone. This is consistent with the finding that castrated males—who produce almost no testosterone at all—don’t go bald. What strategies for treating male-pattern baldness do these observations suggest?

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PHENYLKETONURICS: CONTAINS PHENYLALANINE It’s a very serious warning, in bold, capital letters. But it’s not next to a skull and crossbones on a glass bottle in a chemistry lab. It’s on cans of diet soda (Figure 9-25). Most of us don’t notice the warning or we ignore it. The warning is for people who have a genotype that, in the presence of the amino acid phenylalanine, can be deadly. Sometimes our bodies use phenylalanine directly to build proteins, adding it to a growing amino acid chain. At other times, phenylalanine is chemically converted into another amino acid, called tyrosine. The body may then use tyrosine as it constructs proteins and in a variety of other functions. The problem is this: at birth, some people carry two copies of a mutant version of the gene that is supposed code for the enzyme that converts phenylalanine into tyrosine. The mutant gene produces a malfunctioning enzyme, and none of the body’s phenylalanine is converted into tyrosine. Little by little, as these individuals consume phenylalanine, it builds up in their bodies. Babies born with the two mutant alleles usually begin to show symptoms within 3–6 months. Within a few years, so much accumulates that it reaches toxic levels and poisons the brain, leading to mental retardation and other serious health problems. The disease is called phenylketonuria, or PKU. Here’s where the warning label comes in. By limiting the amount of phenylalanine consumed, individuals with the two mutant alleles for processing phenylalanine can avoid the toxic buildup of the amino acid in their brain. This example highlights the fact that genes interact with the environment to produce physical characteristics. Unless you have information about both the genes and the environment, it is not usually possible to know what the phenotype will be.

Siamese cats (as well as the Himalayan rabbit) carry genes that produce dark pigmentation. These genes interact strongly with the environment and are heat-sensitive. Dark pigment is produced only in relatively cold areas of the animal’s body, while warm areas remain very light. This is why the fur on the coldest parts of the body—the ears, paws, tail, and tip of the face— becomes the darkest, while the fur on the rest of the body remains cream-colored or white. For Siamese cats living in cold climates and spending a lot of time outside, it’s interesting to notice that they become significantly darker in color during the winter months. Those that lounge indoors all winter remain lighter in color. There are thousands of other cases in which genes’ interactions with the environment influence their effects in the body. The scope of environmental influences ranges from traits with obvious environmental effects, such as body weight and its relationship with caloric intake; to those with slight environmental effects, such as fur color; and those with complex and subtle interactions with the environment, such as intelligence and personality. Given the role of environmental factors in influencing phenotypes, DNA is not like a blueprint for a house. There is nearly always significant interaction between the genotype and the environment that influences the exact phenotype produced. If this were not true, there would be no reason to invest in better schools, physical fitness regimens, nutritional monitoring, self- help efforts, or any other process by which individuals or societies try to improve people’s lives (i.e., alter phenotypes) by enriching their environment.

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