1 / 97

Chapter22 Population Genetics

Chapter22 Population Genetics.

arawn
Download Presentation

Chapter22 Population Genetics

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Chapter22Population Genetics • Individuals can carry only two different alleles of a given gene. A group of individuals can carry a large number of different alleles, give rise to a reservoir of genetic diversity. Diversity contained in the population can be measured by the Hardy-Weinberg law. Mutation is the ultimate source of genetic variation and other factors such as drift, migration, and selection can alter the amount of genetic variation in population

  2. 22.1 Population and gene pool 22.2 Calculating allele frequency 22.3 The Hardy-Weinberg law 22.4 Extension of the Hardy-Weinberg law 22.5 Using the Hardy-Weinberg law, calculating heterozygote frequency 22.6 Factors that later allele frequency in population 22.7 Natural selection 22.8 Mutation 22.9 Migration 22.10 Genetic drift 22.11 Nonrandom mating

  3. Alfred Russell Wallace and Charles Darwin first identified natural selection as the mechanism of adaptive evolution in the mid-nineteenth century, based on a series of observations of populations of organisms: • (1) Phenotypic variations exist among individuals within populations; • (2) these differences are passed from parents to offspring; • (3) more offspring are born than will survive and reproduce; and • (4) some variants are more successful at surviving and/or reproducing than others. In populations where all four factors operate, the relative abundance of the population's different phenotypes changes across generations. In other words, the population evolves.

  4. Although Wallace and Darwin described how organisms evolve by natural selection, there was no accurate model of the mechanisms responsible for variation and inheritance. Gregor Mendel published his work on the inheritance of traits in 1865, • For many years, theorists focused on developing mathematical models that would describe the genetic structure of populations. Prominent among the theoreticians who developed these models were Sewall Wright, Ronald Fisher, and J. B. S. Haldane. • Following their work, experimentalists and field workers tested the models using biochemical and molecular techniques that measure variation directly at the protein and DNA levels. These experiments examined allele frequencies and the forces that alter the frequencies, such as selection, mutation, migration, and random genetic drift. In this chapter we consider some general aspects of population genetics and also discuss other areas of genetics that relate to evolution.

  5. 22.1 Populations and Gene Pools • Members of a species often range over a wide geographic area. • A population is a group of individuals from the same species that lives in the same geographic area(孟德尔群体), and that actually or potentially interbreeds. • If we consider a single genetic locus in this population, we may find that individuals within the population have different genotypes. To study population genetics, we compute frequencies at which various alleles and genotypes occur, and how these frequencies change from one generation to the next.

  6. When we consider generational changes in alleles and genotypes, we look at gene pools. • A gene pool consists of all gametes made by all the breeding members of a populationin a single generation • Gene pool基因库    将群体中所有个体共有的全部基因定义称为一个基因库（gene pool）。 • : gametes to zygotes - next generation. alleles proportion of gametes in a gene pool

  7. 22.2 Calculating Allele Frequencies • Most genetic population researchers first measure the frequencies at which alleles occur at a particular locus. To do this, the genotypes of a large number of individuals in the population must be determined. • In some cases, researchers can infer genotypes directly from phenotypes. • In other cases, proteins or DNA sequences are analyzed to determine genotypes. • To understand how allele frequencies are calculated, we consider an example that involves HIV infection rates.

  8. In 1996, Rong Liu and colleagues discovered that two exposed-but-uninfected individuals were homozygous for a mutant allele of a gene called CC-CKR-5. • The CC-CKR-5 gene, chromosome 3, a protein called the C-C chemokine（趋化因子）receptor-5(CCR5). Chemokines are cell-surface signaling molecules found on cells in the immune system. When cells with CCR5 receptor proteins bind to chemokine signals, the cells move into inflamed tissues to fight infection. • The CCR5 protein is a co-receptor for strains of HIV-1. To gain entry into cells, a protein called Env (short for envelope protein) on the surface of HIV-1 binds to the CD4 protein on the surface of the host cell. Binding to CD4 causes Env to change shape and form a second binding site. This second site binds to CCR5, which in turn initiates the fusion of the viral protein coat with the host cell membrane. The merging of viral envelope with cell membrane transports the HIV viral core into the host cell's cytoplasm.

  9. The mutant allele of the CCR5 gene contains a 32-bp deletion in one of its coding regions. As a result, the protein encoded by the mutant allele is shortened and made nonfunctional. The protein never makes it to the cell membrane, so HIV-1 cannot enter these cells. The gene's normal allele is called CCR51 (or 1) and its allele with the 32-bp deletion is called CCK5- 32 (or 32), The two uninfected individuals described by Liu both had the genotype 32/ 32. • As a result, they had no CCR5 on the surface of their cells, and were resistant to infection by strains of HIV-1 that require CCR5 as a co-receptor.

  10. At least three 32/32individuals who are infected with HIV-1 have been found. Curiously, researchers have not discovered any adverse effects associated with this genotype. Heterozygotes with genotype 1/32 are susceptible to HIV-1 infection, but evidence suggests that they progress more slowly to AIDS. Table 22.1 summarizes the genotypes possible at the CCRS locus, and the phenotypes associated with each. Table 22.1 CCRS genotype and phenotype 1/ 1 susceptible to sexually transmitted HIV-1 strain 1/ 32susceptible, but may progress to AIDS slowly 32/ 32 resistant to most sexually transmitted HIV-1s

  11. The discovery of the CCR5-  32allele, and the fact that it provides some protection against AIDS, generates two important questions: Which human populations harbor the 32allele, and how common is it? To address these questions, several teams of researchers surveyed a large number of people from a variety of populations. Genotypes were determined by direct analysis of DNA (Figure 22-1).

  12. Figure 22-2 shows the frequency of the CCR5-A32 allele in the 18 European populations surveyed. The studies show that populations in Northern Europe have the highest frequencies of the A32 allele. The frequency of the allele declines to the south and to the west. In populations without European ancestry the A32 allele is essentially absent. The highly patterned global distribution of the A32 allele presents an evolutionary puzzle that we'll return to later in the chapter

  13. 22.3 The Hardy-Weinberg Law • The large variation in the frequency of the CCR5-A32allele among populations raises a number of questions. For example, can we expect the allele to increase in populations in which it is currently rare? Population genetics explores such questions using a mathematical model developed independently by the British mathematician Godfrey H. Hardy and the German physician Wilhelm Weinberg. • This model, called the Hardy-Weinberg law, shows what happens to allele and genotype in an "ideal" population (free of many of the complications that affect real populations) using a set of simple assumptions.

  14. 1.Individuals of all genotypes have equal rates of survival and equal reproductive success; that is, there is no selection. • 2.No new alleles are created or converted from one allele into another by mutation. • 3.Individuals do not migrate into or out of the population. • 4.The population is infinitely large, which in practicalterms means that the population is large enough thatmate randomly sampling errors and other random effects are negligible. • 5.Individuals in the population mate randomly

  15. The Hardy-Weinberg law demonstrates that an "ideal" population has these properties: • 1.The frequency of alleles does not change from generation to generation; in other words, the population does not evolve. • 2.After one generation of random mating, offspring genotype frequencies can be predicted from the parent allele frequencies. • What makes the Hardy-Weinberg law useful, however, is its assumptions. By specifying the assumptions under which the population cannot evolve, the Hardy-Weinberg law identifies the real-world forces that cause allele frequencies to change. In other words, by holding certain conditions constant, the Hardy-Weinberg law isolates the forces of evolution.

  16. A Demonstration of the Law • To demonstrate how the Hardy-Weinberg law works, we begin with a specific case, and then consider the general case. In both examples, we focus on a single locus with two alleles, A and a. • Imagine a population in which the frequency of allele A, in both eggs and sperm, is 0.7, ais 0.3, Note that 0.7 + 0.3 = 1, indicating that all the alleles for gene A present in the gene pool are accounted for. We assume, per Hardy-Weinberg requirements, that individuals mate randomly, which we visualize as follows. We place all the gametes in the gene pool, in a barrel and stir. We then randomly draw eggs and sperm from the barrel and pair them to make zygotes. What genotype frequencies does this give us?

  17. The probability of genotype AAwill occur 49% Aais 0.21 + 0.21 = 0.42 = 42 % aa is 9 %

  18. We started with the frequency of a particular allele in a specific gene pool and calculated the probability that certain genotypes would be produced from this pool. When the zygotes develop into adults and reproduce, what will be the frequency of distribution of alleles in the new gene pool? • Recall that under the Hardy-Weinberg law, we assume that all genotypes have equal rates of survival and reproduction. This means that in the next generation, all genotypes contribute equally to the new gene pool.

  19. The AA individuals 49% carry allele A, • Likewise, Aa individuals 42% Half (0.5) of these gametes carry allele A. • Frequency of allele A in the gene pool is 0.49 + (0.5) 0.42 = 0.7. • The other half carry allele a. • The aa individuals 9 % (0.5) 0.42 + 0.09 = 0.3. As a check on our calculation, note that 0.7 + 0.3 = 1.0, accounting for all of the gametes in the gene pool of the new generation.

  20. We have arrived back where we began, with a gene pool in which the frequency of allele A is 0.7 and the frequency of allele a is 0.3. • These calculations demonstrate the Hardy-Weinberg law: Allele frequencies in our population do not change from one generation to the next, and after just one generation of random mating the genotype frequencies can be predicted from the allele frequencies. In other words, this population does not evolve. • use variables instead of, numerical values for the allele frequencies. • A -p a -q, p + q = 1. • Zygote that carry allele A is p X p. AA =p2. Aa=2pq. aa=q2

  21. Figure 22-4 shows these calculations • p2 + 2pq + q2 = 1

  22. For our general case we ask what the allele frequencies in the new gene pool will be when these zygotes develop into adults and reproduce. All gametes from AA individuals carry allele A, as do half of the gametes from Aa individuals. Thus we predict that the frequency of allele A in the new gene pool will be • p2 + (1/2) 2pq = p2 + pq Or P2 + p(l ~ p) = p2 + P - P2 = P • Likewise, the frequency of allele a in the new gene pool will be • (1/2)2pq + q2 = pq + q2 Or (1 - q)q + q2 = q - q2 + q2 = q

  23. Consequences of the Law • The Hardy-Weinberg law has several important consequences. • First, it shows that dominant traits do not necessarily increase from one generation to the next. • Second, it demonstrates that genetic variability can be maintained in a population since, once established in an ideal population, allele frequencies remain unchanged. • Third, if we invoke Hardy-Weinberg assumptions, then knowing the frequency of just one genotype enables us to calculate the frequencies of all other genotypes. This relationship is particularly useful in human genetics because we can now calculate the frequency of heterozygous carriers for recessive genetic disorders even when all we know is the frequency of affect­ed individuals

  24. We began this discussion by asking whether we can expect the CCR5-32 allele to increase in populations in which it is currently rare. • From what we now know about the Hardy-Weinberg law, we can say for the general case that if (l) individuals of all genotypes have equal rates of survival and reproduction, (2) there is no mutation, (3) no one migrates into or out of the population, (4) the population is extremely large, (5) individuals in the population choose their mates randomly, then the frequency of the 32 allele will not change. • Of course, for real populations, few if any of these assumptions are likely to hold.

  25. The general case demonstrates the most important role of the Hardy-Weinberg law: It is the foundation upon which population genetics is built. By showing that "ideal" populations do not evolve, we can use the Hardy-Weinberg law to identify forces that do cause populations to evolve.

  26. when the assumptions of the Hardy-Weinberg law are broken—- • because of natural selection, • mutation, migration, and • random sampling errors (also known as genetic drift)—the allele frequencies in a population may change from one generation to the next. Nonrandom mating does not, by itself, alter allele frequencies, but by altering genotype frequencies it indirectly affects the course of evolution. The Hardy-Weinberg law tells geneticists where to look to find the causes of evolution in real populations. • We return to the CCR5-A32 allele later in the chapter to see how a population genetics perspective has generated fruitful hypotheses for further research.

  27. Testing for Equilibrium • One way we establish whether one or more of the Hardy-Weinberg assumptions do not hold in a given population is by determining whether the population's genotypes are in equilibrium. To do this, we first determine the frequencies of the genotypes, either directly from the phenotypes (if heterozygotes are recognizable) or by analyzing proteins or DNA sequences. We then calculate the allele frequencies from the genotype frequencies, as demonstrated earlier. Finally, we use the parents' allele frequencies to predict the offspring's genotype frequencies. According to the Hardy-Weinberg law, the genotype frequencies are predicted to fit the p2 + 2pq + q2= 1 relationship. If they do not, then one or more of the assumptions are invalid for the population in question.

  28. We will use the CCR5 genotypes of a population in Britain to demonstrate the Hardy-Weinberg law. The population includes 283 individuals, of which 223 have genotype 1/1, 57 have genotype 1/A32, and 3 have genotype A32/A32. These numbers represent genotype frequencies of 223/283 = 0.788, 57/283 = 0.201, and 3/283 = 0.011, respectively. From the genotype frequencies we compute the CCR5I allele frequency as 0.89 and the frequency of the CCR5-A32 allele as 0.11. From these allele frequencies, we can use the Hardy-Weinberg law to determine whether this population is in equilibrium. The allele frequencies predict the genotype frequencies as follows: • Expected frequency of genotype 1/1 = p2 = (0.89)2 - 0.792 • Exp genotype 1/A32 - 2pq = 2(0.89)(0.11) = 0.196 • Expected genotype A32IA32 = q2 = (0.11 )2 = 0.012

  29. These expected frequencies are nearly identical to the observed frequencies. Our test of this population has failed to provide evidence that Hardy-Weinberg assumptions are being violated. This conclusion is confirmed by a X2 analysis (see Chapter 3). • The X2value in this case is tiny: 0.00023. To be statistically significant at even the most generous, accepted level, p = 0.05, the X2 value would have to be 3.84. (In a test for Hardy-Weinberg equilibrium, the degrees of freedom are given by k - 1 - m, where k is the number of genotypes and m is the number of independent allele frequencies estimated from the data.

  30. On the other hand, if the Hardy-Weinberg test had demonstrated that the population is not in equilibrium, it would indicate that one or more assumptions are not being met. To illustrate this, imagine two hypothetical populations, one living on East Island,all 1/1, 100 % other living on West Island, A32/A32, 100 % • Now imagine that 500 people from each island move to the previously uninhabited Central Island.

  31. However, it would take only one generation of random mating on Central Island to bring the offspring to the expected allele frequencies, as shown in Figure 22-5. Therese Markow and colleagues documented a real human population that is not in Hardy-Weinberg equilibrium. These researchers studied 122 Havasupai, a population of Native Americans in Arizona. They determined the genotype of each Havasupai individual at two loci in the major histocompatibility complex (MHC). These genes, HLA-A and HLA-8, encode proteins that are involved in the immune system's discrimination between self and nonself. The immune systems of individuals heterozygous at MHC loci appear to recognize a greater diversity of foreign invaders and thus may be better able to fight disease.

  32. Markow and colleagues observed significantly more individuals who are heterozygous at both loci, and significantly fewer homozygous individuals than would be expect­ed under the Hardy-Weinberg law. Violation of either or both of two Hardy-Weinberg assumptions could explain the excess of heterozygotes among the Havasupai. • First, Havasupai fetuses, children, and adults who are heterozygous for HLA-A and HLA-B may have higher rates of survival than individuals who are homozygous. • Second, rather than choosing their males randomly, Havasupai people may somehow prefer mates whose MHC genotypes differ from their own.

  33. 22.4 Extensions of theHardy-Weinberg Law • We commonly find several alleles of a single locus in a population. The ABO blood group in humans (discussed in Chapter 4) is such an example. The locus I (isoagglutinin) has three alleles (IA, IB, and IO), 6 genotypic • A and B codominant, both dominant to O. • AA , AO phenotypic identical, • BB and BO ” only 4 distinguished • Let p, q, and r represent A, B, and 0, respectively. • p + q + r = 1

  34. Under Hardy-Weinberg assumptions, the frequencies of the genotypes are given by • (P + q + r)2 =p2 + q2+r2 + 2pq + 2r + 2qr = 1 • If we know the frequencies of blood types for a population, we can then estimate the frequencies for the three alleles of the ABO system. • E.g., in one population sampled, • A = 0.53, B = 0.13,AB - 0.08, and O = 0.26. Because the O allele is recessive, the population's frequency of type O blood equals the proportion of the recessive genotype r2. Thus, • r2 = 0.26 ,r = √.26 =.51

  35. Using r, we can estimate the allele frequencies for the A and B alleles. The A allele is present in two genotypes, AA and AO. The frequency of the AA genotype is represented by p2, and the AO genotype by Ipr, Therefore, the combined fre­quency of type A blood and type O blood is given by • p2+ 2pr + r2= 0.53 + 0.26 • If we factor the left side of the equation and take the sum of the terms on the right, we get • (p + r)2 = 0.79 • p + r = √0./79, p = 0.89 - r ,p = 0.89 - 0.51 = 0.38 • Having estimated p and r, the frequencies of allele A and allele 0, we can now estimate the frequency for the B allele: • p + q + r = 1 q = 1 - p - r • = 1 - 0.38 - 0.51= 0.11

  36. 22.5 Using the Hardy-Weinberg law: Calculating Heterozygote Frequency • In one application, the Hardy-Weinberg law allows us to estimate the frequency of heterozygotes in a population. The frequency of a recessive trait can usually be determined by counting such individuals in a sample of the population. With this information and the Hardy-Weinberg law, we can then calculate the allele and genotype frequencies. Cystic fibrosis, an autosomal recessive trait, has an incidence of about 1/2500 = 0.0004 in people of northern European ancestry. Individuals with cystic fibrosis are easily distinguished from the population at large by such symptoms as salty sweat,excess amounts of thick mucus in the lungs, and susceptibility to bacterial infections. Because this is a recessive trait, individuals with cystic fibrosis must be homozygous.

  37. Their frequency in a population is represented by q2, provided that mating has been random in the previous generation. The frequency of the recessive allele therefore is • q = √q2 = √ 0.0004 = 0.02

  38. Since p + q = 1, then the frequency of p is • p=1 - q=1- 0.02 = 0.98 • In the Hardy-Weinberg equation, the frequency of heterozygotes is 2pq, • 2pq = 2(0.98)(0.02) = 0.04, or 4%, or 1/25 • Thus, heterozygotes for cystic fibrosis are rather common in the population (4%), even though the incidence of homozygous recessives is only 1/2500, or 0.04 percent.

  39. In general, the frequencies of all three genotypes can be estimated once the frequency of either allele is known and Hardy-Weinberg assumptions are invoked. The relationship between genotype and allele frequency is shown in Figure 22-6. • it is important to note that heterozygotes increase rapidly in a population as the values of p and q move from 0 or 1. This observation confirms our conclusion that when a recessive trait such as cystic fibrosis is rare, the majority of those carrying the allele are heterozygotes. In populations in which the frequencies of p and q are between 0.33 and 0.67, heterozygotes occur at higher frequency than either homozygote.

  40. 22.6 Factors That Alter AlleleFrequencies in Populations • We have noted that the Hardy-Weinberg law establishes an ideal population that allows us to estimate allele and genotype frequencies in populations in which the assumptions of random mating, absence of selection and mutation, and equal viability and fertility hold. Obviously, it is difficult to find natural populations in which all these assumptions hold. In nature, populations are dynamic, and changes in size and gene pool are common. The Hardy-Weinberg law allows us to investigate populations that vary from the ideal. In this and following sections, we discuss factors that prevent populations from reaching Hardy-Weinberg equilibrium, or that drive populations toward a different equilibrium, and the relative contribution of these factors to evolutionary change.

  41. 22.7 Natural Selection • The first assumption of the Hardy- Weinberg law is that individuals of all genotypes have equal rates of survival and equal reproductive success. If this assumption does not hold, allele frequencies may change from one generation to the next. To see why, let's imagine a population of 100 individuals in which the frequency of allele • A - 0.5 , a - 0.5. Assuming the previous generation mated randomly, the genotype frequencies • (0.5)2 - 0.25 for AA, 25 AA individuals • 2(0.5X0.5) = 0.5 for Aa, 50 Aa individuals • (0.5)2 = 0.25 for aa, 25 aa individuals.

  42. Now suppose that individuals with different genotypes have different rates of survival: All 25 AA individuals survive to reproduce, 90 percent or 45 of the Aa individuals 80 percent or 20 of the aa individuals • When the survivors reproduce, each contributes two gametes to the new gene pool, giving us 2(25) + 2(45) + 2(20) = 180 gametes. What are the frequencies of the two alleles in the surviving population? • 50 A gametes from AA + 45 A gametes from Aa, so the frequency of A is (50 + 45)/180 = 0.53. • Frequency of allele a is (45 + 40)/180 = 0.47. • Allele A has increased, while allele a has declined. • A difference among individuals in survival and/or reproduction rate is called natural selection. Natural selection is the principal force that shifts allele frequencies within large populations and is one of the most important factors in evolutionary change.

  43. Fitness and Selection Selection occurs whenever individuals type enjoy an advantage over other genotypes. However, selection may be weak or strong, depending on the magnitude of the advantage. In the example above, selection was strong. Weak selection might involve just a fraction of a percent difference in the survival rates of different genotypes. Advantages in survival and re­production ultimately translate into increased genetic contribution to future generations. An individual's genetic contribution to future generations is called fitness. Thus, genotypes associated with high rates of survival and/or high reproductive success are said to have high fitness, whereas genotypes associated with low rates of survival and/or low re­productive success are said to have low fitness.

  44. wAA for genotype AA, waa =1 wAafor genotype Aa, wAa =0.9 waa for aa. wafl= 0.8 \Let's consider selection against deleterious alleles. Fitness values wAA = 1, wAa = 1, and wbb= 0 describe a situation in which allele a is a lethal recessive. Homozygote recessive individuals die without leaving offspring, the frequency of allele awill decline. The decline in the frequency of allele a is described by the equation Qg= qo / 1-gqo

  45. intensity of selection

  46. The manner in which selection affects allele frequencies allows us to make some inferences about the CCK5-A32 allele A32/A32, 1/1 and 1/A32 current frequency of the A32 allele is 0.10. the genotype frequencies 0.81 for 1/1, 0.18 for 1/A32, and 0.01 for A32/A32. • Imagine also that 1 percent of the 1/1 and 1/A32 individuals in this population will contract HIV and die of AIDS. • fitness levels as follows: w1/1 = 0.99; w1/432 = 0.99; wA32/A32 = 1.0. Given the assigned fitness, we can predict that the frequency of the CCR5-A32 allele in the next generation will be 0.100091.

More Related