Population Genetics and Evolution

1. Population Genetics and Evolution Mr. NicholsPHHS

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5. The Population as a Genetic Reservoir • Humans are not distributed randomly across the world, but are clustered into discrete populations

6. Populations • Populations • Local groups of organisms belonging to a single species, sharing a common gene pool • Populations can be described by age structure, geography, birth and death rates, and allele frequencies

7. Population Diversity • Populations are more diverse than individuals • Only a group can carry all the alleles for traits such as blood types A, B, AB, and O • All the alleles in a population are the gene pool • Gene pool • The set of genetic information carried by the members of a sexually reproducing population

8. Allele Frequency • Allele frequency • The frequency with which alleles of a particular gene are present in a population • The frequency of alleles in a population may change from generation to generation • Changes in allele frequency can cause change in phenotype frequency; long-term change in allele frequency is evolutionary change

9. How Can We Measure Allele Frequencies in Populations? • Population genetics studies allele frequencies in populations, not offspring of single matings • In some cases allele frequency in a population can be measured directly • In other cases, the Hardy-Weinberg Law is used to estimate allele frequencies within populations

10. Codominant Allele FrequenciesCan Be Measured Directly • Codominant allele frequencies can be measured directly by counting phenotypes • Phenotypes are equivalent to genotypes • Example: The MN blood group • LM and LN alleles are codominant and produce three phenotypes, M, N, and MN

11. Recessive Allele Frequencies Cannot Be Measured Directly • With recessive alleles, there is no direct relationship between phenotype and genotype • Heterozygotes and dominant homozygotes have the same phenotype • Hardy and Weinberg independently developed a mathematical formula to determine frequency of alleles when one or more alleles are recessive • Under certain specified conditions

12. The Hardy-Weinberg Law Measures Allele and Genotype Frequencies • Hardy-Weinberg Law • Allele and genotype frequencies remain constant from generation to generation when the population meets certain assumptions • There is a difference between how a trait is inherited and the frequency of recessive and dominant alleles in a population

13. Brachydactyly: A Dominant Trait • What is the relationship between allele frequency and phenotype frequency?

14. Assumptions of the Hardy-Weinberg Law • The population is large enough that there are no errors in measuring allele frequencies • All genotypes are equally able to reproduce • Mating in the population is random • Other factors that change allele frequency (mutation and migration) can be ignored

15. Mathematics ofthe Hardy-Weinberg Law • For a population, p + q = 1 • p = frequency of the dominant allele A • q = frequency of the recessive allele a • The chance of a fertilized egg carrying the same alleles is p2 (AA) or q2 (aa) • The chance of a fertilized egg carrying different alleles is pq (Aa)

16. Determining the Frequency ofAlleles in a New Generation • Depends on the frequency of dominant and recessive alleles in the parental generation

17. The Hardy-Weinberg Equation p2 + 2pq + q2 = 1 • 1 = 100% of genotypes in the new generation • p2 and q2 are the frequencies of homozygous dominant and recessive genotypes • 2pq is the frequency of the heterozygous genotype in the population

18. Calculating Frequency of Alleles in a New Generation • Given alleles in the parental generation are a (q = 0.4) and A (p = 0.6)

19. Populations Can Be in Genetic Equilibrium • Genetic equilibrium • When the allele frequency for a particular gene remains constant from generation to generation • Equilibrium in a population explains why dominant alleles do not replace recessive alleles • In equilibrium populations, Hardy-Weinberg law can be used to measure allele and genotype frequencies from generation to generation

20. Keep In Mind • The frequency of recessive alleles in a population cannot be measured directly

21. Using the Hardy-Weinberg Law in Human Genetics • The Hardy-Weinberg Law can be used to • Estimate frequencies of autosomal dominant and recessive alleles in a population • Detect when allele frequencies are shifting in a population (evolutionary change) • Measure the frequency of heterozygous carriers of deleterious recessive alleles in a population

22. Calculating the Frequency of Autosomal Dominant and Recessive Alleles • Count the frequency of individuals in the population with the recessive phenotype, which is also the homozygous recessive genotype (aa) • The frequency of genotype aa = q2 • The frequency of the a allele is √q2 = q • The frequency of the dominant allele (A) is calculated p = 1 - q

23. Calculating the Frequency of Alleles for X-Linked Traits • For X-linked traits, females (XX) carry 2/3 of the alleles and males (XY) carry 1/3 of the alleles • The number of males with the mutant phenotype equals the allele frequency for the recessive trait • Frequency of an X-linked trait in males is q • Frequency of the trait in females is q2

24. Calculating the Frequency of Multiple Alleles • In ABO blood types, six different genotypes are possible (AA, AO, BB, BO, AB, OO) • Allele frequencies: p (A) + q (B) + r (O) = 1 • Genotype frequencies: (p + q + r)2 = 1 • Expanded Hardy-Weinberg equation: • p2 (AA) + 2pq (AB) + 2pr (AO) + q2 (BB) + 2qr (BO) + r2 (OO) = 1

25. Frequencies of Heterozygotes • For a genetic disorder inherited as a recessive trait, most disease-causing alleles are carried by heterozygotes • The frequency of heterozygous carriers of deleterious recessive alleles in a population is used to calculate risk of having an affected child

26. Estimating the Frequency of Heterozygotes in a Population • Count the number of homozygous individuals in the population (q2) and calculate the frequency of the recessive allele q • Calculate the frequency of the dominant allele p (p = 1- q) • Calculate the frequency for the heterozygote genotype 2pq

27. Relationship between Allelic Frequency and Genotype Frequency • What are the chances of two heterozygotes mating and having a child with a recessive trait? • If 1 in 10,000 members of the population have the disorder, then 1 in 50 is a heterozygote • Chance of two mating is 1/50 x 1/50 = 1/2,500 • Chance of a given child being affected is ¼ • Chance of mating and having an affected child is 1/2,500 x ¼ = 1/10,000

28. Keep In Mind • Estimating the frequency of heterozygotes in a population is an important part of genetic counseling

29. Measuring Genetic Diversity in Human Populations • Human populations carry a large amount of genetic diversity • Mutation generates new alleles, but has little impact on allele frequency • If the mutation rate for a gene is known, the change in allele frequency resulting from new mutations in each generation can be calculated

30. Replacement of a Recessive Allele by Mutation Alone • Mutation alone has a minimal impact on the genetic variability present in a population

31. Genetic Drift Can Change Allele Frequencies • Forces such as genetic drift act on the genetic variation in the gene pool to change the frequency of alleles in the population • Genetic drift • Random fluctuations of allele frequencies from generation to generation that take place in small, isolated populations such as island populations or socioreligious groups

32. Founder Effects • Occasionally, populations start with a small number of individuals (founders) • Founder effects • Allele frequencies established by chance in a population that is started by a small number of individuals (perhaps only a fertilized female)

33. Tristan da Cuhna • An island population founded by a single family

34. Tristan da Cuhna • Residents of the island of Tristan da Cuhna are an example of isolation and inbreeding • Show increased homozygosity for recessive traits such as clinodactyly • Clinodactyly • An autosomal dominant trait that produces a bent finger

35. Selection • Wallace and Darwin identified selection as the primary force that leads to evolutionary divergence and the formation of new species • Selection increases the reproductive success of fitter genotypes

36. Natural Selection Acts on Variation in Populations • Natural selection acts on genetic diversity in populations and is the major force in driving evolution • Natural selection • Differential reproduction shown by some members of a population that is the result of differences in fitness

37. Fitness • Better-adapted individuals have an increased chance of leaving more offspring • Fitness • A measure of the relative survival and reproductive success of a specific individual or genotype

38. The Relationship between Sickle-Cell Anemia and Malaria • The allele for sickle-cell anemia is present in very high frequencies in certain populations • Many recessive homozygotes die in childhood • The sickle-cell allele confers resistance to the parasite Plasmodium, which causes malaria • Selection favors survival and differential reproduction of heterozygotes

39. Keep In Mind • Mutation generates all new alleles, but drift, migration, and selection determine the frequency of alleles in a population

40. Natural Selection Affects the Frequency of Genetic Disorders • Rare lethal or deleterious recessive alleles survive because the vast majority of them are carried in the heterozygous condition • Other factors can cause differential distribution of alleles in the human population • Migration, founder effects, mutations, selection

41. Lethal Alleles • Almost all individuals with Duchenne muscular dystrophy (DMD) die before reproducing • The mutation rate for DMD is high, introducing more DMD alleles • The frequency of the DMD allele in a population is balanced between alleles introduced by mutation and those removed by deaths

42. Heterozygote Advantage • The high frequency of genetic disorders in some populations is the result of selection that often confers increased fitness on heterozygotes • A single sickle-cell allele confers resistance to malaria • A single Tay-Sachs allele confers resistance to tuberculosis

43. Genetics in Society: Lactose Intolerance and Culture • The enzyme lactase converts lactose (milk sugar) into glucose and galactose • Lactase production slows or stops after childhood • Some populations have a gene for adult lactose metabolism (LA) • The cultural practice of keeping dairy herds was a selective factor that provided an advantage for the LA genotype

44. Keep In Mind • Survival and differential reproduction are the basis of natural selection

45. Genetic Variation in Human Populations • The biological concept of race changed from an emphasis on phenotypic differences to an emphasis on genotypic differences • Mutation introduces genetic variation • Natural selection and drift are the primary mechanisms that spread alleles through local population groups

46. How Can We Measure Gene Flow Between Populations? • Gene flow between populations is used to reconstruct the origin and history of populations • Example: Gene flow into the American black population from Europeans • West African populations have blood group FY*O • Europeans have blood groups FY*A and FY*B • In northern US cities, about 20% of genes in the black population are derived from Europeans

47. Are There Human Races? • Studies of variations in proteins, microsatellites, and nuclear genes show more genetic variation within populations than between populations • Conclusion: There is no clear genetic basis for dividing our species into races