Population Genetics I. Basic Principles A. Definitions: B. Basic computations:

1. Population Genetics I. Basic Principles A. Definitions: B. Basic computations: C. Hardy-Weinberg Equilibrium: D. Utility 1. If no real populations can explicitly meet these assumptions, how can the model be useful? It is useful for creating an expected model that real populations can be compared against to see which assumption is most likely being violated. 2. Also, If HWCE is assumed and the frequency of homozygous recessives can be measured, then the number of heterozygous carriers can be estimated.

2. Example: Cystic fibrosis (cc) has a frequency of 1/2500 = 0.0004 in people of northern European ancestry. More than 1,000 different mutations in the CFTR gene have been identified in cystic fibrosis patients. The most common mutation (observed in 70% of cystic fibrosis patients) is a three-base deletion in the DNA sequence, causing an absence of a single amino acid in the protein. = 0.0004 x 0.7 = 0.00028 Water follows salt flow by osmosis and dilutes mucus

3. Example: Cystic fibrosis (cc) has a frequency of 1/2500 = 0.0004 in people of northern European ancestry; common allele = 0.00028. Mucus in lungs reduces respiration, increases bacterial infection In pancreas/liver, reduces flow/efficacy of digestive enzymes In intestine, reduces nutrient uptake

4. Example: Cystic fibrosis (cc) has a frequency of 1/2500 = 0.0004 in people of northern European ancestry, common allele = 0.00028 How many carriers are there? q2 = 0.00028, so q2 = q = 0.017. p + q = 1, so p = 0.983 So, the frequency of heterozygous carriers for this allele = 2pq = 0.033 This calculation can only be performed if HWE is assumed.

5. Population Genetics I. Basic Principles II. Deviations from HWE A. Mutation

6. II. Deviations from HWE A. Mutation 1. Basics:

7. II. Deviations from HWE A. Mutation 1. Basics: a. Consider a population with: f(A) = p = .6 f(a) = q = .4

8. II. Deviations from HWE A. Mutation 1. Basics: a. Consider a population with: f(A) = p = .6 f(a) = q = .4 b. Suppose ‘A' mutates to ‘a' at a realistic rate of: μ = 1 x 10-5

9. II. Deviations from HWE A. Mutation 1. Basics: a. Consider a population with: f(A) = p = .6 f(a) = q = .4 b. Suppose ‘A' mutates to ‘a' at a realistic rate of: μ = 1 x 10-5 c. Well, what fraction of alleles will change? ‘A' will decline by: μp = .6 x 0.00001 = 0.000006 ‘a' will increase by the same amount.

10. II. Deviations from HWE A. Mutation 1. Basics: a. Consider a population with: f(A) = p = .6 f(a) = q = .4 b. Suppose ‘A' mutates to ‘a' at a realistic rate of: μ = 1 x 10-5 c. Well, what fraction of alleles will change? ‘A' will decline by: μp= .6 x 0.00001 = 0.000006 ‘a' will increase by the same amount. d. So, the new gene frequencies will be: q1 = q + μp = .400006 p1 = p - μp = p(1-μ) = .599994

11. At this realistic rate, it takes thousands of generations to cause appreciable change. Mutation is the source of new alleles, but it does not change the frequency of alleles very much. Were the mutationists wrong?

12. II. Deviations from HWE A. Mutation 1. Basics: 2. Other Considerations:

13. II. Deviations from HWE A. Mutation 1. Basics: 2. Other Considerations: - Selection: Selection can BALANCE mutation... so a deleterious allele might not accumulate as rapidly as mutation would predict, because it is eliminated from the population by selection each generation.

14. II. Deviations from HWE A. Mutation 1. Basics: 2. Other Considerations: - Selection: - Drift: The probability that a new allele (produced by mutation) becomes fixed (q = 1.0) in a population = 1/2N (basically, it's frequency in that population of diploids). In a small population, this chance becomes measureable and likely. So, NEUTRAL mutations have a reasonable change of becoming fixed in small populations... and then replaced by new mutations.

15. II. Deviations from HWE A. Mutation B. Migration 1. Basics: - Consider two populations: p2 = 0.7 q2 = 0.3 p1 = 0.2 q1 = 0.8

16. II. Deviations from HWE A. Mutation B. Migration 1. Basics: - Consider two populations: p2 = 0.7 q2 = 0.3 p1 = 0.2 q1 = 0.8 suppose migrants immigrate at a rate such that the new immigrants represent 10% of the new population

17. II. Deviations from HWE A. Mutation B. Migration 1. Basics: - Consider two populations: p2 = 0.7 q2 = 0.3 p1 = 0.2 q1 = 0.8 suppose migrants immigrate at a rate such that the new immigrants represent 10% of the new population

18. II. Deviations from HWE A. Mutation B. Migration 1. Basics: - Consider two populations: IMPORTANT EFFECT, BUT MAKES POPULATIONS SIMILAR AND INHIBITS DIVERGENCE AND ADAPTATION TO LOCAL CONDITIONS (EXCEPT IT MAY INTRODUCE NEW ADAPTIVE ALLELES) p2 = 0.7 q2 = 0.3 p1 = 0.2 q1 = 0.8 suppose migrants immigrate at a rate such that the new immigrants represent 10% of the new population p(new) = p1(1-m) + p2(m) P(new) = (0.2).9 + (0.7)0.1 = 0.25

19. Frequency of the ‘B’ allele of the ABO blood group locus, largely as a result of the Mongol migrations following the fall of the Roman Empire

20. II. Deviations from HWE A. Mutation B. Migration C. Non-Random Mating 1. Positive Assortative Mating "like phenotype mates with like phenotype"

21. II. Deviations from HWE A. Mutation B. Migration C. Non-Random Mating 1. Positive Assortative Mating "like phenotype mates with like phenotype" a. Pattern:

22. II. Deviations from HWE A. Mutation B. Migration C. Non-Random Mating 1. Positive Assortative Mating "like phenotype mates with like phenotype" a. Pattern:

23. II. Deviations from HWE A. Mutation B. Migration C. Non-Random Mating 1. Positive Assortative Mating "like phenotype mates with like phenotype" a. Pattern:

24. a. Pattern: b. Effect: - reduction in heterozygosity at this locus; increase in homozygosity.

25. Groth, J. 1993. Call matching and positive assortative mating in Red Crossbills. The Auk 110L: 398-401. male female

26. Type 2 Type 1

27. II. Deviations from HWE A. Mutation B. Migration C. Non-Random Mating 1. Positive Assortative Mating 2. Inbreeding - reduction of heterozygosity across the entire genome, at a rate that correlates with the degree of relatedness. - full sibs, parent/offspring: lose 25%of heterozygosity each generation.

28. White tigers in the U.S. are all descendants of a brother-sister pair from the Cincinnati Zoo. The AZA has outlawed captive breeding of white tigers. BigCatRescue

29. II. Deviations from HWE A. Mutation B. Migration C. Non-Random Mating 1. Positive Assortative Mating 2. Inbreeding - reduction of heterozygosity across the entire genome, at a rate that correlates with the degree of relatedness. - full sibs, parent/offspring: lose 50%of heterozygosity each generation. CAN INCREASE PROBABILITY OF DIVERGENCE BETWEEN POPULATIONS, AND CAN ALSO BE A WAY TO PURGE DELETERIOUS ALLELES (ALTHOUGH AT A COST TO REPRODUCTIVE OUTPUT).

30. II. Deviations from HWE A. Mutation B. Migration C. Non-Random Mating D. Genetic Drift - Sampling Error 1. The organisms that actually reproduce in a population may not be representative of the genetics structure of the population; they may vary just due to sampling error (chance).

31. D. Genetic Drift - Sampling Error 1. The organisms that actually reproduce in a population may not be representative of the genetics structure of the population; they may vary just due to sampling error (chance). - most dramatic in small samples. 2. effects:

32. D. Genetic Drift - Sampling Error 1. The organisms that actually reproduce in a population may not be representative of the genetics structure of the population; they may vary just due to sampling error (chance). - most dramatic in small samples. 2. effects: 1 - small pops will differ more, just by chance, from the original population

33. D. Genetic Drift - Sampling Error 1. The organisms that actually reproduce in a population may not be representative of the genetics structure of the population; they may vary just due to sampling error (chance). - most dramatic in small samples. 2. effects: 1 - small pops will differ more, just by chance, from the original population 2 - small pops will vary more from one another than large populations

34. D. Genetic Drift - Sampling Error 1. most dramatic in small samples. 2. effects 3. circumstances when drift is very important:

35. D. Genetic Drift - Sampling Error 1. most dramatic in small samples. 2. effects 3. circumstances when drift is very important: - “Founder Effect” The Amish, a very small, close-knit group decended from an intial population of founders, has a high incidence of genetic abnormalities such as polydactyly

36. - “Founder Effect” and Huntington’s Chorea HC is a neurodegenerative disorder caused by an autosomal lethal dominant allele. The fishing villages around Lake Maracaibo in Venezuela have the highest incidence of Huntington’s Chorea in the world, approaching 50% in some communities.

37. - “Founder Effect” and Huntington’s Chorea HC is a neurodegenerative disorder caused by an autosomal lethal dominant allele. The fishing villages around Lake Maracaibo in Venezuela have the highest incidence of Huntington’s Chorea in the world, approaching 50% in some communities. The gene was mapped to chromosome 4, and found the HC allele was caused by a repeated sequence of over 35 “CAG’s”. Dr. Nancy Wexler found homozygotes in Maracaibo and described it as the first truly dominant human disease (most are incompletely dominant and cause death in the homozygous condition).

38. - “Founder Effect” and Huntington’s Chorea HC is a neurodegenerative disorder caused by an autosomal lethal dominant allele. The fishing villages around Lake Maracaibo in Venezuela have the highest incidence of Huntington’s Chorea in the world, approaching 50% in some communities. By comparing pedigrees, she traced the incidence to a single woman who lived 200 years ago. When the population was small, she had 10 children who survived and reproduced. Folks with HC now trace their ancestry to this lineage. Also a nice example of “coalescence” – convergence of alleles on a common ancestral allele.

39. D. Genetic Drift - Sampling Error 1. most dramatic in small samples. 2. effects 3. circumstances when drift is very important: - “Founder Effect” - “Bottleneck”

40. - “Genetic Bottleneck” If a population crashes (perhaps as the result of a plague) there will be both selection and drift. There will be selection for those resistant to the disease (and correlated selection for genes close to the genes conferring resistance), but there will also be drift at other loci simply by reducing the size of the breeding population. Cheetah have very low genetic diversity, suggesting a severe bottleneck in the past. They can even exchange skin grafts without rejection. European Bison, hunted to 12 individuals, now number over 1000. Fell to 100’s in the 1800s, now in the 100,000’s

41. II. Deviations from HWE A. Mutation B. Migration C. Non-Random Mating D. Genetic Drift - Sampling Error E. Selection