Dominance

1. Dominance • Refers to an allele’s phenotypic effect in the heterozygous condition • NOT its numerical prevalence • For example, a Dominant allele may be LESS common than a recessive allele!

2. Dominance • If the dominant and recessive alleles A and a (with freq. of p and q) are in H-W Equilibrium • The frequency of the dominant phenotype is p2 and 2pq • The frequency of the recessive phenotype is q2

3. Dominance – Moth Example • Black Phenotype (Dominant) = 10% • Grey Phenotype (Recessive) = 90% p=Black allele q=Grey allele • Assume this population H-W Equil. (Rounding) • q2 = 0.9  q = 0.95 (0.94868) • therefore  p = 0.05 (0.051316) • This implies that p2 = (0.05)2 = 0.0025 (0.0026334) • .25% are dominant homozygote • Heterozygotes = 2pq = 2(0.05)(0.95) = 0.095 0.095 (or 9.5%) are heterozygotes

4. Dominance • A dominant allele may well be less common than a recessive allele.

5. Estimating the Proportion of Polymorphic Loci • Why?  To know how much genetic variation exists within a population -Also, allows us to understand patterns of variation (as we will see in a few minutes...) • HOW?

6. Methods Used to Estimate Genetic Polymorphism • Protein electrophoresis • RFLP’s restriction fragment length polymorphisms • DNA Sequences • Microsatellites

7. Polymorphism of Adh

8. Polymorphism of Ldh

9. Variation at the DNA Level

10. Allelic diversity across loci • Heterozygosity or mean heterozygosity • As the avg. frequency of heterozygotes across loci • As the fraction of loci that are heterozygous in the genotype of the avg. individual. • % of polymorphic loci • Fraction of loci in a population that have multiple alleles.

11. Heterozygosity

12. Genetic variation at allozyme loci

13. How is polymorphism maintained? • Do forces of natural selection maintain these polymorphisms, or are they neutral, subject only to the operation of random genetic drift?

14. Multiple Loci • Genes do not exist in isolation • Multiple genes probably effect a single character • Physically associated on chromosome • Linkage disequilibrium

15. Evolution at Multiple Loci • We have considered the Hardy-Weinberg Equilibrium Principle for one locus at a time • Can this model be extended to a two or higher locus case? • Must make a more realistic model

16. Evolution at Two Loci • Consider two loci on the same chromosome: A and B • Alleles A and a; B and b • Track both allele frequencies and chromosome frequencies • Four possible chromosome genotypes: AB, Ab, aB, and ab • Haplotypes: multilocus genotype of a chromosome

17. Evolution at Two Loci • Loci are in linkage equilibrium if the frequency of one allele does not affect the frequency of the other • Linkage disequilibrium = locus frequencies affect each other • May affect evolution of each other by genetic linkage • Genes may be inherited as a group • May be based on physical distance between the loci

18. Evolution at Two Loci • Numerical example • Two hypothetical populations with 25 chromosomes each • We can calculate allele frequencies and chromosome frequencies

20. Evolution at Two Loci • Numerical example • Allele frequencies same for both populations • Chromosome frequencies differ slightly • To see difference, can calculate frequency of allele B on chromosomes carrying A versus frequency of chromosomes carrying a • Can depict this graphically

22. Evolution at Two Loci • Numerical example • Top population is in linkage equilibrium • Chromosome genotype of one locus is independent of other locus • Bottom population is in linkage disequilibrium • Nonrandom association between a genotype at one locus and another • If we know one genotype we have a clue about the other

24. Evolution at Two Loci • Conditions for Linkage Equilibrium • The frequency of B on chromosomes carrying A is equal to the frequency of B on chromosomes carrying a • The frequency of any chromosome haplotype can be calculated by multiplying frequencies of constituent alleles • The quantity D, the coefficient of linkage disequilibrium, is equal to zero • D = gABgab - gAbgaB • gs are frequencies of chromosomes

25. Evolution at Two Loci • Assess conditions for hypothetical example • Frequencies of chromosomes are equal • True for top, not for bottom • Frequencies of haplotypes can be calculated by multiplying allele frequencies • A X B = (0.6)(0.8) = 0.48 YES • A X B = (0.6)(0.8) = 0.48 NO AB = 0.44 • D = 0 • gABgab - gAbgaB = (0.48)(0.08) = (0.12)(0.32) YES • gABgab - gAbgaB = (0.44)(0.04) = (0.16)(0.36) NO

27. Evolution at Two Loci • If the population is in linkage equilibrium, Hardy-Weinberg equations can be used for each locus independently • Assume no selection, no mutation, no migration, infinite population, panmixia • What creates linkage disequilibrium? • Selection on multilocus genotypes • Genetic drift • Population admixture

28. Evolution at Two Loci • How to eliminate linkage disequilibrium • Sexual reproduction reduces linkage disequilibrium • Meiosis, crossing over, outbreeding • Meiosis breaks up old genotype combinations and creates new ones • Genetic Recombination • Randomizes genotypes of loci with respect to each other

29. Evolution at Two Loci • Why does linkage disequilibrium matter? • If two loci are in linkage disequilibrium, selection at one locus changes allele frequencies at the other • Cannot use Hardy-Weinberg to calculate allele or genotype frequencies • In practice the change in one locus due to linkage disequilibrium could erroneously be interpreted as selection on that locus

30. Evolution at Two Loci • Why does linkage disequilibrium matter? • If in linkage equilibrium Hardy-Weinberg can still be used • Random sexual reproduction is very efficient at eliminating linkage disequilibrium • Most loci are in linkage equilibrium • Empirical study of 5000 human loci found that only 4% were in linkage disequilibrium

31. Evolution at Two Loci • CCR5-D32 allele • Where did the allele come from? • Why is it mainly in Europe? • Stephens measured linkage disequilibrium in CCR5-D32 with two loci nearby on same chromosome • GAAT and AFMB • Neutral alleles • 192 Europeans • GAAT and AFMB are nearly in linkage equilibrium • CCR5-D32 in strong linkage disequilibrium with both

32. Evolution at Two Loci • CCR5-D32 allele • Linked alleles • + - 197 - 215 • How did linkage disequilibrium arise? • Selection, genetic drift, or population admixture • Not selection because GAAT and AFMB are selectively neutral • Not population admixture or the allele would be elsewhere in the world • Must be genetic drift

33. Evolution at Two Loci • CCR5-D32 allele • At some time in past only the wild type allele (+) existed • Then on the chromosome CCR5-GAAT-AFMB with alleles + - 197 - 215 a mutation occurred to D32 • Linkage is now breaking down • Some individuals with + - 197 - 217 are now found

34. Evolution at Two Loci • CCR5-D32 allele • Stephens used rates of crossing over and mutation to calculate how fast the linkage disequilibrium would be expected to break down • Used this calculation to estimate how long ago D32 appeared • This allele first appeared between 275 and 1875 years ago • Probably about 700 years ago

35. Evolution at Two Loci • CCR5-D32 allele • Unique mutation must have happened in Europe • Probably occurred elsewhere but was not favored by selection • Why was D32 favored in Europe? • Must have been strong selection to raise from nearly 0% to 20% in 700 years

36. Evolution at Two Loci • CCR5-D32 allele • Perhaps D32 provides protection from other diseases • It has been hypothesized that it protects against the bacterium Yersinia pestis, the pathogen that caused the Black Death • Investigations are being performed now to test this theory

37. Geographic Variation • Differences in phenotype (or genotype) among different geographic populations of the same species

38. Patterns of Geographic Variation • Sympatric Populations • (syn = “together”; patra = “fatherland”) • Overlapping ranges • Parapatric Populations • (para = “besides”) • adjacent but not overlapping ranges • e.g. High elevation and low elevation separate populations • Allopatric Populations • (allos = “other”) • non-overlapping

39. Rat Snakes (Elaphe obsoleta) Allopatric geographic variation

40. Molecular Phylogeny of Rat Snakes (Elaphe obsoleta)

41. Historical dispersal patterns in Rat Snakes (Elaphe obsoleta)

42. Genetic Distance • Quantify the degree of genetic differentiation among two or more populations of the same species, or among different species. • Nei’s D

43. Geographically Variable Characters • Morphological • Life history • Behavior • Ecology

44. Character Displacement • Sympatric populations of two species differ more than allopatric populations in their food use etc. these differences are generally reflected in morphology.

46. Conclusions about variation • A species is not genetically uniform over its geographic range • Some differences appear to be adaptive consequences • Genetic differences between populations are the same in kind as genetic differences among individuals within a pop.

47. Origin of Genetic Variation • Gene mutation – an alteration of the genetic (DNA) sequence • Mutations have evolutionary consequences only if they are transmitted to the next generation • Somatic cell • Germ line cell

48. Various types of mutations • Point mutations • Transition – substitution of a purine for a purine or a pyrimidine for pyrimidine (A G) or (C T) • Transversion – substitution of a purine for a pyrimidine or vice-versa (A T) or (A C) ... and so-on

49. Categories of Point Mutations • Synonymous • Change in DNA sequence  No Change in Amino Acid sequence • Non-Synonymous • Change in DNA sequence  Change in Amino Acid sequence

50. Synonymous VS. Nonsynonymous DNA1 = AAA GCT CAT GTA GAA DNA2 = AAT GCT GAT GTA GAA Protein1 = Lys Ala His Val Glu Protein2 = Lys Ala Asp Val Glu Synonymous mutation Nonsynonymous mutation