Genetic Linkage

1. Genetic Linkage

3. Two pops may have the same allele frequencies but different chromosome frequencies.

4. Conditions for Linkage Equilibrium (Two locus case) Frequency of B is the same on chromosome A and a Frequency of haplotypes AB, ab, Ab, aB can be calculated from allele frequencies A=p, a=q, B=t, and b=s. f(AB) = pt f(ab) = qs f(Ab) = ps f(aB) = pt 3) Coefficient of linkage disequilibrium (D) = 0 f(AB) x f(ab) - f(Ab) x f(aB) = D ps x qt - pt x qs = 0 (ranges from -0.25 to +0.25)

5. Hardy Weinberg Principle for Two Loci Chromosome frequencies remain unchanged across generations if loci are in linkage equilibria. If loci are in linkage disequilibria, the chromosome frequencies will move closer to linkage equilibrium each generation. What Creates Linkage Disequilibrium in a Population? selection, drift, and population admixture

6. Effects of Selection on Chromosome Frequencies ab/ab = body size of value 10 each additional A or B adds 1 value predators eat all individuals of size 12 or less 65.28% survive

7. Freq a = (0.1536 + 0.1536) / .6528)/2 = 0.24 Freq b = (0.0576 + 0.0576) / .6528)/2 = 0.09 Freq ab = .24 x .09 = .02 however! 65.28% survive Locus A and B are in disequilibrium among the survivors

8. Genetic Drift, followed by selection can cause linkage disequilibrium

9. Combination of Two Different Gene Pools Admixture

10. Recombination Breaks Down Linkage Disequilibria The rate of decline in LD increases with r

11. LD declines over time (rate depending on r) r = D sqrt(pqst)

13. A a B b A B b Law of Independent Assortment = 0.25 ab Meiosis All allele combinations in gametes equally probable = 0.25 aB a Concept of Linkage Ab = 0.25 AB = 0.25 Probability of recombination = 0.5 = 0.25 ab All allele combinations in gametes equally probable Meiosis = 0.25 aB Ab = 0.25 AB = 0.25

14. Probability of recombination = 0.3 = 0.35 ab A a Meiosis = 0.15 aB All allele combinations in gametes NOT equally probable b B Linked Loci Ab = 0.15 AB = 0.35 Probability of recombination = 0.1 = 0.45 ab A a b B Meiosis All allele combinations in gametes NOT equally probable = 0.05 aB Ab = 0.05 AB = 0.45

15. Concept: The closer two loci are on a chromosome, the lower the probability of recombination. Why important? (1) Affects rate that LD is broken down. (2) Allows one to determine the linear order of genes on a chromosome (make a genome map). (3) Maps allow for the localization of genes, mutant phenotypes, and QTL in the genome.

16. Selection at a single locus affects other loci under LD Selection has an effect on frequency of B alleles

17. LD among 1504 marker Loci on Human Chromosome 22. (Dawson et al. 2002)

18. Decay of LD Linkage Disequilibria Present level Time (generations)

19. How does LD help identify genes that may be under positive natural selection? For neutral alleles: Genetic drift is the primary evolutionary mechanism. So: If LD is detectable, indicates that an allele is young. Expect magnitude of LD is proportional to the age of an allele. If LD is not detectable, indicates that an allele is old. Expect old and frequent alleles, or old and rare alleles, But do not expect young, high frequency alleles. Indicates alleles at the locus may be under selection.

20. G6PD polymorphism and deficiency Countries with malaria have highest frequency of a reduced-activity allele.

21. Characterized SNPs for G6PD locus of 230 men Nine different G6PD alleles diagnosed by 11 SNPs Typed each allele for 14 SNPs outside the G6PD locus Sabeti et al., 2002

22. LD is higher for the G6PD-202A allele; suggests positive selection Probability that 2 randomly chosen “a” chromosomes have the same snps across a physical distance

23. The Evolutionary Biology of Sex There is Amazing Diversity in Reproductive Mode Kiwi Milk weed aphid

24. Blueheaded Wrasse

25. Sexual Reproduction Probably Evolved Early In Life Examples of parthenogenesis Dandelion Bdelloid rotifer Taraxacum officinale

26. What Mode of Reproduction is Better? An asexual female will have 2x as many grandchildren!

27. Why Aren’t All Species Asexual? Because asexual populations accumulate deleterious mutations Termed: Muller’s Rachet Possibly leads to extinction

28. Evidence for Muller’s Ratchet: Andersson and Hughes (1996) None of the 444 cultures had higher fitness than the wild type

29. Eichhornia paniculata Barrett and Charlesworth, (1991)

30. Flower number declined in a natural out crossing population, and heterosis was observed. Flower number stayed relatively constant in a naturally self-fertilizing population

31. Recombination Breaks the Ratchet Sex maybe advantageous because it can recreate favorable multilocus genotypes However, adaptation by this process is only faster in large populations

32. However, Suppression of Recombination is Important in the Evolution of Sex Chromosomes

33. Hypotheses for Short-Term Advantages of Sex • Recombination allows repair of damaged DNA • Genetically diverse progeny may outcompete asexual progeny • Muller’s ratchet • Deleterious mutations are more easily purged in sexual pops • Rate of evolution is higher in large sexual populations