Lecture 7: Introduction to Selection

1. Lecture 7: Introduction to Selection January 31, 2014

2. Last Time • Effects of inbreeding on heterozygosity and genetic diversity • Estimating inbreeding coefficients from pedigrees • Mixed mating systems • Inbreeding equilibrium • Introduction to selection

3. Today • Inbreeding and selection: inbreeding depression • The basic selection model • Dominance and selection

4. Offspring Heterozygosity Number of matings Parental Relatedness Relatedness Relatedness in Natural Populations • White-toothed shrew inbreeding (Crocidura russula) (Duarte et al. 2003, Evol. 57:638-645) • Breeding pairs defend territory • Some female offspring disperse away from parents • How much inbreeding occurs? • 12 microsatellite loci used to calculate relatedness in population and determine parentage • 17% of matings from inbreeding

5. What will be the long-term effects of inbreeding on this shrew population?

6. Inbreeding and allele frequency • Inbreeding alone does not alter allele frequencies • Yet in real populations, frequencies DO change when inbreeding occurs • What causes allele frequency change?

7. Natural Selection • Non-random and differential reproduction of genotypes • Preserve favorable variants • Exclude nonfavorable variants • Primary driving force behind adaptive evolution of quantitative traits

8. Fitness • Very specific meaning in evolutionary biology: • Relative competitive ability of a given genotype • Usually quantified as the average number of surviving progeny of one genotype compared to a competing genotype, or the relative contribution of one genotype to the next generation • Heritable variation is the primary focus • Extremely difficult to measure in practice. Often look at fitness components • Consider only survival, assume fecundity is equal

9. Number of heterozygous loci Inbreeding, Heterozygosity, and Fitness • Inbreeding reduces heterozygosity on genome-wide scale • Heterozygosity of individual can be index of extent of inbreeding • Multilocus Heterozygosity: • Proportion of loci for which individual is heterozygous • Often shows relationship with fitness Simulated Observed Correlation Between Heterozygosity and Fitness Deng and Fu 1998 Genetics 148:1333 Reed and Frankham 2003 Cons Biol 17:230

10. terrierman.com/inbredthinking.htm notexactlyrocketscience.wordpress.com wikipedia www.myrmecos.net/ Inbreeding Depression • Reduced fitness of inbred individuals compared to outcrossed individuals • Negative correlation between fitness and inbreeding coefficient observed in wide variety of organisms • Inbreeding depression often more prevalent under stressful conditions Lynch and Walsh 1998

11. Mechanisms of Inbreeding Depression • Two major hypotheses: Partial Dominance and Overdominance • Partial Dominance (really a misnomer) • Inbreeding depression is due to exposure of recessive deleterious alleles • Overdominance • Inherent advantage of heterozygosity • Enhanced fitness of heterozygote due to pleiotropy (one gene affects multiple traits): differentiation of allele functions • Bypass homeostasis/regulation

12. What about long-term effects on the shrew? • Fecundity (measured by number of offspring weaned) was not affected by relatedness between mating pairs or heterozygosity of individuals • No evidence of inbreeding depression in this species • Why not?

13. How do we quantify the effects of natural selection on allele frequencies over time?Can we predict and model evolution?

14. Relative Fitness of Diploids • Consider a population of newborns with variable survival among three genotypes: A1A1 A1A2 A2A2 N 100 100 100 Survival 80 56 40 • New parameter: ω, relative fitness (assuming equal fecundity of genotypes in this case) • Define ω=1 for best performer; others are ratios relative to best performer: Where N11s is number of A1A1 offspring surviving after selection in current generation And NM is the best-performing genotype

15. Average Fitness • Use genotype frequencies to calculate weighted fitness for entire population A1A1 A1A2 A2A2 ω1 0.7 0.5 ω = D(ω11) + H(ω12) + R(ω22) ω = (100/300)(1) + (100/300)(0.7) + (100/300)(0.5) = 0.733 • When fitness varies among genotypes, average fitness of the population is less than 1

16. Frequency After Selection = (0.33)(1)/0.733 = 0.45 D’ = D(ω11)/ω H’ = H(ω12)/ω = (0.33)(0.7)/0.733 = 0.32 R’ = R(ω22)/ω = (0.33)(0.5)/0.733 = 0.23 • Selection causes increase in more fit genotype and reduction in less fit genotypes • Allele Frequency Change: • q = (N22 + N12/2)/N = (100 + 100/2)/300 = 0.5 • q’ = (40+56/2)/176 = 0.39 • Δq = q’ – q = 0.39 – 0.5 = -0.11

17. Over time, what will happen to p and q in this population? What isΔp in the previous example?

18. Starting from Allele Frequencies q’ = q2ω22+pqω12 ω A1A1 A1A2 A2A2 freq0p2 2pqq2 ωω11ω12ω22 freq1p2ω11/ω 2pqω12/ω q2 ω22/ω ω = p2(ω11) + 2pq(ω12) + q2(ω22)

19. ω ω ω Simplifies to: Δq =pq[q(ω22- ω12) - p(ω11– ω12)] Change in Allele Frequencies due to Selection (i.e., evolution) q2ω22+pqω12 q2ω22+pqω12- qω q’ - q = - q = See p. 118 in your text for derivation “The single most important equation in all of population genetics and evolution!” Gillespie 2004, p. 62

20. ω Δq =pq[q(ω22 – ω12) - p(ω11- ω12)] Fitness effects of individual alleles • Effects of substituting one allele for another • Conceptually, compare fitness of homozygote to heterozygote • Rate of change inversely proportional to mean fitness of population: allele frequencies don’t change much in a fit population! • Marginal fitness: the effects of an individual allele on fitness (the average fitness genotypes containing that allele)

21. Incorporating Selection and Dominance • Selection Coefficient (s) • Measure of the relative fitness of one homozygote compared to another. • ω11 = 1 and ω22 = 1-s • s ranges 0 to 1 in most cases (more fit allele always A1 by convention) • Heterozygous Effect (level of dominance) (h) • Measure of the fitness of the heterozygote relative to the selective difference between homozygotes • ω12 = 1 - hs

22. Heterozygous Effect A1A1 A1A2 A2A2 Relative Fitness (ω) ω11ω12ω22 Relative Fitness (hs) 1 1-hs 1-s h = 0, A1 dominant, A2 recessive h = 1, A2 dominant, A1 recessive 0 < h < 1, incomplete dominance h = 0.5, additivity h < 0, overdominance h > 1, underdominance

23. Putting it all together ω Reduces to: Δq =pq[q(ω22 – ω12) - p(ω11- ω12)] Δq =-pqs[ph + q(1-h)] 1-2pqhs-q2s A1A1 A1A2 A2A2 Relative Fitness (ω) ω11ω12ω22 Relative Fitness (hs) 1 1-hs 1-s

24. ω ω ω Modes of Selection on Single Loci • Directional – One homozygous genotype has the highest fitness • Purifying selection AND Darwinian/positive/adaptive selection • Depends on your perspective! • 0 ≤ h ≤ 1 A1A1 A1A1 A1A1 A1A2 A1A2 A1A2 A2A2 A2A2 A2A2 • Overdominance – Heterozygous genotype has the highest fitness (balancing selection) • h<0, 1-hs > 1 • Underdominance– The heterozygous genotypes has the lowest fitness (diversifying selection) • h>1, (1-hs) < (1 – s) < 1 for s > 0

25. Directional Selection Δq =-pqs[ph + q(1-h)] 1-2pqhs-q2s 0 ≤ h ≤ 1 q Δq Time 0.5 1 0 q h=0.5, s=0.1

26. Lethal Recessives A1A1 A1A2 A2A2 A1A1 A1A2 A2A2 Relative Fitness (ω) ω11ω12ω22 Relative Fitness (hs) 1 1-hs 1-s • For completely recessive case, h=0 • What is s for lethal alleles? 1 0.8 0.6 ω 0.4 0.2 0 A1A1 A1A2 A2A2 A1A1 A1A2 A2A2