Lecture 7: Introduction to Selection. September 14, 2012

Transcription

1 Lecture 7: Introduction to Selection September 14, 2012

2 Announcements Schedule of open computer lab hours on lab website No office hours for me week. Feel free to make an appointment for M-W. Guest lecture next Friday, September 21: Prof. Jennifer Hawkins, Transposable Elements Exam on September 26, Review session on Sept 24. Sample on schedule webpage.

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

4 Kinship Coefficient CA 1 CA 2 What would be the kinship coefficient of D and E? B C D E P k DE = f P = m i= N i (1 + f CA i )

5 Today Inbreeding and selection: inbreeding depression The basic selection model Dominance and selection

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

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

8 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?

9 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 Number of heterozygous loci Deng and Fu 1998 Genetics 148:1333 Correlation Between Heterozygosity and Fitness Reed and Frankham 2003 Cons Biol 17:230

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

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 Partial Dominance and Lethal Equivalents Lethal equivalents (B): the average number of deaths that would be caused by making all deleterious recessives homozygous Humans typically carry 4 or 5 lethal alleles and/or lethal eqivalents Lynch and Walsh 1998

13 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?

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

15 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

16 ω Relative Fitness of Diploids Consider a population of newborns with variable survival among three genotypes: A 1 A 1 A 1 A 2 A 2 A 2 N Survival 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: N11 s 80 N22s 40 N11 = = 100 N22 1 ω = = = 0.5 NMs 80 NMs 80 N 100 N = M M Where N 11S is number of A 1 A 1 offspring surviving after selection in current generation And N M is the best-performing genotype

17 Average Fitness Use genotype frequencies to calculate weighted fitness for entire population A 1 A 1 A 1 A 2 A 2 A 2 ω ω = D(ω 11 ) + H(ω 12 ) + R(ω 22 ) ω = (100/300)(1) + (100/300)(0.7) + (100/300)(0.5) = When fitness varies among genotypes, average fitness of the population is less than 1

18 Frequency After Selection D = D(ω 11 )/ω = (0.33)(1)/0.733 = 0.45 H = H(ω 12 )/ω = (0.33)(0.7)/0.733 = 0.32 R = R(ω 22 )/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 = (N 22 + N 12 /2)/N = ( /2)/300 = 0.5 q = (40+56/2)/176 = 0.39 Δq = q q = = -0.11

19 Over time, what will happen to p and q in this population? What is Δp in the previous example?

20 Starting from Allele Frequencies A 1 A 1 A 1 A 2 A 2 A 2 freq 0 p 2 2pq q 2 ω ω 11 ω 12 ω 22 freq 1 p 2 ω 11 /ω 2pq ω 12 /ω q 2 ω 22 /ω ω = p 2 (ω 11 ) + 2pq(ω 12 ) + q 2 (ω 22 ) q = q 2 ω 22 +pqω 12 ω

21 Change in Allele Frequencies due to Selection (i.e., evolution) Simplifies to: q - q = q 2 ω 22 +pqω 12 - qω ω Δq =pq[q(ω 22 - ω 12 ) - p(ω 11 ω 12 )] See math box 6.1 in text for derivation The single most important equation in all of population genetics and evolution! Gillespie 2004, p. 62 ω

22 Fitness effects of individual alleles Δq =pq[q(ω 22 ω 12 ) - p(ω 11 - ω 12 )] 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; see p. 191 of text) ω

23 New Parameters Selection Coefficient (s) Measure of the relative fitness of one homozygote compared to another. ω 11 = 1 and ω 22 = 1-s s ranges 0 to 1 in most cases (more fit allele always A 1 by convention) Heterozygous Effect (level of dominance) (h) Measure of the fitness of the heterozygote relative to the selective difference between homozygotes ω 12 = 1 - hs

24 Heterozygous Effect A 1 A 1 A 1 A 2 A 2 A 2 Relative Fitness (ω) ω 11 ω 12 ω 22 Relative Fitness (hs) 1 1-hs 1-s h = 0, A 1 dominant, A 2 recessive h = 1, A 2 dominant, A 1 recessive 0 < h < 1, incomplete dominance h = 0.5, additivity h < 0, overdominance h > 1, underdominance

25 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 ω AAA Aa aa 1 A 1 A 1 A 2 A 2 A 2 Overdominance Heterozygous genotype has the highest fitness (balancing selection) h<0, 1-hs > 1 ω AA Aa aa A 1 A 1 A 1 A 2 A 2 A 2 Underdominance The heterozygous genotypes has the lowest fitness (diversifying selection) h>1, (1-hs) < (1 s) < 1 for s > 0 ω AAA Aa aa 1 A 1 A 1 A 2 A 2 A 2