One-locus diploid model Goals: Predict the outcome of selection: when will it result in fixation, when in polymorphism Understand the effect of dominance on the rate of evolution

Back to the Foré GenotypeMMMVVV juvenile adult If selection continues to act in the same way, what will be the outcome?

One-locus diploid model Selection acts in the diploid phase random mating, no migration, and no mutation large population

Model conditions :allele frequencies initial genotype frequencies After selection? p[t] q[t] p[t] q[t]

Genotype frequencies after selection f’(AA) f’(Aa) f’(aa)

Allele frequencies after selection f’(A) = f’(a) = f’(AA) = f’(Aa) = f’(aa) = 100% 50%

One-locus diploid model p(t+1) = p(t) 2 W AA + p(t)q(t)W aa p(t) 2 W AA + 2p(t)q(t)W Aa + q(t) 2 W aa

One-locus diploid model Forms of selection Directional Selection: Favoring allele A Favoring allele a Heterozygote advantage Heterozygote disadvantage (Which forms of selection were present in the haploid selection model?)

Directional selection

Directional selection: terms W AA = 1 W Aa = 1 + hs W aa = 1 + s s: h:

Dominance

Imagine two alleles fighting over the phenotype (in this case, fitness(: where does the heterozygote end up? W AA 1 W aa 1 + s W Aa 1 + s/2

Dominance Imagine two alleles fighting over the phenotype (in this case, fitness(: where does the heterozygote end up? W AA 1 W aa 1 + s W Aa =

Dominance Imagine two alleles fighting over the phenotype (in this case, fitness(: where does the heterozygote end up? W AA 1 W aa 1 + s W Aa 1 + hs

Dominance Imagine two alleles fighting over the phenotype (in this case, fitness(: where does the heterozygote end up? W AA 1 W aa 1 + s W Aa 1 + hs

Dominance Imagine two alleles fighting over the phenotype (in this case, fitness(: where does the heterozygote end up? W AA = 1 W aa 1 + s W Aa

Dominance example Sickle cell anemia: HH = healthy red blood cells Hh = sickle cell trait hh = sickle cell anemia Describe the dominance of H for: blood oxygen capacity? malaria resistance?

Dominance and selection p(t+1) = p(t) 2 W AA + p(t)q(t)W Aa p(t) 2 W AA + 2p(t)q(t)W Aa + q(t) 2 W aa If A is dominant and rare: If A is dominant and common:

Selection against a common allele If W AA < W Aa < W aa, selection favors the a allele

Heterozygote advantage W Aa > W aa ; W Aa > W AA W Aa = 1; W aa = 0.9; W AA = 0.8

Heterozygote disadvantage W Aa < W aa ; W Aa < W AA W Aa = 0.9; W aa = 1.0; W AA = 0.95

Equilibria What are the equilibria?

Behaviour at polymorphic equilibrium

One-locus diploid model Examples: Sickle-cell anemia

One-locus diploid model Examples: Sickle-cell anemia For the Nigerian population studied: W HH = 0.88 W Hh = 1 W hh = 0.14 What is the expected equilibrium frequency of the non-mutant allele (H)?

Readings and questions References: Mead, S., M. P. H. Stumpf, et al Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science 300: Reading: Freeman and Herron, chapter 6 (chapter 5) Questions: 1.What are the relative fitnesses for the three Foré genotypes? (Use the juvenile data to estimate genotype frequencies prior to selection). What is the expected outcome of selection? Explain. 2.Imagine that a population experienced malaria but lacked the sickle-cell allele. Using the Nigerian fitness data, sketch the evolution of the population if a new sickle cell mutation arose in the population. 3.You have identified a locus that influences survival in sparrows. The relative fitnesses for each genotype are: W AA = 1.0; W Aa = 0.9; W aa = 0.6. Describe the relationship between the two alleles in terms of dominance.