1. Lecture 8: Types of Selection February 5, 2014

2. Last Time uIntroduction to selection uPredicting allele frequency change in response to selection

3. Today uDominance and types of selection  Why do lethal recessives stick around? uEquilibrium under selection  Stable equilibrium: overdominance  Unstable equilibrium: underdominance

4. Lethal Recessives uFor completely recessive case, h=0 uFor lethality, s=1 ω A1A1A1A1 A1A2A1A2 A2A2A2A2 0 0.2 0.4 0.6 0.8 1 A1A1A1A1 A1A2A1A2 A2A2A2A2 A1A1A1A1 A1A2A1A2 A2A2A2A2 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

5. Lethal Recessive For q<1 uh=0; s=1 uω 11 =1; ω 12 =1-hs=1; ω 22 =1-s=0 uΔq more negative at large q uPopulation moves toward maximum fitness uRate of change decreases at low q Δq = -pqs[ph + q(1-h)] 1-2pqhs-q 2 s -pq 2 1-q 2 = -q 2 1+q =

6. Retention of Lethal Recessives uAs p approaches 1, rate of change decreases uVery difficult to eliminate A 2, recessive deleterious allele from population  Heterozygotes “hidden” from selection (ω 11 =1; ω 12 =1-hs=1)  At low frequencies, most A 2 are in heterozygous state: q p 2q 2 2pq = q p q 0.5 0.1 0.01 1 9 99 Ratio of A2 alleles in heterozygotes versus homozygotes

7. Time to reduce lethal recessives It takes a very large number of generations to reduce lethal recessive frequency once frequency gets low See Hedrick 2011, p. 123 for derivation

8. Selection against Recessives uFor completely recessive case, h=0 uFor deleterious recessives, s<1 A 1 A 1 A 1 A 2 A 2 A 2 ωω 11 ω 12 ω 22 s1 1-hs 1-s ω A1A1A1A1 A1A2A1A2 A2A2A2A2 0 0.2 0.4 0.6 0.8 1 A1A1A1A1 A1A2A1A2 A2A2A2A2 A1A1A1A1 A1A2A1A2 A2A2A2A2

9. Selection Against Recessives uh=0; 0<s<1 uMaximum rate of change at intermediate allele frequencies uLocation of maximum depends on s: q ≈ 2/3 for small s uWhere is maximum rate of change in q for lethal recessive? uWhat is final value of q? uWhat is final average fitness of population? Δq = -pqs[ph + q(1-h)] 1-2pqhs-q 2 s -pq 2 s 1-q 2 s = -q 2 s(1-q) 1-q 2 s = s=0.2 s=0.4 s=0.2 s=0.4 s=1 Lethal recessive, continues off chart

10. Modes of Selection on Single Loci uDirectional – One homozygous genotype has the highest fitness  Purifying selection AND Darwinian/positive/adaptive selection  Depends on your perspective!  0 ≤ h ≤ 1 uOverdominance – Heterozygous genotype has the highest fitness (balancing selection) h 1 uUnderdominance – The heterozygous genotypes has the lowest fitness (diversifying selection) h>1, (1-hs) 0 ω A1A1A1A1 A1A2A1A2 A2A2A2A2 ω A1A1A1A1 A1A2A1A2 A2A2A2A2 ω A1A1A1A1 A1A2A1A2 A2A2A2A2

11. Equilibrium uThe point at which allele frequencies become constant through time uTwo types of equilibria  Stable  Unstable uThe question: stable or unstable?  What happens if I move q a little bit away from equilibrium?

12. Stable Equilibria railslide.com Perturbations from equilibrium cause variable to move toward equilibrium

13. Unstable Equilibria Perturbations from equilibrium cause variable to move away from equilibrium

14. Heterozygote Advantage (Overdominance) uNew notation for simplicity (hopefully): Genotype A1A1A1A1 A1A2A1A2 A2A2A2A2 Fitnessω 11 ω 12 ω 22 Fitness in terms of s and h1 – s 1 11 – s 2 ω A1A1A1A1 A1A2A1A2 A2A2A2A2

15. Equilibrium under Overdominance uEquilibrium occurs under three conditions: q=0, q=1 (trivial), and s 1 p – s 2 q = 0

16. Equilibrium under Overdominance uAllele frequency always approaches same value of q when perturbed away from equilibrium value uStable equilibrium uAllele frequency change moves population toward maximum average fitness