In a malaria-endemic region, HbA/HbS heterozygotes have higher fitness than either HbA/HbA or HbS/HbS homozygotes. As the HbS allele becomes very common in the population, what happens to its fitness advantage?
AIt increases — more HbS alleles means more heterozygotes, amplifying the advantage
BIt stays constant — heterozygote advantage is independent of allele frequency
CIt decreases — as HbS becomes common, most HbS alleles end up in HbS/HbS homozygotes (low fitness), eroding the advantage
DThe HbS allele rapidly goes to fixation because selection always favors the fitter allele
This is the self-stabilizing logic of overdominance. When HbS is rare, nearly every HbS allele is paired with an HbA allele in a heterozygote — high fitness. As HbS becomes common, increasingly many HbS alleles end up in HbS/HbS homozygotes, which suffer from sickle-cell disease. Selection now acts against HbS. The same logic applies symmetrically to HbA: rare HbA alleles enjoy the heterozygote advantage, but common HbA alleles accumulate in lower-fitness HbA/HbA homozygotes. Neither allele can spread to fixation because its fitness declines as it becomes common — producing a stable equilibrium where both persist.
Question 2 Multiple Choice
In a prey species with two color morphs, predators form search images for the most common morph, making it easier to catch. Which type of balancing selection is operating, and what is its predicted outcome?
AOverdominance — heterozygotes carrying both color genes have higher survival
BDirectional selection — one morph will eventually be favored and reach fixation
CNegative frequency-dependent selection — the rare morph has higher fitness because predators focus on the common one, maintaining both morphs at equilibrium
DGenetic drift — random fluctuations maintain both morphs equally
Negative frequency-dependent selection means fitness is negatively correlated with frequency: when your morph is common, predators target you; when it's rare, they overlook you. This creates a self-correcting dynamic. If one morph becomes too common, selection favors the rare alternative, which then increases in frequency until it faces the same disadvantage. The result is a stable equilibrium where both morphs coexist at predictable frequencies — neither can be driven to fixation. This mechanism is thought to maintain MHC diversity in immune systems, where rare alleles confer resistance to pathogens that have evolved to evade common immune responses.
Question 3 True / False
Natural selection typically reduces genetic variation within a population by spreading the fittest allele and eliminating less fit alternatives.
TTrue
FFalse
Answer: False
Directional selection does reduce variation, but balancing selection is a counterexample that actively maintains it. Under overdominance, neither homozygote is fittest — only the heterozygote — so neither allele can reach fixation. Under negative frequency-dependent selection, rare alleles gain a fitness advantage precisely because they are rare, preventing elimination. The result is that variation is preserved rather than eroded. This is not a trivial exception: many medically and ecologically important polymorphisms (sickle-cell trait, MHC alleles, ABO blood groups) persist in populations because balancing selection maintains them against the erosive forces of drift and directional selection.
Question 4 True / False
Regions of the genome under balancing selection are expected to show unusually high heterozygosity and an excess of intermediate-frequency alleles compared to neutral regions of the genome.
TTrue
FFalse
Answer: True
These are the molecular signatures of balancing selection. Under neutral evolution, alleles drift toward high or low frequencies, producing a distribution skewed toward rare alleles (Tajima's D ≈ 0 or negative). Balancing selection keeps alleles near intermediate frequencies — the stable equilibria it maintains — producing elevated heterozygosity and a positive Tajima's D. Allelic lineages also persist much longer than expected under drift, giving unusually deep genealogies. The HLA (MHC) loci in humans, for example, show trans-species polymorphisms — alleles shared with other primates for millions of years — a signature impossible under neutral evolution or directional selection.
Question 5 Short Answer
Explain why overdominance (heterozygote advantage) produces a stable equilibrium where both alleles persist rather than one allele eventually driving the other to fixation.
Think about your answer, then reveal below.
Model answer: Overdominance creates a fitness landscape where the heterozygote Aa outperforms both homozygotes AA and aa. As a result, each allele has frequency-dependent fitness: when allele A is common, most A-bearing individuals are AA (low fitness), so selection acts against A. When A is rare, most A-bearing individuals are Aa (high fitness), so selection favors A. The same negative frequency dependence applies to allele a. Each allele is favored when rare and disfavored when common, producing a stable equilibrium frequency where both alleles persist indefinitely. At this equilibrium, the marginal fitness of each allele (averaged over all genotypes it appears in) is equal. Any perturbation from this equilibrium is corrected by selection, making it a stable attractor rather than a transient state.