Population genetics and Hardy–Weinberg reasoning

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Calculate allele and genotype frequencies first, then decide what the population model can—and cannot—tell you about evolutionary mechanism.

About 17 minutes, including the population-count example and checks.

Separate allele frequency from genotype frequency

Population genetics counts alleles and genotypes at different levels. In a diploid population with alleles A and a, the genotype frequencies are the proportions of AA, Aa, and aa individuals. The allele frequencies count copies: each AA individual contributes two A alleles, each heterozygote contributes one A and one a, and each aa individual contributes two a alleles.

If the frequency of A is p and the frequency of a is q, then p + q = 1 for a two-allele locus. Do not jump to p², 2pq, and q² until the problem either states Hardy–Weinberg conditions or asks you to calculate the genotype proportions expected under that model.

Concept: Hardy–Weinberg is a model, not a force

Under the classic Hardy–Weinberg model for a diploid locus, allele frequencies remain constant and genotype frequencies follow p² + 2pq + q² = 1 when the relevant assumptions are met. Those assumptions are typically idealized as a very large population, random mating with respect to the locus, no selection, no migration, and no mutation affecting the allele frequencies of interest.²

The model is a reference expectation, not a process pushing populations toward equilibrium. Selection, migration, mutation, genetic drift, nonrandom mating, population structure, or even genotyping problems can produce departures from an expected Hardy–Weinberg pattern. The observation of a departure is therefore evidence that the simple model is not fully describing the data—not a diagnosis of one particular cause.²

Worked application: start from genotype counts

An original population contains 1,000 diploid individuals at locus A:

The population contains 2,000 allele copies. The number of A alleles is 2(360) + 480 = 1,200, so:

p = f(A) = 1200/2000 = 0.60.

The number of a alleles is 2(160) + 480 = 800, so:

q = f(a) = 800/2000 = 0.40.

If Hardy–Weinberg genotype proportions are expected from those allele frequencies, then:

• AA: p² = 0.60² = 0.36
• Aa: 2pq = 2(0.60)(0.40) = 0.48
• aa: q² = 0.40² = 0.16

Those expected proportions match the observed proportions exactly in this constructed dataset. That agreement means the counts are consistent with the Hardy–Weinberg expectation. It does not prove that no evolutionary process has ever acted on the population, nor does it prove each idealized assumption by direct observation.

Pattern: a founder sample can change frequency by sampling

Now suppose 50 individuals establish a geographically isolated colony. Their genotype counts are 10 AA, 20 Aa, and 20 aa. The new colony has 100 allele copies. Its A count is 2(10) + 20 = 40, so p = 0.40; its a count is 60, so q = 0.60.

This frequency shift is compatible with a founder effect: a small subgroup can carry only a fraction of the allele distribution present in the larger source population.³ But be careful about the causal claim. If the problem merely gives two populations with different frequencies and no history, the difference alone does not establish founder effect. Here, the founding event and small sample are explicitly supplied.

Small populations are also more vulnerable to random allele-frequency changes across generations because sampling variance is larger. That process is genetic drift. Drift is non-directional with respect to fitness: a variant can rise or fall by chance. Selection, by contrast, changes expected reproductive contribution when genotypes differ in survival or reproductive success under the relevant environment.

Rule: a deviation does not identify its cause

Suppose a population has p = 0.70 and q = 0.30. Under Hardy–Weinberg expectations, the heterozygote frequency is 2pq = 0.42. If only 0.30 of the observed individuals are heterozygous, the data depart from that expectation. But several mechanisms could generate such a pattern. Nonrandom mating or inbreeding can reduce heterozygosity while leaving allele frequencies initially unchanged. Population substructure can also create a heterozygote deficit when distinct subpopulations are pooled.

Likewise, a change in allele frequency between generations does not identify whether selection, migration, drift, or mutation caused it. To distinguish mechanisms, ask what additional evidence each explanation predicts: differential reproductive success supports selection; movement of individuals or gametes supports migration; a small bottleneck with stochastic changes supports drift; direct sequence emergence can support mutation.

The MCAT reasoning move is therefore two-stage: calculate what changed, then ask what evidence identifies why it changed.

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Sources

1. AAMC. Content Category 1C.
2. NCBI Bookshelf. Methods Guide for Medical Test Reviews: Hardy–Weinberg Equilibrium.
3. NCBI MeSH. Founder Effect.