A population genetics study finds fewer heterozygotes than Hardy-Weinberg equilibrium predicts at a particular locus in a rural village. Which explanation is most consistent with this finding?
AStrong selection in favor of heterozygotes is operating, since heterozygotes have higher fitness
BInbreeding or population substructure (Wahlund effect) may be reducing heterozygosity below the random-mating expectation
CThe allele frequencies have been changing rapidly, proving that directional selection is occurring
DGenetic drift is currently operating, as drift always produces homozygote excess
A deficit of heterozygotes relative to HWE expectations (homozygote excess) is the signature of inbreeding or population substructure. In the Wahlund effect, combining samples from genetically distinct subpopulations that each have their own allele frequencies creates an apparent homozygote excess in the pooled sample. Option (a) is backwards — heterozygote advantage produces more heterozygotes than expected, not fewer. Option (d) is wrong because drift can shift allele frequencies in any direction; it does not predictably produce homozygote excess.
Question 2 Multiple Choice
In genome-wide association studies (GWAS), SNPs that strongly deviate from Hardy-Weinberg equilibrium in control samples are often excluded. What is the primary reason?
ASuch SNPs are located in genes under strong selection, which would confound disease association tests
BA large HWE deviation in healthy controls most likely indicates a genotyping error, since strong biological departures from equilibrium are rare in large control samples
CHWE-violating SNPs always result from population stratification and require separate statistical models
DSNPs violating HWE cannot have their allele frequencies accurately estimated
In a large, reasonably random control sample, genuine biological forces strong enough to cause massive HWE deviation are rare. A dramatic excess of one homozygote is far more likely to reflect a genotyping artifact — where one allele is systematically miscalled — than a biological process. Excluding these SNPs improves data quality. Option (a) is possible but not the primary reason for routine exclusion; option (c) overstates the case.
Question 3 True / False
Hardy-Weinberg equilibrium is reached after just one generation of random mating, regardless of the initial genotype frequencies.
TTrue
FFalse
Answer: True
This is one of the most surprising and non-obvious results in population genetics. No matter what the starting genotype frequencies are (as long as allele frequencies are fixed), a single generation of random mating produces genotype frequencies of p², 2pq, and q². Students commonly assume equilibration requires many generations, analogizing to reaching a physical or thermal equilibrium. The single-generation result follows from the algebra of random union of gametes.
Question 4 True / False
Hardy-Weinberg equilibrium is most useful as a description of real populations, which typically satisfy its assumptions of no selection, mutation, migration, or drift.
TTrue
FFalse
Answer: False
Real populations virtually never simultaneously satisfy all HWE assumptions. HWE is useful precisely as a null model — a baseline expectation against which real populations are compared. Its value comes from detecting and interpreting deviations, not from describing actual equilibrium. Deviations reveal which forces are operating: inbreeding, selection, drift, or migration. A framework's utility as a diagnostic tool does not require real systems to match it.
Question 5 Short Answer
What does a positive inbreeding coefficient F indicate, and how is it derived from Hardy-Weinberg expectations?
Think about your answer, then reveal below.
Model answer: A positive F indicates that observed heterozygosity is lower than Hardy-Weinberg expectations — individuals in the population share more recent ancestry (are more related) than random mating would produce. F is calculated as F = 1 − (observed heterozygosity / expected heterozygosity), where expected heterozygosity is 2pq from allele frequencies assuming HWE. If F = 0, the population matches HWE. If F > 0, there is a proportional reduction in heterozygosity consistent with inbreeding or population substructure.
F-statistics extend this logic hierarchically: FIS measures inbreeding within subpopulations, FST measures genetic differentiation among subpopulations, and FIT measures inbreeding relative to the total population. All are grounded in comparing observed heterozygosity to HWE-expected heterozygosity at different levels. The HWE null model is thus not just a population description — it is the mathematical foundation for all F-statistic-based inference about population structure.