Is it ever possible that deviations from HWE are actually not a problem, but a signal of selection occurring for or against a phenotype? My intuition is that the kinds of timescales required to generate such a deviation would have to be so long that it’s unlikely, but curious if anyone has thoughts on this.
Hi Calen - interesting question! Here is a nice treatment of the impact of selection on the deviation from Hardy-Weinberg Equilibrium. In brief, the perturbation from selection under most regimes is quite subtle and sample sizes necessary to see such things are quite large!
The one place where things might be particularly apparent is in the circumstance where only one genotype (say the rare homozygote) has a strong selective effect and the other homozygote and heterozygote are neutral - under that circumstance variants can drift to be common-ish (say 1% minor allele frequency) but the rare homozygote is very rarely observed.