Selection mode governs the scaling of genetic load, diversity, and adaptation

Abstract

Nearly neutral theory predicts that deleterious alleles can behave approximately neutrally when selection is weak relative to genetic drift. For codominant mutations, the conventional nearly neutral threshold is |s| {approx} 1/(2Ne); thus, when Ne = 500, a mutation with |s| = 0.001 lies at this threshold. For strongly recessive mutations, however, newly arisen copies occur mainly in heterozygotes, so selection is much weaker while they are rare. We used forward-time simulations to test whether competitive soft selection can purge strongly recessive deleterious mutations that behave as nearly neutral under hard selection. The focal mutations had s = -0.001 and h = 0.01, placing their effect when rare about 50-fold below the corresponding nearly neutral threshold. Under hard selection, these mutations behaved almost neutrally, continuing to accumulate, with some reaching fixation. Under rank-based soft selection, accumulation was strongly suppressed; at high fecundity, mutations remained at low frequency and none reached fixation. Purging strengthened as more candidates competed for a fixed number of recruitment opportunities. A pairwise tournament produced the same qualitative but slightly weaker pattern. Thus, competitive soft selection can purge rare, recessive deleterious mutations whose effects fall well below the nearly neutral threshold under hard selection. By acting on aggregate multilocus fitness differences, relative competition may reduce genetic load and susceptibility to inbreeding depression. These findings are also relevant to genic capture, whereby many weak effects of deleterious mutations contribute to genome-wide genetic quality that can be exposed through competition and sexual selection.