Selective strolls: fixation and extinction in diploids are slower for weakly selected mutations than for neutral ones

Abstract

In finite populations, an allele disappears or reaches fixation due to two main forces, selection and drift. Selection is generally thought to accelerate the process: a selected mutation will reach fixation faster than a neutral one, and a disadvantageous one will quickly disappear from the population. We show that even in simple diploid populations, this is often not true. Dominance and recessivity unexpectedly slow down the evolutionary process for weakly selected alleles. In particular, slightly advantageous dominant and mildly deleterious recessive mutations reach fixation more slowly than neutral ones. This phenomenon determines genetic signatures opposite to those expected under strong selection, such as increased instead of decreased genetic diversity around the selected site. Furthermore, we characterize a new phenomenon: mildly deleterious recessive alleles, thought to represent the vast majority of newly arising mutations, survive in a population longer than neutral ones, before getting lost. Hence, natural selection is less effective than previously thought in getting rid rapidly of slightly negative mutations, contributing their observed persistence in present populations. Consequently, low frequency slightly deleterious mutations are on average older than neutral ones.\n\nAuthor SummaryA common assumption among geneticists is that neutral alleles survive longer in a population than selected variants: negative selection would rapidly lead to the extinction of deleterious mutations, while advantageous alleles under positive selection will spread in the population till fixation. Here we show that unless an allele is perfectly codominant, these assumptions are often incorrect. Under weak selection, even in the simplest models, incomplete dominance and recessivity are sufficient to determine slower fixation and extinction times than for a neutral allele. These seemingly paradoxical results suggest that mildly deleterious mutations accumulate at the population level, and that nearly neutral mutations behave very differently from strongly selected ones. Furthermore, a fraction of selected regions would show opposite patterns for many standard statistics used to detect genomic signatures of positive selection, remaining virtually impossible to detect.