Impact of fluctuating selection on genetic variation when new mutations are expected to be deleterious

Current research continues to debate the influence of fluctuating selection on genetic diversity within populations. In most previous models of fluctuating selection for studying genetic diversity, the distribution of selection coefficients is assumed to be symmetrical, meaning that the chances of having positive and negative selection coefficients are identical over time. These models predict that selective fluctuations reduce genetic diversity similar to the stochastic influence of genetic drift. Using stochastic simulations and analytical approaches based on diffusion approximations, we analyze the impact of fluctuating selection on genetic diversity when the distribution of selection coefficients over time is not symmetric, but is instead shifted to negative values. This captures the fact that new mutations are more likely to be deleterious. We show that, unlike the symmetric case, selective fluctuations can greatly increase genetic variation when new mutations are deleterious on average. We show that this phenomenon occurs because deleterious mutations that would be kept at low frequency in constant environment are able to transiently attain high frequencies in a changing environment. Our findings suggest that fluctuating selection could be an important force for generating genetic diversity even if it does not lead to long-term coexistence of alternate alleles.