Two steps forward, one step back: the pleiotropic effects of favoured alleles.

Pleiotropy is one of the most commonly observed attributes of genes. Yet the extent and influence of pleiotropy have been underexplored in population genetics models. In this paper, I quantify the extent to which pleiotropy inhibits the spread of alleles in response to directional selection on a focal trait. Under the assumption that pleiotropic effects are extensive and deleterious, the fraction of alleles that are beneficial overall is severely limited by pleiotropy and rises nearly linearly with the strength of directional selection on the focal trait. Over a broad class of distribution of pleiotropic effects, the mean selective effect of those alleles that are beneficial overall is halved, on average, by pleiotropy. The fraction of new mutant alleles that are beneficial overall and that succeed in fixing within a population is even more severely limited when directional selection is weak, but it rises quadratically with the strength of directional selection. Finally, the mean selective effect of mutant alleles that are beneficial and succeed in fixing is reduced by one-third, on average, by pleiotropy. These results help to shape our understanding of the evolutionary inertia caused by pleiotropy.