Interference effects of deleterious and beneficial mutations in large asexual populations

Abstract

Linked beneficial and deleterious mutations are known to decrease the fixation probability of a favorable mutation in large asexual populations. While the hindering effect of strongly deleterious mutations on adaptive evolution has been well studied, how weakly deleterious mutations, either in isolation or with superior beneficial mutations, influence the rate of adaptation has not been fully explored. When the selection against the deleterious mutations is weak, the beneficial mutant can fix in many genetic backgrounds, besides the one it arose on. Here, taking this factor into account, I obtain an accurate analytical expression for the fixation probability of a beneficial mutant in an asexual population at mutation-selection balance. I then exploit this result along with clonal interference theory to investigate the joint effect of linked beneficial and deleterious mutations on the rate of adaptation, and identify parameter regions where it is reduced due to interference by either beneficial or deleterious or both types of mutations. I also study the evolution of mutation rates in adapting asexual populations, and find that linked beneficial mutations have a stronger influence than the deleterious mutations on mutator fixation.