The Balance Between Mutators and Nonmutators in Asexual Populations

Abstract

Mutator alleles, which elevate an individual’s mutation rate from 10 to 10,000-fold, have been found at high frequencies in many natural and ex- perimental populations. Mutators are continually produced from nonmu- tators, often due to mutations in mismatch-repair genes. These mutators gradually accumulate deleterious mutations, limiting their spread. How- ever, they can occasionally hitchhike to high frequencies with beneficial mutations. We study the interplay between these effects. We first analyze the dynamics of the balance between the production of mutator alleles and their elimination due to deleterious mutations. We find that when deleteri- ous mutation rates are high in mutators, there will often be many “young”, recently produced mutators in the population, and the fact that deleteri- ous mutations only gradually eliminate individuals from a population is important. We then consider how this mutator-nonmutator balance can be disrupted by beneficial mutations, and analyze the circumstances under which fixation of mutator alleles is likely. We find that dynamics is crucial: even in situations where selection on average acts against mutators, so they cannot stably invade, the mutators can still occasionally generate beneficial mutations and hence be important to the evolution of the population.