title: Evolution of Mutation Rates in Rapidly Adapting Asexual Populations.
abstract: Mutator and antimutator alleles often arise and spread in both natural microbial populations and laboratory evolution experiments. The evolutionary dynamics of these mutation rate modifiers are determined by indirect selection on linked beneficial and deleterious mutations. These indirect selection pressures have been the focus of much earlier theoretical and empirical work, but we still have a limited analytical understanding of how the interplay between hitchhiking and deleterious load influences the fates of modifier alleles. Our understanding is particularly limited when clonal interference is common, which is the regime of primary interest in laboratory microbial evolution experiments. Here, we calculate the fixation probability of a mutator or antimutator allele in a rapidly adapting asexual population, and we show how this quantity depends on the population size, the beneficial and deleterious mutation rates, and the strength of a typical driver mutation. In the absence of deleterious mutations, we find that clonal interference enhances the fixation probability of mutators, even as they provide a diminishing benefit to the overall rate of adaptation. When deleterious mutations are included, natural selection pushes the population toward a stable mutation rate that can be suboptimal for the adaptation of the population as a whole. The approach to this stable mutation rate is not necessarily monotonic: even in the absence of epistasis, selection can favor mutator and antimutator alleles that "overshoot" the stable mutation rate by substantial amounts.
authors.affiliation: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138.|Department of Physics, Harvard University, Cambridge, Massachusetts 02138.|Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Good
authors.affiliation: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138 mdesai@oeb.harvard.edu.|Department of Physics, Harvard University, Cambridge, Massachusetts 02138.|Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Desai
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D019143:Evolution, Molecular; D006238:Haploidy; D008957:Models, Genetic; D059645:Mutation Rate; D012100:Reproduction, Asexual / Q000235:genetics*; D012641:Selection, Genetic
keywords: antimutator; deleterious load; hitchhiking; mutator