Experimental evolution and the dynamics of genomic mutation rate modifiers

Abstract

Because genes that affect mutation rates are themselves subject to mutation, mutation rates can be influenced by natural selection and other evolutionary forces. The population genetics of mutation rate modifier alleles has been a subject of theoretical interest for many decades. Here, we review experimental contributions to our understanding of mutation rate modifier dynamics. Numerous evolution experiments have shown that mutator alleles (modifiers that elevate the genomic mutation rate) can readily rise to high frequencies via genetic hitchhiking in non-recombining microbial populations. Whereas these results certainly provide an explanatory framework for observations of sporadically high mutation rates in pathogenic microbes and in cancer lineages, it is nonetheless true that most natural populations have very low mutation rates. This raises the interesting question of how mutator hitchhiking is suppressed or its phenotypic effect reversed in natural populations. Very little experimental work has addressed this question; with this in mind, we identify some promising areas for future experimental investigation.

Figure 1

Mutator hitchhiking depends on the relative mutation supply rates to mutator and wild-type subpopulations. (a) When a mutator allele is rare, the subpopulation with the wild-type mutation rate can have a higher mutation supply rate than the mutator subpopulation and therefore will tend to acquire new beneficial mutations more quickly. This keeps the mutator from rising in frequency. (b) If sufficiently common, a mutator subpopulation can have a higher mutation supply rate than the wild type. Each new beneficial mutation then has a higher tendency to arise in association with the mutator, causing the mutator to hitchhike toward higher frequency.