Environmental Tuning of Heritable Mutation Rates

Evolution, the fundamental strategy of life, is interplay of genetic variation and phenotypic selection. Mutations are the ultimate source of genetic variation, which are subsequently reshuffled by genetic recombination. Hence the relevance of the comprehension of molecular mechanisms that control mutation rates. Newly arisen mutations can have very different impacts on the fitness of the organism, ranging from deleterious through neutral to beneficial. Because the vast majority of mutations with observable effects are deleterious, selection acts to reduce mutation rates. Therefore, the rate of spontaneous mutations results from a balance between the effects of deleterious mutations and the physiological cost of reducing mutation rates. Organisms limit their mutation rates by diverse mechanisms: control over concentrations of endogenous and exogenous mutagens, pre-replication DNA repair systems, the insertion accuracy of polymerases, 3'-exonucleolytic proofreading, and post-replication systems mismatch repair systems. However, when adaptation is limited by the mutation supply rate, under some conditions, natural selection favors increased mutation rates by acting on allelic variation of the genetic systems that control fidelity of DNA replication and repair. Mutator alleles are carried to high frequency through hitchhiking with the adaptive mutations they generate. However, when fitness gain no longer counterbalances the fitness loss due to continuous generation of deleterious mutations, natural selection favors reduction of mutation rates. Evolutionary success of bacteria relies greatly on such constant fine-tuning of their mutation rates, which optimizes their adaptability to constantly changing environmental conditions.