The evolution of mutation rates: separating causes from consequences

Abstract

Natural selection can adjust the rate of mutation in a population by acting on allelic variation affecting processes of DNA replication and repair. Because mutation is the ultimate source of the genetic variation required for adaptation, it can be appealing to suppose that the genomic mutation rate is adjusted to a level that best promotes adaptation. Most mutations with phenotypic effects are harmful, however, and thus there is relentless selection within populations for lower genomic mutation rates. Selection on beneficial mutations can counter this effect by favoring alleles that raise the mutation rate, but the effect of beneficial mutations on the genomic mutation rate is extremely sensitive to recombination and is unlikely to be important in sexual populations. In contrast, high genomic mutation rates can evolve in asexual populations under the influence of beneficial mutations, but this phenomenon is probably of limited adaptive significance and represents, at best, a temporary reprieve from the continual selection pressure to reduce mutation. The physiological cost of reducing mutation below the low level observed in most populations may be the most important factor in setting the genomic mutation rate in sexual and asexual systems, regardless of the benefits of mutation in producing new adaptive variation. Maintenance of mutation rates higher than the minimum set by this "cost of fidelity" is likely only under special circumstances.

Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy

“…Underlying the hallmarks of cancers is genome instability, which can generate genetic diversity 7. Genetic alterations can potentially upset the balance between proto‐oncogenes and tumour suppressor genes, leading to tumorigenesis.…”

Scaling laws in bacterial genomes: A side-effect of selection of mutational robustness?

“…Moreover, the variability level can influence the survival of lineages: those with inappropriate levels of variability can go to extinction due to a lack of robustness or evolvability -defined as the capacity of a lineage to generate adaptive heritable genotypic and phenotypic variation (Nehaniv, 2005). Thus there can be an indirect selective pressure on the factors that control the mutational variability of the phenotype: the mutation rate (Sniegowski et al, 2000), but also the properties of the genotype-phenotype map like modularity (Wagner and Altenberg, 1996).…”

Sexual selection and the evolution of evolvability

“…This is because, notwithstanding the finding that the optimum mutation rate may be higher (Leigh, 1973), selection will tend to drive the mutation rate downwards (Metzgar and Wills, 2000;Sniegowski et al, 2000). Nevertheless, recent work has highlighted modifiers of the mutation rate, in particular mutator genes, which were originally identified in bacteria (Cox, 1976).…”