The evolution of mutation rates: separating causes from consequences

Natural selection can adjust the rate of mutation in a population by acting on allelic variation affecting processes of DNA replication and repair. Be cause 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 p henotypic effects are harmful, however, and thus there is relentless select ion within populations for lower genomic mutation rates. Selection on benef icial mutations can counter this effect by favoring alleles that raise the mutation rate, but the effect of beneficial mutations on the genomic mutati on rate is extremely sensitive to recombination and is unlikely to be impor tant in sexual populations. In contrast, high genomic mutation rates can ev olve in asexual populations under the influence of beneficial mutations, bu t this phenomenon is probably of limited adaptive significance and represen ts, 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 sett ing the genomic mutation rate in sexual and asexual systems, regardless of the benefits of mutation in producing new adaptive variation. Maintenance o f mutation rates higher than the minimum set by this "cost of fidelity" is likely only under special circumstances. (C) 2000 John Wiley & Sons, Inc.