Adaptive mutation: the uses of adversity

Abstract

When populations of microorganisms are subjected to certain nonlethal selections, useful mutants arise among the nongrowing cells whereas useless mutants do not. This phenomenon, known as adaptive, directed, or selection-induced mutation, challenges the long-held belief that mutations only arise at random and without regard for utility. In recent years a growing number of studies have examined adaptive mutation in both bacteria and yeast. Although conflicts and controversies remain, the weight of the evidence indicates that adaptive mutation cannot be explained by trivial artifacts and that nondividing cells accumulate mutations in the absence of genomic replication. Because this process tends to produce only useful mutations, the cells appear to have a mechanism for preventing useless genetic changes from occurring or for eliminating them after they occur. The model that most readily explains the evidence is that cells under stress produce genetic variants continuously and at random, but these variants are immortalized as mutations only if they allow the cell to grow.