THE ORIGIN OF ADAPTIVE MUTANTS - RANDOM OR NONRANDOM

Several recent reports have claimed that adaptive mutants in bacteria and yeast are induced by selective conditions. The results of these re ports suggest that mutants can arise nonrandomly with respect to fitne ss, contrary to what has been widely accepted. In several cases that h ave received careful experimental reexamination, however, the detectio n of seemingly nonrandom mutation has been explained as an experimenta l artifact. In the remaining cases, there is no evidence to suggest th at cells have the capacity to direct or choose which genetic variants will arise. Instead, current models propose processes by which genetic variants persist as mutations only if they enable cell growth and DNA replication. Most of these models are apparently contradicted by expe rimental data. One model, the hypermutable state model, has recently r eceived limited circumstantial support. However, in this model the ori gin of adaptive mutants is random; the apparent nonrandomness of mutat ion is merely a consequence of natural selection. The critical distinc tion between the origin of genetic variation (mutation) and the possib le consequence of that variation (selection) has been neglected by pro ponents of directed mutation.