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 mech-anism 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.

Spontaneous mutations in bacteria: chance or necessity?

“…Having done this, Cairns, Overbaugh and Miller were unable to detect significant yields of valine-resistant mutants. In addition to indicating that the amber mutation in the ZacZ gene was stable, the absence of Val' mutants was interpreted as demonstrating that new mutations arising under their conditions were confined to genes undergoing selection (see Cairns, Overbaugh & Miller, 1988;Foster, 1993). As noted elsewhere (MacPhee, 1994a), we believe that if Cairns, Overbaugh and Miller had used almost any carbon source other than glucose in these experiments, they would have observed very significant numbers of Val' mutants on their plates and hence would have been forced to adopt a totally different conclusion when assessing this portion of their original study (which presumably made an important contribution to their overall conclusion).…”

“…In this strain, a regulatory component of the arabinose operon (the araC gene) is placed upstream of the 1acZgene but separated from it by a short segment of the transposable phage Mu. Thus this E. coli strain has no functional lactose or arabinose operon, and is described as being Lac(Ara)- (Cairns, Overbaugh & Miller, 1988;Foster, 1993). However, if the phage segment is deleted, this strain is able to use lactose provided that arabinose is also present to induce transcription.…”

“…The hypermutable state model proposed by Hall (1990) is regarded by many as the most extreme version of the trial-and-error hypothesis proposed by Cairns, Overbaugh and Miller in their original 1988 paper (Foster, 1993). In this model, Hall (1990) suggests that during periods of prolonged starvation cells may enter a hypermutable state.…”

“…Thus suggestions by Lenski and his colleague(s) (and others) that many of the late-arising La& mutants may have had their origins in additional cell division of the parental (e.g. Lac-) bacteria tend to be countered by comments that the required numbers of cell divisions and corresponding increases in population numbers simply could not have taken place without having been noticed (Foster, 1993(Foster, , 1994; in this regard, we point out that although it may not have been made absolutely explicit, it has certainly been implied on a number of occasions by Foster and others (see for example Foster, 1993Foster, , 1994 that once mutations in excess of expectation on the basis of a generation-dependent mutation rate have been observed, it can safely be assumed that the additional ones are selection-induced, i.e. adaptive.…”

“…Observers of these non-random mutations have not yet reached a consensus over a suitable name for them, however. Thus although the mutations involved have often been referred to as 'directed' mutations, at other times they have been described as 'adaptive', 'CairnSian', 'selection-induced' or 'stationary phase' mutations depending upon the circumstances (Foster, 1993). In the present review, the term 'directed mutation' will be favoured in describing the putatively non-random mutants, primarily because this is the term which was originally used by Cairns, Overbaugh and Miller in their 1988 paper, but also because the use of this term implies that a novel molecular mechanism which is responsible for directing the production of these mutations must exist and hence should be amenable to detailed analysis.…”