The role of transient hypermutators in adaptive mutation in Escherichia coli.
Microbial populations under nonlethal selection can give rise to mutations that relieve the selective pressure, a phenomenon that has come to be called "adaptive mutation." One explanation for adaptive mutation is that a small proportion of the cells experience a period of transient hypermutation, and that these hypermutators account for the mutations that appear. The experiments reported here investigated the contribution that hypermutators make to the mutations occurring in a Lac- strain of Escherichia coli during selection for lactose utilization. A broad mutational screen, loss of motility, was used to compare the frequency of nonselected mutations in starved Lac- cells, in Lac+ revertants, and in Lac+ revertants carrying yet another nonselected mutation. These frequencies allowed us to calculate that the hypermutating subpopulation makes up approximately 0.06% of the population and that its mutation rate is elevated approximately 200-fold. From these numbers we conclude that the hypermutators are responsible for nearly all multiple mutations but produce only approximately 10% of the adaptive Lac+ mutations.
Rosche
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WA
Department of Environmental Health, Boston University School of Public Health, Boston University School of Medicine, Boston, MA 02118, USA.
Foster
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PL
D004926:Escherichia coli / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D007763:Lac Operon; D009154:Mutation