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 ≈0.06% of the population and that its mutation rate is elevated ≈200-fold. From these numbers we conclude that the hypermutators are responsible for nearly all multiple mutations but produce only ≈10% of the adaptive Lac(+) mutations.