Adaptive mutation in Escherichia coli strain FC40

Mutations can arise in static populations of cells that are subjected to no nlethal selective pressure, a phenomenon that has been called 'adaptive mut ation'. This phenomenon has been extensively studied in FC40, a strain of E scherichia coli that cannot metabolize lactose (Lac(-)) but that reverts to lactose utilization (Lac(+)) when lactose is its sole energy and carbon so urce. The adaptive Lac(+) mutations arise by two mutational processes: a re combination-dependent process that is highly active on the episome carrying the Lac(-) allele, and an unknown process that affects the whole genome. M ost of the Lac(+) mutations are due to the first process, which also produc es nonselected mutations on the F' episome. However, about 10% of the Lac() mutations arise in a subpopulation of cells that experience a period of t ransient hypermutation. Although minor contributors to any one type of muta tion, the hypermutators account for nearly all cases of multiple mutations. The evolutionary implications of these results are: (i) DNA synthesis asso ciated with recombination may be an important source of spontaneous mutatio n, particularly in cells that are not actively growing; (ii) the efficient mutational mechanism that occurs on the episome could result in the horizon tal transfer of new alleles among species that carry and exchange conjugal plasmids; and (iii) a subpopulation of transient hypermutators could be a s ource of multiple mutations that would allow for rapid adaptive evolution u nder adverse conditions.