Evidence that stationary-phase hypermutation in the Escherichia coli chromosome is promoted by recombination

Adaptive (or stationary-phase) mutation is a group of phenomena in which mu tations appear to occur more often when selected than when not. They may re present cellular responses to the environment in which the genome is altere d to allow survival. The best-characterized assay system and mechanism is r eversion of a Iac allele on an F' sex plasmid in Escherichia coli, in which the stationary-phase mutability requires homologous recombination function s. A key issue has concerned whether the recombination-dependent mutation m echanism is F' specific or is general. Hypermutation of chromosomal genes o ccurs in association with adaptive Lac(+) mutation. Here we present evidenc e that the chromosomal hypermutation is promoted by recombination. Hyperrec ombinagenic recD cells show elevated chromosomal hypermutation. Further, re cG mutation, which promotes accumulation of recombination intermediates pro posed to prime replication and mutation, also stimulates chromosomal hyperm utation. The coincident mutations at lac (on the F') and chromosomal genes behave as independent events, whereas coincident mutations at lac and other F-linked sites do not. This implies that transient covalent linkage of F' and chromosomal DNA (Hfr formation) does not underlie chromosomal mutation. The data suggest that recombinational stationary-phase mutation occurs in the bacterial chromosome and thus can be a general strategy for programmed genetic change.