Selection and Plasmid Transfer Underlie Adaptive Mutation in Escherichia coli

In the Cairns-Foster adaptive mutation system, a +1 frameshift mutant of is plated on lactose medium, where the nondividing population gives rise to Lac revertant colonies during a week under selection. Reversion requires the mutant allele to be located on a conjugative F' plasmid that also encodes the error-prone DNA polymerase, DinB. Rare plated cells with multiple copies of the mutant F' plasmid initiate the clones that develop into revertants under selection. These initiator cells arise before plating, and their extra copies allow them to divide on lactose and produce identical F' -bearing daughter cells that can mate with each other. DNA breaks can form during plasmid transfer and their recombinational repair can initiate rolling-circle replication of the recipient plasmid. This replication is mutagenic because the amplified plasmid encodes the error-prone DinB polymerase. A new model proposes that Lac revertants arise during mutagenic over-replication of the F' plasmid under selection. This mutagenesis is focused on the plasmid because the cell chromosome replicates very little. The outer membrane protein OmpA is essential for reversion under selection. OmpA helps cells conserve energy and may stabilize the long-term mating pairs that produce revertants.