title: Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation.
abstract: Stationary-phase mutation in microbes can produce selected ('adaptive') mutants preferentially. In one system, this occurs via a distinct, recombination-dependent mechanism. Two points of controversy have surrounded these adaptive reversions of an Escherichia coli lac mutation. First, are the mutations directed preferentially to the selected gene in a Lamarckian manner? Second, is the adaptive mutation mechanism specific to the F plasmid replicon carrying lac? We report that lac adaptive mutations are associated with hypermutation in unselected genes, in all replicons in the cell. The associated mutations have a similar sequence spectrum to the adaptive reversions. Thus, the adaptive mutagenesis mechanism is not directed to the lac genes, in a Lamarckian manner, nor to the F' replicon carrying lac. Hypermutation was not found in non-revertants exposed to selection. Therefore, the genome-wide hypermutation underlying adaptive mutation occurs in a differentiated subpopulation. The existence of mutable subpopulations in non-growing cells is important in bacterial evolution and could be relevant to the somatic mutations that give rise to cancers in multicellular organisms.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Torkelson
authors.forename: R S
authors.initials: RS
authors.lastname: Harris
authors.forename: M J
authors.initials: MJ
authors.lastname: Lombardo
authors.forename: J
authors.initials: J
authors.lastname: Nagendran
authors.forename: C
authors.initials: C
authors.lastname: Thulin
authors.forename: S M
authors.initials: SM
authors.lastname: Rosenberg
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D001483:Base Sequence; D005075:Biological Evolution; D002876:Chromosomes, Bacterial; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development; D005144:F Factor / Q000235:genetics; D016680:Genome, Bacterial; D007763:Lac Operon / Q000235:genetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011995:Recombination, Genetic; D012641:Selection, Genetic; D013997:Time Factors