title: Fitness evolution and the rise of mutator alleles in experimental Escherichia coli populations.
abstract: We studied the evolution of high mutation rates and the evolution of fitness in three experimental populations of Escherichia coli adapting to a glucose-limited environment. We identified the mutations responsible for the high mutation rates and show that their rate of substitution in all three populations was too rapid to be accounted for simply by genetic drift. In two of the populations, large gains in fitness relative to the ancestor occurred as the mutator alleles rose to fixation, strongly supporting the conclusion that mutator alleles fixed by hitchhiking with beneficial mutations at other loci. In one population, no significant gain in fitness relative to the ancestor occurred in the population as a whole while the mutator allele rose to fixation, but a substantial and significant gain in fitness occurred in the mutator subpopulation as the mutator neared fixation. The spread of the mutator allele from rarity to fixation took >1000 generations in each population. We show that simultaneous adaptive gains in both the mutator and wild-type subpopulations (clonal interference) retarded the mutator fixation in at least one of the populations. We found little evidence that the evolution of high mutation rates accelerated adaptation in these populations.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Shaver
authors.forename: Peter G
authors.initials: PG
authors.lastname: Dombrowski
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Sweeney
authors.forename: Tania
authors.initials: T
authors.lastname: Treis
authors.forename: Renata M
authors.initials: RM
authors.lastname: Zappala
authors.forename: Paul D
authors.initials: PD
authors.lastname: Sniegowski
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D001426:Bacterial Proteins; D020137:Base Pair Mismatch; D005075:Biological Evolution; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein; D009154:Mutation; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C074770:MutL protein, E coli; D000251:Adenosine Triphosphatases; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli