title: Mutation rate dynamics in a bacterial population reflect tension between adaptation and genetic load.
abstract: Mutations are the ultimate source of heritable variation for evolution. Understanding how mutation rates themselves evolve is thus essential for quantitatively understanding many evolutionary processes. According to theory, mutation rates should be minimized for well-adapted populations living in stable environments, whereas hypermutators may evolve if conditions change. However, the long-term fate of hypermutators is unknown. Using a phylogenomic approach, we found that an adapting Escherichia coli population that first evolved a mutT hypermutator phenotype was later invaded by two independent lineages with mutY mutations that reduced genome-wide mutation rates. Applying neutral theory to synonymous substitutions, we dated the emergence of these mutations and inferred that the mutT mutation increased the point-mutation rate by ∼150-fold, whereas the mutY mutations reduced the rate by ∼40-60%, with a corresponding decrease in the genetic load. Thus, the long-term fate of the hypermutators was governed by the selective advantage arising from a reduced mutation rate as the potential for further adaptation declined.
authors.affiliation: Laboratoire Adaptation et Pathogénie des Micro-Organismes,  Université Joseph Fourier Grenoble, F-38042 Grenoble Cedex 9,  France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Wielgoss
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Barrick
authors.forename: Olivier
authors.initials: O
authors.lastname: Tenaillon
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wiser
authors.forename: W James
authors.initials: WJ
authors.lastname: Dittmar
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cruveiller
authors.forename: Béatrice
authors.initials: B
authors.lastname: Chane-Woon-Ming
authors.forename: Claudine
authors.initials: C
authors.lastname: Médigue
authors.forename: Richard E
authors.initials: RE
authors.lastname: Lenski
authors.forename: Dominique
authors.initials: D
authors.lastname: Schneider
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D005075:Biological Evolution; D045647:DNA Glycosylases / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics; D040741:Genetic Load; D016013:Likelihood Functions; D008957:Models, Genetic; D059645:Mutation Rate; D010802:Phylogeny; D011157:Population Dynamics; D011755:Pyrophosphatases / Q000235:genetics
chemical_list: D029968:Escherichia coli Proteins; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; D011755:Pyrophosphatases; C052211:mutT protein, E coli