Mutation rate dynamics in a bacterial population reflect tension between adaptation and genetic load

Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):222-7. doi: 10.1073/pnas.1219574110. Epub 2012 Dec 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Biological / genetics*
  • Biological Evolution*
  • DNA Glycosylases / genetics
  • Escherichia coli / genetics*
  • Escherichia coli Proteins / genetics
  • Genetic Load*
  • Likelihood Functions
  • Models, Genetic
  • Mutation Rate*
  • Phylogeny
  • Population Dynamics
  • Pyrophosphatases / genetics


  • Escherichia coli Proteins
  • DNA Glycosylases
  • mutY adenine glycosylase
  • Pyrophosphatases
  • mutT protein, E coli