Genomic buffering mitigates the effects of deleterious mutations in bacteria

Nat Genet. 2005 Dec;37(12):1376-9. doi: 10.1038/ng1676. Epub 2005 Nov 6.


The relationship between the number of randomly accumulated mutations in a genome and fitness is a key parameter in evolutionary biology. Mutations may interact such that their combined effect on fitness is additive (no epistasis), reinforced (synergistic epistasis) or mitigated (antagonistic epistasis). We measured the decrease in fitness caused by increasing mutation number in the bacterium Salmonella typhimurium using a regulated, error-prone DNA polymerase (polymerase IV, DinB). As mutations accumulated, fitness costs increased at a diminishing rate. This suggests that random mutations interact such that their combined effect on fitness is mitigated and that the genome is buffered against the fitness reduction caused by accumulated mutations. Levels of the heat shock chaperones DnaK and GroEL increased in lineages that had accumulated many mutations, and experimental overproduction of GroEL further increased the fitness of lineages containing deleterious mutations. These findings suggest that overexpression of chaperones contributes to antagonistic epistasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics*
  • Chaperonin 60 / metabolism
  • DNA Polymerase beta / metabolism
  • Epistasis, Genetic*
  • Genome, Bacterial*
  • HSP70 Heat-Shock Proteins / metabolism
  • Molecular Chaperones / metabolism
  • Mutagenesis
  • Mutation*
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / physiology


  • Chaperonin 60
  • HSP70 Heat-Shock Proteins
  • Molecular Chaperones
  • DNA Polymerase beta