Genomic buffering mitigates the effects of deleterious mutations in bacteria

Sophie Maisnier-Patin, John R. Roth, Åsa Fredriksson, Thomas Nyström, Otto G. Berg, Dan I. Andersson

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1376-1379
Number of pages4
JournalNature Genetics
Volume37
Issue number12
DOIs
StatePublished - Dec 2005

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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    Maisnier-Patin, S., Roth, J. R., Fredriksson, Å., Nyström, T., Berg, O. G., & Andersson, D. I. (2005). Genomic buffering mitigates the effects of deleterious mutations in bacteria. Nature Genetics, 37(12), 1376-1379. https://doi.org/10.1038/ng1676