Determinants of spontaneous mutation in the bacterium Escherichia coli as revealed by whole-genome sequencing

A complete understanding of evolutionary processes requires that factors determining spontaneous mutation rates and spectra be identified and characterized. Using mutation accumulation followed by whole-genome sequencing, we found that the mutation rates of three widely diverged commensal Escherichi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-11, Vol.112 (44), p.E5990-E5999
Main Authors: Foster, Patricia L, Lee, Heewook, Popodi, Ellen, Townes, Jesse P, Tang, Haixu
Format: Article
Language:English
Subjects:
Alkylation
Bacteria
Biological Sciences
Deoxyribonucleic acid
DNA
DNA damage
DNA Repair
E coli
Escherichia coli
Escherichia coli - genetics
Genes, Bacterial
Genomes
Mutation
PNAS Plus
Polymerase chain reaction
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Summary:A complete understanding of evolutionary processes requires that factors determining spontaneous mutation rates and spectra be identified and characterized. Using mutation accumulation followed by whole-genome sequencing, we found that the mutation rates of three widely diverged commensal Escherichia coli strains differ only by about 50%, suggesting that a rate of 1-2 × 10(-3) mutations per generation per genome is common for this bacterium. Four major forces are postulated to contribute to spontaneous mutations: intrinsic DNA polymerase errors, endogenously induced DNA damage, DNA damage caused by exogenous agents, and the activities of error-prone polymerases. To determine the relative importance of these factors, we studied 11 strains, each defective for a major DNA repair pathway. The striking result was that only loss of the ability to prevent or repair oxidative DNA damage significantly impacted mutation rates or spectra. These results suggest that, with the exception of oxidative damage, endogenously induced DNA damage does not perturb the overall accuracy of DNA replication in normally growing cells and that repair pathways may exist primarily to defend against exogenously induced DNA damage. The thousands of mutations caused by oxidative damage recovered across the entire genome revealed strong local-sequence biases of these mutations. Specifically, we found that the identity of the 3' base can affect the mutability of a purine by oxidative damage by as much as eightfold.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1512136112