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Cited by 681Evolution and Genetic DynamicsDNA Repair MechanismsBacterial Genetics and Biotechnology

Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia coli as determined by whole-genome sequencing

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Lee, Heewook, Popodi, Ellen, Tang, Haixu, Foster, Patricia L.·2012·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1210309109PMC PMC3478608
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Abstract

Knowledge of the rate and nature of spontaneous mutation is fundamental to understanding evolutionary and molecular processes. In this report, we analyze spontaneous mutations accumulated over thousands of generations by wild-type Escherichia coli and a derivative defective in mismatch repair (MMR), the primary pathway for correcting replication errors. The major conclusions are (i) the mutation rate of a wild-type E. coli strain is ~1 × 10(-3) per genome per generation; (ii) mutations in the wild-type strain have the expected mutational bias for G:C > A:T mutations, but the bias changes to A:T > G:C mutations in the absence of MMR; (iii) during replication, A:T > G:C transitions preferentially occur with A templating the lagging strand and T templating the leading strand, whereas G:C > A:T transitions preferentially occur with C templating the lagging strand and G templating the leading strand; (iv) there is a strong bias for transition mutations to occur at 5'ApC3'/3'TpG5' sites (where bases 5'A and 3'T are mutated) and, to a lesser extent, at 5'GpC3'/3'CpG5' sites (where bases 5'G and 3'C are mutated); (v) although the rate of small (≤4 nt) insertions and deletions is high at repeat sequences, these events occur at only 1/10th the genomic rate of base-pair substitutions. MMR activity is genetically regulated, and bacteria isolated from nature often lack MMR capacity, suggesting that modulation of MMR can be adaptive. Thus, comparing results from the wild-type and MMR-defective strains may lead to a deeper understanding of factors that determine mutation rates and spectra, how these factors may differ among organisms, and how they may be shaped by environmental conditions.

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  • During bacterial replication, the spontaneous mutation rate is 2.2 × 10−10 mutations per nucleotide per generation, or 1.0 × 10−3 mutations per genome per generation.

    “However, during bacterial replication, the spontaneous mutation rate is 2.2 × 10−10 mutations per nucleotide per generation, or 1.0 × 10−3 mutations per genome per generation [68].”

    From DNA Data Storage. (2023) · cites this paper as [68]

    The section “Spontaneous Mutation Rate of Wild-Type E. coli Is Lower than Expected” gives both quoted rates. The Discussion specifies that the estimate is for a wild-type E. coli strain growing on rich medium; the citing sentence presents it as a rate for bacterial replication generally. (LLM, conf=0.86)

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Authors
Lee, H., Popodi, E., Tang, H., & Foster, P. L.
Affiliations
  • School of Informatics and Computing and
  • Indiana University Bloomington (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2012-09-18
Volume
109
Issue
41
Pages
E2774-83
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1210309109
PMC
PMC3478608
OpenAlex
W2019385975
Cited by
681
References
86
Citations by year
2026: 28 · 2025: 44 · 2024: 59 · 2023: 49 · 2022: 52 · 2021: 82 · 2020: 51 · 2019: 49 · 2018: 49 · 2017: 57 · 2016: 62 · 2015: 48 · 2014: 28 · 2013: 21 · 2012: 2
FWCI
19.02
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Multidisciplinary University Research Initiative (W911NF-09-1-0444)
  • Army Research Office (W911NF-09-1-0444, W911NF)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
spontaneous mutation, mutation rate, mutation spectrum, Escherichia coli, DNA mismatch repair, mutational bias, transition mutations, CpG sites, insertion-deletion mutations, repetitive DNA, replication errors, bacterial evolution
MeSH terms
MutL Proteins, Adenosine Triphosphatases, Base Sequence, Binding Sites, DNA Replication, DNA, Bacterial, Escherichia coli, Genes, Bacterial, Monte Carlo Method, Mutation, Selection, Genetic, Genome, Bacterial, Point Mutation, Sequence Analysis, DNA, DNA Methylation, Polymorphism, Single Nucleotide, Escherichia coli Proteins, DNA Mismatch Repair, INDEL Mutation, Mutation Rate

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