ArticleProceedings of the National Academy of Sciences of the United States of America2010
Optimization of DNA polymerase mutation rates during bacterial evolution.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Ineffectual Genomic Error Correction Under Environmental Perturbation Dynamically Regulates Mutational Supply and Robustness.Journal of molecular evolution · 2026Article
- Rapid Evolution of Ionic Silver Resistance inMicroorganisms · 2026Article
- Design and validation of an inducible and curable EvolvR system for directed evolution inFrontiers in bioengineering and biotechnology · 2026Article
- The A, B, C, D's of replicative DNA polymerase fidelity: utilizing high-throughput single-molecule sequencing to understand the molecular basis for DNA polymerase accuracy.Nucleic acids research · 2025Article
- Article
- The fidelity of transcription in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A road map for in vivo evolution experiments with blood-borne parasitic microbes.Molecular ecology resources · 2022Review
- Recent insights into the evolution of mutation rates in yeast.Current opinion in genetics & development · 2022Review
- A CRISPR-guided mutagenic DNA polymerase strategy for the detection of antibiotic-resistant mutations inMolecular therapy. Nucleic acids · 2022Article
- Adaptive antimicrobial resistance, a description of microbial variants, and their relevance to periprosthetic joint infection.The bone & joint journal · 2022Review
- Development of a genome-targeting mutator for the adaptive evolution of microbial cells.Nucleic acids research · 2022Article
- The rate and molecular spectrum of mutation are selectively maintained in yeast.Nature communications · 2021Article
- Coevolutionary and Phylogenetic Analysis of Mimiviral Replication Machinery Suggest the Cellular Origin of Mimiviruses.Molecular biology and evolution · 2021Article
- Adaptive dating and fast proposals: Revisiting the phylogenetic relaxed clock model.PLoS computational biology · 2021Article
- Divergent Evolution of Mutation Rates and Biases in the Long-Term Evolution Experiment with Escherichia coli.Genome biology and evolution · 2020Article
- Somatic maintenance impacts the evolution of mutation rate.BMC evolutionary biology · 2019Article
- Inactivation of a Mismatch-Repair System Diversifies Genotypic Landscape ofFrontiers in microbiology · 2019Article
- Directed evolution of Escherichia coli with lower-than-natural plasmid mutation rates.Nucleic acids research · 2018Article
- CRISPR-guided DNA polymerases enable diversification of all nucleotides in a tunable window.Nature · 2018Article
- High-resolution mapping of DNA polymerase fidelity using nucleotide imbalances and next-generation sequencing.Nucleic acids research · 2018Article
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Authors and funding
3 authors.
Funding
Abstract
Mutation rate is an important determinant of evolvability. The optimal mutation rate for different organisms during evolution has been modeled in silico and tested in vivo, predominantly through pairwise comparisons. To characterize the fitness landscape across a broad range of mutation rates, we generated a panel of 66 DNA polymerase I mutants in Escherichia coli with comparable growth properties, yet with differing DNA replication fidelities, spanning 10(3)-fold higher and lower than that of wild type. These strains were competed for 350 generations in six replicate cultures in two different environments. A narrow range of mutation rates, 10- to 47-fold greater than that of wild type, predominated after serial passage. Mutants exhibiting higher mutation rates were not detected, nor were wild-type or antimutator strains. Winning clones exhibited shorter doubling times, greater maximum culture densities, and a growth advantages in pairwise competition relative to their precompetition ancestors, indicating the acquisition of adaptive phenotypes. To investigate the basis for mutator selection, we undertook a large series of pairwise competitions between mutator and wild-type strains under conditions where, in most cases, one strain completely overtook the culture within 18 days. Mutators were the most frequent winners but wild-type strains were also observed winning, suggesting that the competitive advantage of mutators is due to a greater probability of developing selectably advantageous mutations rather than from an initial growth advantage conferred by the polymerase variant itself. Our results indicate that under conditions where organism fitness is not yet maximized for a particular environment, competitive adaptation may be facilitated by enhanced mutagenesis.
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