Evolution of mutation rates in hypermutable populations of<i>Escherichia coli</i>propagated at very small effective population size

Singh, Tanya; Meredith, Hyun; Sniegowski, Paul D.

doi:10.1098/rsbl.2016.0849

Cited by 12 publications

(9 citation statements)

References 19 publications

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“…While we cannot predict whether our hypermutable populations would eventually go extinct, the observation that their mutation rate can decrease adaptively makes this less likely. Indeed, recent mutation accumulation experiments with small bacterial populations suggested that populations with higher mutation rates tend to go extinct more often and have reduced fitness than populations with lower mutation rates [ 47 ]. Of the several "mutation rate genome" genes mutated in MR XL strains, only rpoS was found in all eight evolved MR XL replicate populations.…”

Section: Discussionmentioning

confidence: 99%

High mutation rates limit evolutionary adaptation in Escherichia coli

et al. 2018

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Mutation is fundamental to evolution, because it generates the genetic variation on which selection can act. In nature, genetic changes often increase the mutation rate in systems that range from viruses and bacteria to human tumors. Such an increase promotes the accumulation of frequent deleterious or neutral alleles, but it can also increase the chances that a population acquires rare beneficial alleles. Here, we study how up to 100-fold increases in Escherichia coli’s genomic mutation rate affect adaptive evolution. To do so, we evolved multiple replicate populations of asexual E. coli strains engineered to have four different mutation rates for 3000 generations in the laboratory. We measured the ability of evolved populations to grow in their original environment and in more than 90 novel chemical environments. In addition, we subjected the populations to whole genome population sequencing. Although populations with higher mutation rates accumulated greater genetic diversity, this diversity conveyed benefits only for modestly increased mutation rates, where populations adapted faster and also thrived better than their ancestors in some novel environments. In contrast, some populations at the highest mutation rates showed reduced adaptation during evolution, and failed to thrive in all of the 90 alternative environments. In addition, they experienced a dramatic decrease in mutation rate. Our work demonstrates that the mutation rate changes the global balance between deleterious and beneficial mutational effects on fitness. In contrast to most theoretical models, our experiments suggest that this tipping point already occurs at the modest mutation rates that are found in the wild.

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Section: Discussionmentioning

confidence: 99%

High mutation rates limit evolutionary adaptation in Escherichia coli

et al. 2018

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“…But when the rate of fitness increase slowed down considerably, one of the mutator lines experienced a decrease in its mutation rate [46]. Several other experiments have also provided evidence for the rise in frequency of nonmutator allele in an adapted population [45,30,29,37].…”

Section: Introductionmentioning

confidence: 99%

Fixation probability of a nonmutator in a large population of asexual mutators

Jain

James

2017

Journal of Theoretical Biology

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In an adapted population of mutators in which most mutations are deleterious, a nonmutator that lowers the mutation rate is under indirect selection and can sweep to fixation. Using a multitype branching process, we calculate the fixation probability of a rare nonmutator in a large population of asexual mutators. We show that when beneficial mutations are absent, the fixation probability is a nonmonotonic function of the mutation rate of the mutator: it first increases sublinearly and then decreases exponentially. We also find that beneficial mutations can enhance the fixation probability of a nonmutator. Our analysis is relevant to an understanding of recent experiments in which a reduction in the mutation rates has been observed.

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“…High genome-wide mutation rates increase the occurrence of both beneficial and deleterious mutations. An excess of deleterious mutations slows adaptation and potentially causes extinction [2,3]. The effects of most mutations range from selectively neutral to deleterious [4], but even modest numbers of deleterious mutations can reduce individual viability [5] and increase the mutation load [6,7].…”

Section: Introductionmentioning

confidence: 99%

Evolutionary innovation using EDGE, a system for localized elevated mutagenesis

2020

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Mutations arising across the whole genome can hinder the emergence of evolutionary innovation required for adaptation because many mutations are deleterious. This trade-off is overcome by elevated mutagenesis to localized loci. Examples include phase variation and diversity-generating retroelements. However, these mechanisms are rare in nature; and all have narrow mutational spectra limiting evolutionary innovation. Here, we engineer a platform of Experimental Designed Genic Evolution (EDGE) to study the potential for evolutionary novelty at a single locus. Experimental evolution with EDGE shows that bacterial resistance to a novel antibiotic readily evolves, provided that elevated mutagenesis is focused on a relevant gene. A model is proposed to account for the cost and benefit of such single loci to adaptation in a changing environment and explains their high mutation rates, limited innovation, and the rarity of localized mutagenesis in nature. Overall, our results suggest that localized mutation systems can facilitate continuing adaptive evolution without necessarily restricting the spectrum of mutations. EDGE has utility in dissecting the complex process of adaptation with its localized, efficient evolution.

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Evolution of mutation rates in hypermutable populations ofEscherichia colipropagated at very small effective population size

Cited by 12 publications

References 19 publications

High mutation rates limit evolutionary adaptation in Escherichia coli

High mutation rates limit evolutionary adaptation in Escherichia coli

Fixation probability of a nonmutator in a large population of asexual mutators

Evolutionary innovation using EDGE, a system for localized elevated mutagenesis

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