Estimate of the genomic mutation rate deleterious to overall fitness in E. coli

Kibota, Travis T.

doi:10.1016/0168-9525(96)81473-9

Cited by 80 publications

(123 citation statements)

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“…Of the 1.2 × 10 7 possible codon-changing BPSs in the E. coli ge- (7,27), which is, at most, only a fourth of the total mutation rate observed here. The rate of beneficial mutations is even lower, and, in addition, most beneficial and deleterious mutations have only small (<3%) effects on fitness (7,27). Taken together, our results with the wild-type strain are consistent with these findings and support the basic premise that the MA protocol minimizes selection and allows mutations to accumulate in a nearly neutral fashion.…”

Section: Resultsmentioning

confidence: 99%

“…Selection within a colony is minimal because most new mutations arise during the last few generations of growth when the population is large. Furthermore, the great majority of mutations have no fitness effects, and of those that do, the effects are small (6)(7)(8)(9). The application of whole-genome sequencing to MA lines has made this protocol an extremely valuable way to determine a complete and nearly unbiased picture of mutation profiles.…”

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confidence: 99%

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Rate and molecular spectrum of spontaneous mutations in the bacteriumEscherichia colias determined by whole-genome sequencing

Lee¹,

Popodi

Tang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

648

131

859

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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. evolution | mutation accumulation | neutral mutation | mutational hotspots | indels M utations are the source of variation upon which natural selection acts; thus, a complete understanding of evolutionary processes must include an accurate assessment of mutation rates and of the molecular spectrum of mutational events. In addition, we need to know whether, and how, intrinsic and extrinsic factors influence mutational processes. This understanding must be founded on baseline parameters established by analyzing mutations that accumulate in a neutral fashion, unbiased by selective pressures. Much of our knowledge of spontaneous mutation is based on mutations that occur in nonessential reporter genes during short-term laboratory culture of microorganisms (1). An alternative approach is to compare presumably neutral mutations that have accumulated over evolutionary time periods in diverged species (2). Both methods have substantial uncertainties. The experimental approach may use reporter loci that are not representative of the whole genome and necessarily incorporates assumptions about the expression and neutrality of the mutant phenotypes. The historical approach relies on estimated divergence times and the absence of selective pressure on synonymous sequence changes. High-throughput whole-genome sequencing allows some of these limitations to be...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Rate and molecular spectrum of spontaneous mutations in the bacteriumEscherichia colias determined by whole-genome sequencing

Lee¹,

Popodi

Tang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

648

131

859

View full text Add to dashboard Cite

show abstract

“…Genetic drift in single-cell bottlenecked lines of E. coli is strong enough to prevent the operation of selection on all but mutations with very large effects (31), and numerous prior studies of this sort have validated the effectively nonselective nature of MA experiments (27,28,33,38,39). However, to directly test whether selection might have biased the mutation rate/spectrum (e.g., by enriching for mutations conferring norfloxacin resistance), we examined the synonymous and nonsynonymous status of each coding-region BPS (Dataset S1, Table S2).…”

Section: Resultsmentioning

confidence: 99%

“…MA experiments using bacteria are performed by repeatedly passing large numbers of initially identical lines through single-cell bottlenecks, a procedure that prevents natural selection from promoting or eradicating nearly all mutations, except the small subset with extremely large effects (31). This MA/WGS procedure provides an essentially unbiased, genomewide view of the rate and full molecular spectrum of mutations, and has yielded accurate estimates of these features in a wide variety of prokaryotic and eukaryotic microbes (27,28,(32)(33)(34).…”

Section: Significancementioning

confidence: 99%

Antibiotic treatment enhances the genome-wide mutation rate of target cells

Long

Miller

Strauss

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

184

143

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Although it is well known that microbial populations can respond adaptively to challenges from antibiotics, empirical difficulties in distinguishing the roles of de novo mutation and natural selection have left several issues unresolved. Here, we explore the mutational properties of Escherichia coli exposed to long-term sublethal levels of the antibiotic norfloxacin, using a mutation accumulation design combined with whole-genome sequencing of replicate lines. The genome-wide mutation rate significantly increases with norfloxacin concentration. This response is associated with enhanced expression of error-prone DNA polymerases and may also involve indirect effects of norfloxacin on DNA mismatch and oxidative-damage repair. Moreover, we find that acquisition of antibiotic resistance can be enhanced solely by accelerated mutagenesis, i.e., without direct involvement of selection. Our results suggest that antibiotics may generally enhance the mutation rates of target cells, thereby accelerating the rate of adaptation not only to the antibiotic itself but to additional challenges faced by invasive pathogens.antibiotic resistance | mutation rate | resistance evolution | DNA repair | low-fidelity polymerases

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“…Eventually a threshold is crossed, and the population spirals into extinction via a ''mutational meltdown,'' as can be seen in ciliated protozoans and fibroblast cultures, for example (Smith and Pereira-Smith 1977;Tagaki and Yoshida 1980). Mutation-accumulation (MA) experiments have been used effectively for .40 years to address questions related to the buildup of deleterious mutations in populations such as those of Arabidopsis, Caenorhabditis elegans, Daphnia, Drosophila, Escherichia coli, Saccharomyces cerevisiae, and others (reviewed in Mukai 1964;Kibota and Lynch 1996;Lynch and Walsh 1998;Schultz et al 1999;Pfrender and Lynch 2000;Zeyl et al 2001;Estes et al 2004). A species lineage is propagated in a very controlled environment over a large number of generations and is typically forced through a bottleneck in size each generation to exacerbate the effects of random genetic drift.…”

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confidence: 99%

Accumulation of Deleterious Mutations in Small Abiotic Populations of RNA

Soll¹,

Arenas

Lehman

2007

Genetics

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The accumulation of slightly deleterious mutations in populations leads to the buildup of a genetic load and can cause the extinction of populations of small size. Mutation-accumulation experiments have been used to study this process in a wide variety of organisms, yet the exact mutational underpinnings of genetic loads and their fitness consequences remain poorly characterized. Here, we use an abiotic system of RNA populations evolving continuously in vitro to examine the molecular events that can instigate a genetic load. By tracking the fitness decline of ligase ribozyme populations with bottleneck sizes between 100 and 3000 molecules, we detected the appearance and subsequent fixation of both slightly deleterious mutations and advantageous mutations. Smaller populations went extinct in significantly fewer generations than did larger ones, supporting the notion of a mutational meltdown. These data suggest that mutation accumulation was an important evolutionary force in the prebiotic RNA world and that mechanisms such as recombination to ameliorate genetic loads may have been in place early in the history of life.

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Estimate of the genomic mutation rate deleterious to overall fitness in E. coli

Cited by 80 publications

References 0 publications

Rate and molecular spectrum of spontaneous mutations in the bacteriumEscherichia colias determined by whole-genome sequencing

Rate and molecular spectrum of spontaneous mutations in the bacteriumEscherichia colias determined by whole-genome sequencing

Antibiotic treatment enhances the genome-wide mutation rate of target cells

Accumulation of Deleterious Mutations in Small Abiotic Populations of RNA

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