The Fixation Probability of Rare Mutators in Finite Asexual Populations

Wylie, C. Scott; Ghim, Cheol-Min; Kessler, David A.; Levine, Herbert

doi:10.1534/genetics.108.094532

Cited by 38 publications

(58 citation statements)

References 57 publications

(116 reference statements)

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“…Instead, we consider the simplest possible situation and use this to highlight some of the important factors involved in mutator dynamics in the presence of beneficial mutations. Our analysis is much less detailed than recent work by Tanaka et al (2003) and Wylie et al (2009). However, while these studies provide a more complete theoretical description of mutator dynamics in the presence of beneficial mutations, they are valid only when deleterious mutations have very strong effects and can be treated as effectively lethal.…”

Section: Beneficial Mutationsmentioning

confidence: 90%

The Balance Between Mutators and Nonmutators in Asexual Populations

Desai

Fisher

2011

Genetics

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Mutator alleles, which elevate an individual's mutation rate from 10 to 10,000-fold, have been found at high frequencies in many natural and experimental populations. Mutators are continually produced from nonmutators, often due to mutations in mismatch-repair genes. These mutators gradually accumulate deleterious mutations, limiting their spread. However, they can occasionally hitchhike to high frequencies with beneficial mutations. We study the interplay between these effects. We first analyze the dynamics of the balance between the production of mutator alleles and their elimination due to deleterious mutations. We find that when deleterious mutation rates are high in mutators, there will often be many "young," recently produced mutators in the population, and the fact that deleterious mutations only gradually eliminate individuals from a population is important. We then consider how this mutator-nonmutator balance can be disrupted by beneficial mutations and analyze the circumstances in which fixation of mutator alleles is likely. We find that dynamics is crucial: even in situations where selection on average acts against mutators, so they cannot stably invade, the mutators can still occasionally generate beneficial mutations and hence be important to the evolution of the population.

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Section: Beneficial Mutationsmentioning

confidence: 90%

The Balance Between Mutators and Nonmutators in Asexual Populations

Desai

Fisher

2011

Genetics

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“…1997; Andre and Godelle 2006; Wylie et al. 2009; Desai and Fisher 2011) and our study is that here the mutator population is assumed to be at mutation‐selection equilibrium and is therefore not under positive selection. However, compensatory mutations that alleviate the effect of deleterious mutations are included in our model.…”

Section: Introductionmentioning

confidence: 99%

Fixation probability of rare nonmutator and evolution of mutation rates

James

Jain

2016

Ecology and Evolution

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Although mutations drive the evolutionary process, the rates at which the mutations occur are themselves subject to evolutionary forces. Our purpose here is to understand the role of selection and random genetic drift in the evolution of mutation rates, and we address this question in asexual populations at mutation‐selection equilibrium neglecting selective sweeps. Using a multitype branching process, we calculate the fixation probability of a rare nonmutator in a large asexual population of mutators and find that a nonmutator is more likely to fix when the deleterious mutation rate of the mutator population is high. Compensatory mutations in the mutator population are found to decrease the fixation probability of a nonmutator when the selection coefficient is large. But, surprisingly, the fixation probability changes nonmonotonically with increasing compensatory mutation rate when the selection is mild. Using these results for the fixation probability and a drift‐barrier argument, we find a novel relationship between the mutation rates and the population size. We also discuss the time to fix the nonmutator in an adapted population of asexual mutators, and compare our results with experiments.

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“…Theoretical studies began exploring the population genetics of mutation rate modifier alleles in the 1960s, and significant theory papers on mutation rate evolution have appeared in every decade since (Kimura, 1967;Leigh, 1970Leigh, , 1973Ishii et al, 1989;Taddei et al, 1997;Johnson, 1999;Andre and Godelle, 2006;Gerrish et al, 2007;Lynch, 2008;Wylie et al, 2009;Desai and Fisher, 2011). Direct experimental work on the population genetics of mutation rate modifiers began in the 1970s (Gibson et al, 1970;Cox and Gibson, 1974) and has grown rapidly in recent years (Giraud et al, 2001;Notley-McRobb et al, 2002b;Thompson et al, 2006;Pal et al, 2007;Gentile et al, 2011;Raynes et al, 2011Raynes et al, , 2012Raynes et al, , 2014McDonald et al, 2012;Maharjan et al, 2013;Wielgoss et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Experimental evolution and the dynamics of genomic mutation rate modifiers

Raynes

Sniegowski

2014

Heredity

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Because genes that affect mutation rates are themselves subject to mutation, mutation rates can be influenced by natural selection and other evolutionary forces. The population genetics of mutation rate modifier alleles has been a subject of theoretical interest for many decades. Here, we review experimental contributions to our understanding of mutation rate modifier dynamics. Numerous evolution experiments have shown that mutator alleles (modifiers that elevate the genomic mutation rate) can readily rise to high frequencies via genetic hitchhiking in non-recombining microbial populations. Whereas these results certainly provide an explanatory framework for observations of sporadically high mutation rates in pathogenic microbes and in cancer lineages, it is nonetheless true that most natural populations have very low mutation rates. This raises the interesting question of how mutator hitchhiking is suppressed or its phenotypic effect reversed in natural populations. Very little experimental work has addressed this question; with this in mind, we identify some promising areas for future experimental investigation.

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The Fixation Probability of Rare Mutators in Finite Asexual Populations

Cited by 38 publications

References 57 publications

The Balance Between Mutators and Nonmutators in Asexual Populations

The Balance Between Mutators and Nonmutators in Asexual Populations

Fixation probability of rare nonmutator and evolution of mutation rates

Experimental evolution and the dynamics of genomic mutation rate modifiers

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