Mutator dynamics in fluctuating environments

Travis, Justin M. J.; Travis, Emma R.

doi:10.1098/rspb.2001.1902

Cited by 75 publications

(77 citation statements)

References 34 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The cycle repeats itself many times, and Leigh (1970) finds that the long-term ESS mutation rate is equal to the rate of environmental change. Over the years, this basic model was improved by incorporating the effects of timing of environmental changes, varying selective coefficients (Ishii et al 1989), intermediate genotypes (Travis and Travis 2002), and multiple mutable sites (Palmer and Lipsitch 2006).…”

Section: Discussionmentioning

confidence: 99%

The Fixation Probability of Rare Mutators in Finite Asexual Populations

et al. 2009

View full text Add to dashboard Cite

A mutator is an allele that increases the mutation rate throughout the genome by disrupting some aspect of DNA replication or repair. Mutators that increase the mutation rate by the order of 100-fold have been observed to spontaneously emerge and achieve high frequencies in natural populations and in longterm laboratory evolution experiments with Escherichia coli. In principle, the fixation of mutator alleles is limited by (i) competition with mutations in wild-type backgrounds, (ii) additional deleterious mutational load, and (iii) random genetic drift. Using a multiple-locus model and employing both simulation and analytic methods, we investigate the effects of these three factors on the fixation probability P fix of an initially rare mutator as a function of population size N, beneficial and deleterious mutation rates, and the strength of mutations s. Our diffusion-based approximation for P fix successfully captures effects ii and iii when selection is fast compared to mutation (m=s > 1). This enables us to predict the conditions under which mutators will be evolutionarily favored. Surprisingly, our simulations show that effect i is typically small for strong-effect mutators. Our results agree semiquantitatively with existing laboratory evolution experiments and suggest future experimental directions.

show abstract

Section: Discussionmentioning

confidence: 99%

The Fixation Probability of Rare Mutators in Finite Asexual Populations

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The equilibrium frequency of micro-organisms with high mutation rate (mutators) and their dynamics, particularly in fluctuating environments Travis & Travis 2002), depend strongly on the values of U d and s d . Mutators are expected to be maintained in natural populations at a low frequency because they generate more deleterious mutations and therefore suffer from a bigger mutational load.…”

Section: Introductionmentioning

confidence: 99%

Rate and effects of spontaneous mutations that affect fitness in mutatorEscherichia coli

Trindade

Perfeito

Gordo

2010

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

Knowledge of the mutational parameters that affect the evolution of organisms is of key importance in understanding the evolution of several characteristics of many natural populations, including recombination and mutation rates. In this study, we estimated the rate and mean effect of spontaneous mutations that affect fitness in a mutator strain of Escherichia coli and review some of the estimation methods associated with mutation accumulation (MA) experiments. We performed an MA experiment where we followed the evolution of 50 independent mutator lines that were subjected to repeated bottlenecks of a single individual for approximately 1150 generations. From the decline in mean fitness and the increase in variance between lines, we estimated a minimum mutation rate to deleterious mutations of 0.005 (+0.001 with 95% confidence) and a maximum mean fitness effect per deleterious mutation of 0.03 (+0.01 with 95% confidence). We also show that any beneficial mutations that occur during the MA experiment have a small effect on the estimate of the rate and effect of deleterious mutations, unless their rate is extremely large. Extrapolating our results to the wild-type mutation rate, we find that our estimate of the mutational effects is slightly larger and the inferred deleterious mutation rate slightly lower than previous estimates obtained for non-mutator E. coli.

show abstract

“…Hypermutable mutants can become established in asexual populations while they adapt to changed environments owing to their higher per capita probability of discovering rare beneficial mutations compared with nonmutators (14)(15)(16)(17)(18). Although hypermutable genotypes should produce beneficial mutations at a higher rate than their less mutable counterparts, they do not necessarily increase the rate of adaptation to a corresponding, or even measurable, degree.…”

mentioning

confidence: 99%

Mutation rate dynamics in a bacterial population reflect tension between adaptation and genetic load

Wielgoss

Barrick

Tenaillon

et al. 2012

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

253

302

View full text Add to dashboard Cite

Mutations are the ultimate source of heritable variation for evolution. Understanding how mutation rates themselves evolve is thus essential for quantitatively understanding many evolutionary processes. According to theory, mutation rates should be minimized for well-adapted populations living in stable environments, whereas hypermutators may evolve if conditions change. However, the long-term fate of hypermutators is unknown. Using a phylogenomic approach, we found that an adapting Escherichia coli population that first evolved a mutT hypermutator phenotype was later invaded by two independent lineages with mutY mutations that reduced genome-wide mutation rates. Applying neutral theory to synonymous substitutions, we dated the emergence of these mutations and inferred that the mutT mutation increased the point-mutation rate by ∼150-fold, whereas the mutY mutations reduced the rate by ∼40-60%, with a corresponding decrease in the genetic load. Thus, the long-term fate of the hypermutators was governed by the selective advantage arising from a reduced mutation rate as the potential for further adaptation declined. experimental evolution | genomics | mutators | phylogenomics M utations are the ultimate source of heritable variation for evolution. Therefore, understanding how selection can change mutation rates is crucial for quantitatively describing evolutionary processes (1). More mutations are deleterious than beneficial (2), and organisms from bacteria to eukaryotes encode proofreading and repair enzymes that reduce mutation rates (3). If selection for beneficial mutations is weak relative to selection against deleterious mutations, then the rate of adaptation in asexual populations is maximized at some intermediate mutation rate (4). However, when populations encounter new environments, selection for beneficial mutations can be strong (5), and much higher mutation rates may evolve. Indeed, surveys of laboratory populations of microbes (6-10), clinical isolates of bacterial pathogens (11,12), and some types of eukaryotic tumors (13) have revealed a surprisingly high proportion of lineages that have evolved genetic defects in repair pathways. These hypermutators often have 10-to 100-fold increased mutation rates, and such elevated mutation rates can accelerate the progression of chronic diseases and the evolution of resistance to therapeutic agents.Hypermutable mutants can become established in asexual populations while they adapt to changed environments owing to their higher per capita probability of discovering rare beneficial mutations compared with nonmutators (14-18). Although hypermutable genotypes should produce beneficial mutations at a higher rate than their less mutable counterparts, they do not necessarily increase the rate of adaptation to a corresponding, or even measurable, degree. In large asexual populations, the waiting time for new beneficial mutations to occur may be short relative to the time required for a mutant to increase from one individual to fixation in the population, assuming the be...

show abstract

Mutator dynamics in fluctuating environments

Cited by 75 publications

References 34 publications

The Fixation Probability of Rare Mutators in Finite Asexual Populations

The Fixation Probability of Rare Mutators in Finite Asexual Populations

Rate and effects of spontaneous mutations that affect fitness in mutatorEscherichia coli

Mutation rate dynamics in a bacterial population reflect tension between adaptation and genetic load

Contact Info

Product

Resources

About