scholarly journals Evolution of mutation rates in rapidly adapting asexual populations

2016 ◽  
Author(s):  
Benjamin H. Good ◽  
Michael M. Desai
Keyword(s):  
Mutation Rate ◽  
Evolutionary Dynamics ◽  
Empirical Work ◽  
Indirect Selection ◽  
Microbial Evolution ◽  
Mutation Rates ◽  
Fixation Probability ◽  
Deleterious Mutations ◽  
Clonal Interference ◽  
Asexual Population

Mutator and antimutator alleles often arise and spread in both natural microbial populations and laboratory evolution experiments. The evolutionary dynamics of these mutation rate modifiers are determined by indirect selection on linked beneficial and deleterious mutations. These indirect selection pressures have been the focus of much earlier theoretical and empirical work, but we still have a limited analytical understanding of how the interplay between hitchhiking and deleterious load influences the fates of modifier alleles. Our understanding is particularly limited when clonal interference is common, which is the regime of primary interest in laboratory microbial evolution experiments. Here, we calculate the fixation probability of a mutator or antimutator allele in a rapidly adapting asexual population, and we show how this quantity depends on the population size, the beneficial and deleterious mutation rates, and the strength of a typical driver mutation. In the absence of deleterious mutations, we find that clonal interference enhances the fixation probability of mutators, even as they provide a diminishing benefit to the overall rate of adaptation. When deleterious mutations are included, natural selection pushes the population towards a stable mutation rate that can be suboptimal for the adaptation of the population as a whole. The approach to this stable mutation rate is not necessarily monotonic, and selection can favor mutator and antimutator alleles that overshoot the stable mutation rate by substantial amounts.

scholarly journals Beneficial Mutations, Hitchhiking and the Evolution of Mutation Rates in Sexual Populations

Genetics ◽  
1999 ◽  
Vol 151 (4) ◽  
pp. 1621-1631 ◽  
Author(s):  
Toby Johnson
Keyword(s):  
Mutation Rate ◽  
Indirect Selection ◽  
Mutation Rates ◽  
Deleterious Mutations ◽  
Heritable Variation ◽  
Asexual Population ◽  
Beneficial Mutations ◽  
Long Term Effect ◽  
The Cost ◽  
Substantial Change

Abstract Natural selection acts in three ways on heritable variation for mutation rates. A modifier allele that increases the mutation rate is (i) disfavored due to association with deleterious mutations, but is also favored due to (ii) association with beneficial mutations and (iii) the reduced costs of lower fidelity replication. When a unique beneficial mutation arises and sweeps to fixation, genetic hitchhiking may cause a substantial change in the frequency of a modifier of mutation rate. In previous studies of the evolution of mutation rates in sexual populations, this effect has been underestimated. This article models the long-term effect of a series of such hitchhiking events and determines the resulting strength of indirect selection on the modifier. This is compared to the indirect selection due to deleterious mutations, when both types of mutations are randomly scattered over a given genetic map. Relative to an asexual population, increased levels of recombination reduce the effects of beneficial mutations more rapidly than those of deleterious mutations. However, the role of beneficial mutations in determining the evolutionarily stable mutation rate may still be significant if the function describing the cost of high-fidelity replication has a shallow gradient.

scholarly journals Epigenetically Inherited Mutation Rates Predicted to Maximize Adaptation Rates

2021 ◽  
Author(s):  
Yoav Ram ◽  
Yitzhak Tzachi Pilpel ◽  
Gabriela Aleksandra Lobinska
Keyword(s):  
Mutation Rate ◽  
Adaptive Evolution ◽  
Evolutionary Dynamics ◽  
Epigenetic Inheritance ◽  
Fitness Landscapes ◽  
Mutation Rates ◽  
Switching Rate ◽  
Asexual Population ◽  
Parental Phenotype ◽  
Rugged Fitness Landscapes

The mutation rate is an important determinant of evolutionary dynamics. Because the mutation rate determines the rate of appearance of beneficial and deleterious mutations, it is subject to second-order selection. The mutation rate varies between and within species and populations, increases under stress, and is genetically controlled by mutator alleles. The mutation rate may also vary among genetically identical individuals: empirical evidence from bacteria suggests that the mutation rate may be affected by translation errors and expression noise in various proteins (1). Importantly, this non-genetic variation may be heritable via transgenerational epigenetic inheritance. Here we investigate how the inheritance mode of the mutation rate affects the rate of adaptive evolution on rugged fitness landscapes. We model an asexual population with two mutation rate phenotypes, non-mutator and mutator. An offspring may switch from its parental phenotype to the other phenotype. The rate of switching between the mutation rate phenotypes is allowed to span a range of values. Thus, the mutation rate can be interpreted as a genetically inherited trait when the switching rate is low, as an epigenetically inherited trait when the switching rate is intermediate, or as a randomly determined trait when the switching rate is high. We find that epigenetically inherited mutation rates result in the highest rates of adaptation on rugged fitness landscapes for most realistic parameter sets. This is because an intermediate switching rate can maintain the association between a mutator phenotype and pre-existing mutations, which facilitates the crossing of fitness valleys. Our results provide a rationale for the evolution of epigenetic inheritance of the mutation rate, suggesting that it could have been selected because it facilitates adaptive evolution.

scholarly journals Sign of selection on mutation rate modifiers depends on population size

2018 ◽  
Vol 115 (13) ◽  
pp. 3422-3427 ◽  
Author(s):  
Yevgeniy Raynes ◽  
C. Scott Wylie ◽  
Paul D. Sniegowski ◽  
Daniel M. Weinreich
Keyword(s):  
Population Size ◽  
Mutation Rate ◽  
Genetic System ◽  
Indirect Selection ◽  
Mutation Rates ◽  
Deleterious Mutations ◽  
Fitness Effects ◽  
Sign Inversion ◽  
Large Populations ◽  
The Cost

The influence of population size (N) on natural selection acting on alleles that affect fitness has been understood for almost a century. AsNdeclines, genetic drift overwhelms selection and alleles with direct fitness effects are rendered neutral. Often, however, alleles experience so-called indirect selection, meaning they affect not the fitness of an individual but the fitness distribution of its offspring. Some of the best-studied examples of indirect selection include alleles that modify aspects of the genetic system such as recombination and mutation rates. Here, we use analytics, simulations, and experimental populations ofSaccharomyces cerevisiaeto examine the influence ofNon indirect selection acting on alleles that increase the genomic mutation rate (mutators). Mutators experience indirect selection via genomic associations with beneficial and deleterious mutations they generate. We show that, asNdeclines, indirect selection driven by linked beneficial mutations is overpowered by drift before drift can neutralize the cost of the deleterious load. As a result, mutators transition from being favored by indirect selection in large populations to being disfavored asNdeclines. This surprising phenomenon of sign inversion in selective effect demonstrates that indirect selection on mutators exhibits a profound and qualitatively distinct dependence onN.

scholarly journals Mutation rate dynamics reflect ecological change in an emerging zoonotic pathogen

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009864
Author(s):  
Gemma G. R. Murray ◽  
Andrew J. Balmer ◽  
Josephine Herbert ◽  
Nazreen F. Hadijirin ◽  
Caroline L. Kemp ◽  
...  
Keyword(s):  
Genome Size ◽  
Mutation Rate ◽  
Evolutionary Dynamics ◽  
Bacterial Species ◽  
Invasive Disease ◽  
Mutation Rates ◽  
Ecological Change ◽  
Zoonotic Pathogen ◽  
Wide Range ◽  
The Impact

Mutation rates vary both within and between bacterial species, and understanding what drives this variation is essential for understanding the evolutionary dynamics of bacterial populations. In this study, we investigate two factors that are predicted to influence the mutation rate: ecology and genome size. We conducted mutation accumulation experiments on eight strains of the emerging zoonotic pathogen Streptococcus suis. Natural variation within this species allows us to compare tonsil carriage and invasive disease isolates, from both more and less pathogenic populations, with a wide range of genome sizes. We find that invasive disease isolates have repeatedly evolved mutation rates that are higher than those of closely related carriage isolates, regardless of variation in genome size. Independent of this variation in overall rate, we also observe a stronger bias towards G/C to A/T mutations in isolates from more pathogenic populations, whose genomes tend to be smaller and more AT-rich. Our results suggest that ecology is a stronger correlate of mutation rate than genome size over these timescales, and that transitions to invasive disease are consistently accompanied by rapid increases in mutation rate. These results shed light on the impact that ecology can have on the adaptive potential of bacterial pathogens.

scholarly journals Reversion is most likely under high mutation supply, when compensatory mutations don’t fully restore fitness costs

2020 ◽  
Author(s):  
Pleuni S. Pennings ◽  
C. Brandon Ogbunugafor ◽  
Ruth Hershberg
Keyword(s):  
Mutation Rate ◽  
Experimental Evolution ◽  
Evolutionary Dynamics ◽  
Microbial Evolution ◽  
Compensatory Mutation ◽  
Adaptive Mutations ◽  
Fitness Effects ◽  
Theoretical Approaches ◽  
Evolution Study ◽  
Compensatory Mutations

AbstractAdaptive mutations are often associated with a fitness cost. These costs can be compensated for through the acquisition of additional mutations, or the adaptations can be lost through reversion, in settings where they are no longer favored. While the dynamics of adaptation, reversion and compensation have been central features in several studies of microbial evolution, few studies have attempted to resolve the population genetics underlying how and when either compensation or reversion occur. Specifically, questions remain regarding how certain actors—the evolution of mutators and whether compensatory mutations alleviate costs fully or partially—may influence evolutionary dynamics of compensation and reversion. In this study, we attempt to explain findings from an experimental evolution study by utilizing computational and theoretical approaches towards a more refined understanding of how mutation rate and the fitness effects of compensatory mutation influence evolutionary dynamics. We find that high mutation rates increase the probability of reversion of deleterious adaptations when compensation is only partial. The existence of even a single fully compensatory mutation is associated with a dramatically decreased probability of reversion. Experimental results suggest that, in some contexts, compensatory mutations are not able to fully alleviate costs associated with adaption. Our findings emphasize the role of both mutation rate and the fitness effects of compensatory mutation in crafting evolutionary dynamics, and highlight the importance of population genetic theory for explaining findings from experimental evolution.

scholarly journals Fitness landscape analysis reveals that the wild type allele is sub-optimal and mutationally robust

2021 ◽  
Author(s):  
Tzahi Gabzi ◽  
Yitzhak Tzachi Pilpel ◽  
Tamar Friedlander
Keyword(s):  
Mutation Rate ◽  
Evolutionary Biology ◽  
Evolutionary Dynamics ◽  
Fitness Landscape ◽  
Mutation Rates ◽  
Wild Type Allele ◽  
Wild Type ◽  
Type Allele ◽  
Landscape Mapping ◽  
Evolutionary Trajectories

Fitness landscape mapping and the prediction of evolutionary trajectories on these landscapes are major tasks in evolutionary biology research. Evolutionary dynamics is tightly linked to the landscape topography, but this relation is not straightforward. Models predict different evolutionary outcomes depending on mutation rates: high-fitness genotypes should dominate the population under low mutation rates and lower-fitness, mutationally robust (also called 'flat') genotypes - at higher mutation rates. Yet, so far, flat genotypes have been demonstrated in very few cases, particularly in viruses. The quantitative conditions for their emergence were studied only in simplified single-locus, two-peak landscapes. In particular, it is unclear whether within the same genome some genes can be flat while the remaining ones are fit. Here, we analyze a previously measured fitness landscape of a yeast tRNA gene. We found that the wild type allele is sub-optimal, but is mutationally robust ('flat'). Using computer simulations, we estimated the critical mutation rate in which transition from fit to flat allele should occur for a gene with such characteristics. We then used a scaling argument to extrapolate this critical mutation rate for a full genome, assuming the same mutation rate for all genes. Finally, we propose that while the majority of genes are still selected to be fittest, there are a few mutation hot-spots like the tRNA, for which the mutationally robust flat allele is favored by selection.

The Rate of Adaptation in Asexuals

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 961-968 ◽  
Author(s):  
H Allen Orr
Keyword(s):  
Mutation Rate ◽  
Chromosome Region ◽  
Deleterious Mutations ◽  
Clonal Interference ◽  
Favorable Alleles ◽  
Genetics Of Adaptation ◽  
Selection For ◽  
Probability Of Fixation ◽  
Adaptive Substitution ◽  
Rate Of Substitution

Abstract I study the population genetics of adaptation in asexuals. I show that the rate of adaptive substitution in an asexual species or nonrecombining chromosome region is a bell-shaped function of the mutation rate: at some point, increasing the mutation rate decreases the rate of substitution. Curiously, the mutation rate that maximizes the rate of adaptation depends solely on the strength of selection against deleterious mutations. In particular, adaptation is fastest when the genomic rate of mutation, U, equals the harmonic mean of selection coefficients against deleterious mutations, where we assume that selection for favorable alleles is milder than that against deleterious ones. This simple result is independent of the shape of the distribution of effects among favorable and deleterious mutations, population size, and the action of clonal interference. In the course of this work, I derive an approximation to the probability of fixation of a favorable mutation in an asexual genome or nonrecombining chromosome region in which both favorable and deleterious mutations occur.

scholarly journals Low Mutational Load Allows for High Mutation Rate Variation in Gut Commensal Bacteria

2019 ◽  
Author(s):  
Ricardo S. Ramiro ◽  
Paulo Durão ◽  
Claudia Bank ◽  
Isabel Gordo
Keyword(s):  
Gut Microbiota ◽  
Mutation Rate ◽  
Microbial Evolution ◽  
Rate Variation ◽  
Mutational Load ◽  
Deleterious Mutations ◽  
Natural Ecosystems ◽  
Fluctuating Selection ◽  
Beneficial Mutations ◽  
Mutation Rate Variation

AbstractBacteria generally live in species-rich communities, such as the gut microbiota. Yet, little is known about bacterial evolution in natural ecosystems. Here, we followed the long-term evolution of commensalEscherichia coliin the mouse gut. We observe the emergence of polymorphism for mutation rate, ranging from wild-type levels to 1000-fold higher. By combining experiments, whole-genome sequencing andin silicosimulations, we identify the molecular causes and evolutionary conditions that allow these hypermutators to emerge and coexist within a complex microbiota. The hypermutator phenotype is caused by mutations in DNA polymerase III, which increase mutation rate by ~1000-fold (a mutation in the proofreading subunit) and stabilize hypermutator fitness (mutations in the catalytic subunit). The strong mutation rate variation persists for >1000 generations, with coexistence between lineages carrying 4 to >600 mutations. Thisin vivomolecular evolution pattern is consistent with deleterious mutations of ~0.01-0.001% fitness effects, 100 to 1000-fold lower than currentin vitroestimates. Despite large numbers of deleterious mutations, we identify multiple beneficial mutations that do not reach fixation over long periods of time. This indicates that the dynamics of beneficial mutations are not shaped by constant positive Darwinian selection but by processes leading to negative frequency-dependent or temporally fluctuating selection. Thus, microbial evolution in the gut is likely characterized by partial sweeps of beneficial mutations combined with hitchhiking of very slightly deleterious mutations, which take a long time to be purged but impose a very weak mutational load. These results are consistent with the pattern of genetic polymorphism that is emerging from metagenomics studies of the human gut microbiota, suggesting that we identified key evolutionary processes shaping the genetic composition of this community.

scholarly journals Evolution of mutation rates in hypermutable populations of Escherichia coli propagated at very small effective population size

2017 ◽  
Vol 13 (3) ◽  
pp. 20160849 ◽  
Author(s):  
Tanya Singh ◽  
Meredith Hyun ◽  
Paul Sniegowski
Keyword(s):  
Escherichia Coli ◽  
Genetic Variation ◽  
Mutation Rate ◽  
Mutation Rates ◽  
Deleterious Mutations ◽  
Effective Population ◽  
Ultimate Source ◽  
Systematic Evolution ◽  
Small Effective Size ◽  
Small Effective Population Size

Mutation is the ultimate source of the genetic variation—including variation for mutation rate itself—that fuels evolution. Natural selection can raise or lower the genomic mutation rate of a population by changing the frequencies of mutation rate modifier alleles associated with beneficial and deleterious mutations. Existing theory and observations suggest that where selection is minimized, rapid systematic evolution of mutation rate either up or down is unlikely. Here, we report systematic evolution of higher and lower mutation rates in replicate hypermutable Escherichia coli populations experimentally propagated at very small effective size—a circumstance under which selection is greatly reduced. Several populations went extinct during this experiment, and these populations tended to evolve elevated mutation rates. In contrast, populations that survived to the end of the experiment tended to evolve decreased mutation rates. We discuss the relevance of our results to current ideas about the evolution, maintenance and consequences of high mutation rates.

scholarly journals Genomic mutation rates that neutralize adaptive evolution and natural selection

2013 ◽  
Vol 10 (85) ◽  
pp. 20130329 ◽  
Author(s):  
Philip J. Gerrish ◽  
Alexandre Colato ◽  
Paul D. Sniegowski
Keyword(s):  
Natural Selection ◽  
Mutation Rate ◽  
Adaptive Evolution ◽  
Detrimental Effect ◽  
A Priori ◽  
Mutation Rates ◽  
Deleterious Mutations ◽  
Previous Theory ◽  
Mathematical Expressions ◽  
Compensatory Mutations

When mutation rates are low, natural selection remains effective, and increasing the mutation rate can give rise to an increase in adaptation rate. When mutation rates are high to begin with, however, increasing the mutation rate may have a detrimental effect because of the overwhelming presence of deleterious mutations. Indeed, if mutation rates are high enough: (i) adaptive evolution may be neutralized, resulting in a zero (or negative) adaptation rate despite the continued availability of adaptive and/or compensatory mutations, or (ii) natural selection may be neutralized, because the fitness of lineages bearing adaptive and/or compensatory mutations—whether established or newly arising—is eroded by excessive mutation, causing such lineages to decline in frequency. We apply these two criteria to a standard model of asexual adaptive evolution and derive mathematical expressions—some new, some old in new guise—delineating the mutation rates under which either adaptive evolution or natural selection is neutralized. The expressions are simple and require no a priori knowledge of organism- and/or environment-specific parameters. Our discussion connects these results to each other and to previous theory, showing convergence or equivalence of the different results in most cases.

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