scholarly journals Dynamics and fate of beneficial mutations under lineage contamination by linked deleterious mutations

2016 ◽  
Author(s):  
Sophie Pénisson ◽  
Tanya Singh ◽  
Paul Sniegowski ◽  
Philip Gerrish
Keyword(s):  
Mutation Rate ◽  
Branching Process ◽  
Deleterious Mutation ◽  
Selective Advantage ◽  
Single Type ◽  
Deleterious Mutations ◽  
Beneficial Mutations ◽  
Multitype Branching Process ◽  
Fitness Effects ◽  
Adaptive Substitution

ABSTRACTBeneficial mutations drive adaptive evolution, yet their selective advantage does not ensure their fixation. Haldane’s application of single-type branching process theory showed that genetic drift alone could cause the extinction of newly-arising beneficial mutations with high probability. With linkage, deleterious mutations will affect the dynamics of beneficial mutations and might further increase their extinction probability. Here, we model the lineage dynamics of a newly-arising beneficial mutation as a multitype branching process; this approach allows us to account for the combined effects of drift and the stochastic accumulation of linked deleterious mutations, which we call lineage contamination. We first study the lineage contamination phenomenon in isolation, deriving extinction times and probabilities of beneficial lineages. We then put the lineage contamination phenomenon into the context of an evolving population by incorporating the effects of background selection. We find that the survival probability of beneficial mutations is simply Haldane’s classical formula multiplied by the correction factor , where U is deleterious mutation rate, is mean selective advantage of beneficial mutations, κ ∈ (1, ε], and ε = 2 – e−1. We also find there exists a genomic deleterious mutation rate, , that maximizes the rate of production of surviving beneficial mutations, and that . Both of these results, and others, are curiously independent of the fitness effects of deleterious mutations. We derive critical mutation rates above which: 1) lineage contamination alleviates competition among beneficial mutations, and 2) the adaptive substitution process all but shuts down.

scholarly journals A Branching Process Model of Evolutionary Rescue

2021 ◽  
Author(s):  
Peter Olofsson ◽  
Ricardo B. R. Azevedo
Keyword(s):  
Population Growth ◽  
Mutation Rate ◽  
Discrete Time ◽  
Growth Curve ◽  
Process Model ◽  
Branching Process ◽  
Selective Advantage ◽  
Population Declines ◽  
Beneficial Mutations ◽  
Evolutionary Rescue

Evolutionary rescue is the process whereby a declining population may start growing again, thus avoiding extinction, via an increase in the frequency of beneficial genotypes. These genotypes may either already be present in the population in small numbers, or arise by mutation as the population declines. We present a simple two-type discrete-time branching process model and use it to obtain results such as the probability of rescue, the shape of the population growth curve of a rescued population, and the time until the first rescuing mutation occurs. Comparisons are made to existing results in the literature in cases where both the mutation rate and the selective advantage of the beneficial mutations are small.

scholarly journals Inference of distribution of fitness effects and proportion of adaptive substitutions from polymorphism data

2016 ◽  
Author(s):  
Paula Tataru ◽  
Maéva Mollion ◽  
Sylvain Glemin ◽  
Thomas Bataillon
Keyword(s):  
Molecular Evolution ◽  
Evolutionary Genetics ◽  
Deleterious Mutations ◽  
Probabilistic Framework ◽  
Evolutionary Trajectory ◽  
Beneficial Mutations ◽  
Fitness Effects ◽  
Polymorphism Data ◽  
Inference Methods ◽  
Biased Estimates

ABSTRACTThe distribution of fitness effects (DFE) encompasses deleterious, neutral and beneficial mutations. It conditions the evolutionary trajectory of populations, as well as the rate of adaptive molecular evolution (α). Inference of DFE and α from patterns of polymorphism (SFS) and divergence data has been a longstanding goal of evolutionary genetics. A widespread assumption shared by numerous methods developed so far to infer DFE and α from such data is that beneficial mutations contribute only negligibly to the polymorphism data. Hence, a DFE comprising only deleterious mutations tends to be estimated from SFS data, and α is only predicted by contrasting the SFS with divergence data from an outgroup. Here, we develop a hierarchical probabilistic framework that extends on previous methods and also can infer DFE and α from polymorphism data alone. We use extensive simulations to examine the performance of our method. We show that both a full DFE, comprising both deleterious and beneficial mutations, and α can be inferred without resorting to divergence data. We demonstrate that inference of DFE from polymorphism data alone can in fact provide more reliable estimates, as it does not rely on strong assumptions about a shared DFE between the outgroup and ingroup species used to obtain the SFS and divergence data. We also show that not accounting for the contribution of beneficial mutations to polymorphism data leads to substantially biased estimates of the DFE and α. We illustrate these points using our newly developed framework, while also comparing to one of the most widely used inference methods available.

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 The Effect of Overdominance on Characterizing Deleterious Mutations in Large Natural Populations

Genetics ◽  
1999 ◽  
Vol 151 (2) ◽  
pp. 895-913 ◽  
Author(s):  
Jin-Long Li ◽  
Jian Li ◽  
Hong-Wen Deng
Keyword(s):  
Genetic Variation ◽  
Mutation Rate ◽  
Deleterious Mutation ◽  
Natural Populations ◽  
Mutation Accumulation ◽  
Statistical Properties ◽  
Alternative Methods ◽  
Deleterious Mutations ◽  
Selection Coefficient ◽  
New Approaches

Abstract Alternatives to the mutation-accumulation approach have been developed to characterize deleterious genomic mutations. However, they all depend on the assumption that the standing genetic variation in natural populations is solely due to mutation-selection (M-S) balance and therefore that overdominance does not contribute to heterosis. Despite tremendous efforts, the extent to which this assumption is valid is unknown. With different degrees of violation of the M-S balance assumption in large equilibrium populations, we investigated the statistical properties and the robustness of these alternative methods in the presence of overdominance. We found that for dominant mutations, estimates for U (genomic mutation rate) will be biased upward and those for h̄ (mean dominance coefficient) and s̄ (mean selection coefficient), biased downward when additional overdominant mutations are present. However, the degree of bias is generally moderate and depends largely on the magnitude of the contribution of overdominant mutations to heterosis or genetic variation. This renders the estimates of U and s̄ not always biased under variable mutation effects that, when working alone, cause U and s̄ to be underestimated. The contributions to heterosis and genetic variation from overdominant mutations are monotonic but not linearly proportional to each other. Our results not only provide a basis for the correct inference of deleterious mutation parameters from natural populations, but also alleviate the biggest concern in applying the new approaches, thus paving the way for reliably estimating properties of deleterious mutations.

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 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 Evolutionary consequences of mutation and selection within an individual.

Genetics ◽  
1995 ◽  
Vol 141 (3) ◽  
pp. 1173-1187 ◽  
Author(s):  
S P Otto ◽  
M E Orive
Keyword(s):  
Mutation Rate ◽  
Deleterious Mutation ◽  
Cell Lineage ◽  
Deleterious Mutations ◽  
Cell Replication ◽  
Mutation Load ◽  
Ploidy Levels ◽  
Cell Lineages ◽  
Evolutionary Consequences ◽  
Mutant Cells

Abstract Whether in sexual or asexual organisms, selection among cell lineages during development is an effective way of eliminating deleterious mutations. Using a mathematical analysis, we find that relatively small differences in cell replication rates during development can translate into large differences in the proportion of mutant cells within the adult, especially when development involves a large number of cell divisions. Consequently, intraorganismal selection can substantially reduce the deleterious mutation rate observed among offspring as well as the mutation load within a population, because cells rather than individuals provide the selective "deaths" necessary to stem the tide of deleterious mutations. The reduction in mutation rate among offspring is more pronounced in organisms with plastic development than in those with structured development. It is also more pronounced in asexual organisms that produce multicellular rather than unicellular offspring. By effecting the mutation rate, intraorganismal selection may have broad evolutionary implications; as an example, we consider its influence on the evolution of ploidy levels, finding that cell-lineage selection is more effective in haploids and tends to favor their evolution.

scholarly journals Rate and effects of spontaneous mutations that affect fitness in mutator Escherichia coli

2010 ◽  
Vol 365 (1544) ◽  
pp. 1177-1186 ◽  
Author(s):  
Sandra Trindade ◽  
Lilia Perfeito ◽  
Isabel Gordo
Keyword(s):  
Escherichia Coli ◽  
Mutation Rate ◽  
Deleterious Mutation ◽  
Natural Populations ◽  
Estimation Methods ◽  
Single Individual ◽  
Deleterious Mutations ◽  
Spontaneous Mutations ◽  
Mutator Strain ◽  
Mean Fitness

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 .

scholarly journals On the Rate and Linearity of Viability Declines in Drosophila Mutation-Accumulation Experiments: Genomic Mutation Rates and Synergistic Epistasis Revisited

Genetics ◽  
2004 ◽  
Vol 166 (2) ◽  
pp. 797-806 ◽  
Author(s):  
James D Fry
Keyword(s):  
Mutation Rate ◽  
Average Rate ◽  
Natural Populations ◽  
Mutation Accumulation ◽  
High Rate ◽  
Deleterious Mutations ◽  
Order Of Magnitude ◽  
Contamination Event ◽  
Genomic Mutation ◽  
The 1960S

Abstract High rates of deleterious mutations could severely reduce the fitness of populations, even endangering their persistence; these effects would be mitigated if mutations synergize each others’ effects. An experiment by Mukai in the 1960s gave evidence that in Drosophila melanogaster, viability-depressing mutations occur at the surprisingly high rate of around one per zygote and that the mutations interact synergistically. A later experiment by Ohnishi seemed to support the high mutation rate, but gave no evidence for synergistic epistasis. Both of these studies, however, were flawed by the lack of suitable controls for assessing viability declines of the mutation-accumulation (MA) lines. By comparing homozygous viability of the MA lines to simultaneously estimated heterozygous viability and using estimates of the dominance of mutations in the experiments, I estimate the viability declines relative to an appropriate control. This approach yields two unexpected conclusions. First, in Ohnishi’s experiment as well as in Mukai’s, MA lines showed faster-than-linear declines in viability, indicative of synergistic epistasis. Second, while Mukai’s estimate of the genomic mutation rate is supported, that from Ohnishi’s experiment is an order of magnitude lower. The different results of the experiments most likely resulted from differences in the starting genotypes; even within Mukai’s experiment, a subset of MA lines, which I argue probably resulted from a contamination event, showed much slower viability declines than did the majority of lines. Because different genotypes may show very different mutational behavior, only studies using many founding genotypes can determine the average rate and distribution of effects of mutations relevant to natural populations.

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