scholarly journals The effect of known mutator alleles in a cluster of clinicalSaccharomyces cerevisiaestrains

2016 ◽  
Author(s):  
Daniel A. Skelly ◽  
Paul M. Magwene ◽  
Brianna Meeks ◽  
Helen A. Murphy
Keyword(s):  
Mutation Rate ◽  
Evolutionary Theory ◽  
Phylogenetic Analyses ◽  
Mutation Rates ◽  
Genetic Modifiers ◽  
Beneficial Mutations ◽  
Mutator Allele ◽  
Genomic Mutation ◽  
Asexual Populations ◽  
The Relationship

AbstractNatural selection has the potential to act on all phenotypes, including genomic mutation rate. Classic evolutionary theory predicts that in asexual populations, mutator alleles, which cause high mutation rates, can fix due to linkage with beneficial mutations. This phenomenon has been demonstrated experimentally and may explain the frequency of mutators found in bacterial pathogens. In contrast, in sexual populations, recombination decouples mutator alleles from beneficial mutations, preventing mutator fixation. In the facultatively sexual yeastSaccharomyces cerevisiae, segregating alleles ofMLH1andPMS1have been shown to be incompatible, causing a high mutation rate when combined. These alleles had never been found together naturally, but were recently discovered in a cluster of clinical isolates. Here we report that the incompatible mutator allele combination only marginally elevates mutation rate in these clinical strains. Genomic and phylogenetic analyses provide no evidence of a historically elevated mutation rate. We conclude that the effect of the mutator alleles is dampened by background genetic modifiers. Thus, the relationship between mutation rate and microbial pathogenicity may be more complex than once thought. Our findings provide rare observational evidence that supports evolutionary theory suggesting that sexual organisms are unlikely to harbor alleles that increase their genomic mutation rate.

scholarly journals Known mutator alleles do not markedly increase mutation rate in clinical Saccharomyces cerevisiae strains

2017 ◽  
Vol 284 (1852) ◽  
pp. 20162672 ◽  
Author(s):  
Daniel A. Skelly ◽  
Paul M. Magwene ◽  
Brianna Meeks ◽  
Helen A. Murphy
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mutation Rate ◽  
Evolutionary Theory ◽  
Phylogenetic Analyses ◽  
Genetic Modifiers ◽  
Beneficial Mutations ◽  
Mutator Allele ◽  
Genomic Mutation ◽  
Asexual Populations ◽  
The Relationship

Natural selection has the potential to act on all phenotypes, including genomic mutation rate. Classic evolutionary theory predicts that in asexual populations, mutator alleles, which cause high mutation rates, can fix due to linkage with beneficial mutations. This phenomenon has been demonstrated experimentally and may explain the frequency of mutators found in bacterial pathogens. By contrast, in sexual populations, recombination decouples mutator alleles from beneficial mutations, preventing mutator fixation. In the facultatively sexual yeast Saccharomyces cerevisiae , segregating alleles of MLH1 and PMS1 have been shown to be incompatible, causing a high mutation rate when combined. These alleles had never been found together naturally, but were recently discovered in a cluster of clinical isolates. Here we report that the incompatible mutator allele combination only marginally elevates mutation rate in these clinical strains. Genomic and phylogenetic analyses provide no evidence of a historically elevated mutation rate. We conclude that the effect of the mutator alleles is dampened by background genetic modifiers. Thus, the relationship between mutation rate and microbial pathogenicity may be more complex than once thought. Our findings provide rare observational evidence that supports evolutionary theory suggesting that sexual organisms are unlikely to harbour alleles that increase their genomic mutation rate.

scholarly journals Competition between high- and higher-mutating strains of Escherichia coli

2011 ◽  
Vol 7 (3) ◽  
pp. 422-424 ◽  
Author(s):  
Christopher F. Gentile ◽  
Szi-Chieh Yu ◽  
Sebastian Akle Serrano ◽  
Philip J. Gerrish ◽  
Paul D. Sniegowski
Keyword(s):  
Escherichia Coli ◽  
Mutation Rate ◽  
Experimental Studies ◽  
Recent Theory ◽  
Wild Type ◽  
Asexual Population ◽  
Beneficial Mutations ◽  
Experimental Support ◽  
Mutator Allele ◽  
Asexual Populations

Experimental studies have shown that a mutator allele can readily hitchhike to fixation with beneficial mutations in an asexual population having a low, wild-type mutation rate. Here, we show that a genotype bearing two mutator alleles can supplant a population already fixed for one mutator allele. Our results provide experimental support for recent theory predicting that mutator alleles will tend to accumulate in asexual populations by hitchhiking with beneficial mutations, causing an ever-higher genomic mutation rate.

scholarly journals HIGH MUTABILITY IN MALE HYBRIDS OF DROSOPHILA MELANOGASTER

Genetics ◽  
1980 ◽  
Vol 96 (2) ◽  
pp. 479-490 ◽  
Author(s):  
Michael J Simmons ◽  
Nancy A Johnson ◽  
Thomas M Fahey ◽  
Sue M Nellett ◽  
John D Raymond
Keyword(s):  
Drosophila Melanogaster ◽  
Mutation Rate ◽  
Reciprocal Cross ◽  
Mutation Rates ◽  
Mutation Induction ◽  
Hybrid Male ◽  
Lethal Mutations ◽  
The Cross ◽  
The Relationship ◽  
Reciprocal Mating

ABSTRACT The frequencies of sex-linked lethal mutations arising in hybrid male offspring from various crosses and in nonhybrid controls were determined. The hybrids were produced by crossing representative strains of the P-M system of hybrid dysgenesis in all possible combinations. Males from the cross of P males × M females had a mutation rate about 15 times higher than that of nonhybrid males from the P strain. Genetically identical males from the reciprocal cross had a mutation rate 3 to 4 times that of the nonhybrids. For crosses involving a Q strain, a significant increase in the mutation rate was detected in males produced by matings of Q males with M females. No increase was observed in genetically identical males from the reciprocal mating. Crosses between P and Q strains gave male hybrids with mutation rates not different from those of nonhybrids. Many of the lethals that occurred in hybrids from the cross of P males × M females appeared to be unstable; fewer lethals that arose in hybrids from the cross of Q males × M females were unstable. The relationship between P and Q strains is discussed with respect to a model of mutation induction in dysgenic hybrids.

scholarly journals Escherichia coli with a Tunable Point Mutation Rate for Evolution Experiments

2020 ◽  
Vol 10 (8) ◽  
pp. 2671-2681 ◽  
Author(s):  
Nicholas A. Sherer ◽  
Thomas E. Kuhlman
Keyword(s):  
Escherichia Coli ◽  
Point Mutation ◽  
Mutation Rate ◽  
Fitness Landscape ◽  
Genetically Engineered ◽  
Mutation Rates ◽  
Nucleotide Polymorphisms ◽  
Beneficial Mutations ◽  
Beneficial Effects ◽  
Evolution Experiment

The mutation rate and mutations’ effects on fitness are crucial to evolution. Mutation rates are under selection due to linkage between mutation rate modifiers and mutations’ effects on fitness. The linkage between a higher mutation rate and more beneficial mutations selects for higher mutation rates, while the linkage between a higher mutation rate and more deleterious mutations selects for lower mutation rates. The net direction of selection on mutations rates depends on the fitness landscape, and a great deal of work has elucidated the fitness landscapes of mutations. However, tests of the effect of varying a mutation rate on evolution in a single organism in a single environment have been difficult. This has been studied using strains of antimutators and mutators, but these strains may differ in additional ways and typically do not allow for continuous variation of the mutation rate. To help investigate the effects of the mutation rate on evolution, we have genetically engineered a strain of Escherichia coli with a point mutation rate that can be smoothly varied over two orders of magnitude. We did this by engineering a strain with inducible control of the mismatch repair proteins MutH and MutL. We used this strain in an approximately 350 generation evolution experiment with controlled variation of the mutation rate. We confirmed the construct and the mutation rate were stable over this time. Sequencing evolved strains revealed a higher number of single nucleotide polymorphisms at higher mutations rates, likely due to either the beneficial effects of these mutations or their linkage to beneficial mutations.

Fitness Evolution and the Rise of Mutator Alleles in Experimental Escherichia coli Populations

Genetics ◽  
2002 ◽  
Vol 162 (2) ◽  
pp. 557-566 ◽  
Author(s):  
Aaron C Shaver ◽  
Peter G Dombrowski ◽  
Joseph Y Sweeney ◽  
Tania Treis ◽  
Renata M Zappala ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Genetic Drift ◽  
Mutation Rates ◽  
Significant Gain ◽  
Wild Type ◽  
Clonal Interference ◽  
Beneficial Mutations ◽  
Mutator Allele ◽  
Experimental Populations ◽  
Rate Of Substitution

Abstract We studied the evolution of high mutation rates and the evolution of fitness in three experimental populations of Escherichia coli adapting to a glucose-limited environment. We identified the mutations responsible for the high mutation rates and show that their rate of substitution in all three populations was too rapid to be accounted for simply by genetic drift. In two of the populations, large gains in fitness relative to the ancestor occurred as the mutator alleles rose to fixation, strongly supporting the conclusion that mutator alleles fixed by hitchhiking with beneficial mutations at other loci. In one population, no significant gain in fitness relative to the ancestor occurred in the population as a whole while the mutator allele rose to fixation, but a substantial and significant gain in fitness occurred in the mutator subpopulation as the mutator neared fixation. The spread of the mutator allele from rarity to fixation took >1000 generations in each population. We show that simultaneous adaptive gains in both the mutator and wild-type subpopulations (clonal interference) retarded the mutator fixation in at least one of the populations. We found little evidence that the evolution of high mutation rates accelerated adaptation in these populations.

scholarly journals Distinct evolutionary trajectories in asexual populations through an interplay of their size, resource availability and mutation rates

2020 ◽  
Author(s):  
Bhaskar Kumawat ◽  
Ramray Bhat
Keyword(s):  
Mutation Rate ◽  
Single Cells ◽  
Maximum Size ◽  
Mutation Rates ◽  
Genome Replication ◽  
Sequence Motifs ◽  
Complex Picture ◽  
Distinct Sequence ◽  
Resource Levels ◽  
Asexual Populations

AbstractAsexually reproducing populations of single cells evolve through mutation, natural selection, and genetic drift to enhance their reproductive fitness. The environment provides the contexts that allow and regulate their fitness dynamics. In this work, we used Avida - a digital evolution framework - to uncover the effect of mutation rates, maximum size of the population, and the relative abundance of resources, on evolutionary outcomes in asexually reproducing populations of digital organisms. We observed that over extended simulations, the population evolved predominantly to one of several discrete fitness classes, each with distinct sequence motifs and/or phenotypes. For a low mutation rate, the organisms acquired either of four fitness values through an enhancement in the rate of genomic replication. Evolution at a relatively higher mutation rate presented a more complex picture. While the highest fitness values at a high mutation rate were achieved through enhanced genome replication rates, a suboptimal one was achieved through organisms sharing information relevant to metabolic tasks with each other. The information sharing capacity was vital to fitness acquisition and frequency of the genotype associated with it increased with greater resource levels and maximum population size. In addition, populations optimizing their fitness through such means exhibited a greater degree of genotypic heterogeneity and metabolic activity than those that improved replication rates. Our results reveal a minimal set of conditions for the emergence of interdependence within evolving populations with significant implications for biological systems in appropriate environmental contexts.

Meiosis and the Evolution of Recombination at Low Mutation Rates

Genetics ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 449-456 ◽  
Author(s):  
Damian D G Gessler ◽  
Shizhong Xu
Keyword(s):  
Dna Damage ◽  
Linkage Disequilibrium ◽  
Mutation Rate ◽  
Large Population ◽  
Mutation Rates ◽  
Selective Agent ◽  
Dna Mutation ◽  
Neutral Gene ◽  
Per Se ◽  
Asexual Populations

Abstract The classical understanding of recombination is that in large asexual populations with multiplicative fitness, linkage disequilibrium is negligible, and thus there is no selective agent driving an allele for recombination. This has led researchers to recognize the importance of synergistic epistatic selection in generating negative linkage disequilibrium that thereby renders an advantage to recombination. Yet data on such selection is equivocal, and various works have shown that synergistic epistasis per se, when left unquantified in its magnitude or operation, is not sufficient to drive the evolution of recombination. Here we show that neither it, nor any mechanism generating negative linkage disequilibrium among fitness-related loci, is necessary. We demonstrate that a neutral gene for recombination can increase in frequency in a large population under a low mutation rate and strict multiplicative fitness. We work in a parameter range where individuals have, on average, less than one mutation each, yet recombination can still evolve. We demonstrate this in two ways: first, by examining the consequences of recombination correlated with misrepaired DNA damage and, second, by increasing the probability of recombination with declining fitness. Interestingly, the allele spreads without repairing even a single DNA mutation.

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.

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