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 The effect of spatial structure on adaptation in Escherichia coli

2007 ◽  
Vol 4 (1) ◽  
pp. 57-59 ◽  
Author(s):  
Lilia Perfeito ◽  
M. Inês Pereira ◽  
Paulo R.A Campos ◽  
Isabel Gordo
Keyword(s):  
Escherichia Coli ◽  
Spatial Structure ◽  
Experimental Evolution ◽  
Petri Dish ◽  
Mutation Rates ◽  
Wild Type ◽  
Clonal Interference ◽  
Genetic Studies ◽  
Significant Difference ◽  
The Cost

Populations of organisms are generally organized in a given spatial structure. However, the vast majority of population genetic studies are based on populations in which every individual competes globally. Here we use experimental evolution in Escherichia coli to directly test a recently made prediction that spatial structure slows down adaptation and that this cost increases with the mutation rate. This was studied by comparing populations of different mutation rates adapting to a liquid (unstructured) medium with populations that evolved in a Petri dish on solid (structured) medium. We find that mutators adapt faster to both environments and that adaptation is slower if there is spatial structure. We observed no significant difference in the cost of structure between mutator and wild-type populations, which suggests that clonal interference is intense in both genetic backgrounds.

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 Mutation accumulation and fitness in mutator subpopulations of Escherichia coli

2013 ◽  
Vol 9 (1) ◽  
pp. 20120961 ◽  
Author(s):  
Ram P. Maharjan ◽  
Bin Liu ◽  
Yang Li ◽  
Peter R. Reeves ◽  
Lei Wang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Significant Proportion ◽  
Mutation Accumulation ◽  
Mutation Rates ◽  
Deleterious Mutations ◽  
Wild Type ◽  
Beneficial Mutations ◽  
Bacterial Populations ◽  
Neutral Mutations ◽  
Over Time

Bacterial populations in clinical and laboratory settings contain a significant proportion of mutants with elevated mutation rates (mutators). Mutators have a particular advantage when multiple beneficial mutations are needed for fitness, as in antibiotic resistance. Nevertheless, high mutation rates potentially lead to increasing numbers of deleterious mutations and subsequently to the decreased fitness of mutators. To test how fitness changed with mutation accumulation, genome sequencing and fitness assays of nine Escherichia coli mutY mutators were undertaken in an evolving chemostat population at three time points. Unexpectedly, the fitness in members of the mutator subpopulation became constant despite a growing number of mutations over time. To test if the accumulated mutations affected fitness, we replaced each of the known beneficial mutations with wild-type alleles in a mutator isolate. We found that the other 25 accumulated mutations were not deleterious. Our results suggest that isolates with deleterious mutations are eliminated by competition in a continuous culture, leaving mutators with mostly neutral mutations. Interestingly, the mutator–non-mutator balance in the population reversed after the fitness plateau of mutators was reached, suggesting that the mutator–non-mutator ratio in populations has more to do with competition between members of the population than the accumulation of deleterious mutations.

scholarly journals Adaptation, Clonal Interference, and Frequency-Dependent Interactions in a Long-Term Evolution Experiment with Escherichia coli

2015 ◽  
Author(s):  
Rohan Maddamsetti ◽  
Richard E. Lenski ◽  
Jeffrey E. Barrick
Keyword(s):  
Escherichia Coli ◽  
Frequency Dependence ◽  
Evolutionary Dynamics ◽  
Selective Sweeps ◽  
Clonal Interference ◽  
Beneficial Mutations ◽  
Frequency Dependent ◽  
Evolution Experiment ◽  
History Of

Twelve replicate populations of Escherichia coli have been evolving in the laboratory for more than 25 years and 60,000 generations. We analyzed bacteria from whole-population samples frozen every 500 generations through 20,000 generations for one well-studied population, called Ara???1. By tracking 42 known mutations in these samples, we reconstructed the history of this population???s genotypic evolution over this period. The evolutionary dynamics of Ara???1 show strong evidence of selective sweeps as well as clonal interference between competing lineages bearing different beneficial mutations. In some cases, sets of several mutations approached fixation simultaneously, often conveying no information about their order of origination; we present several possible explanations for the existence of these mutational cohorts. Against a backdrop of rapid selective sweeps both earlier and later, we found that two clades coexisted for over 6000 generations before one drove the other extinct. In that time, at least nine mutations arose in the clade that prevailed. We found evidence that the clades evolved a frequency-dependent interaction, which prevented the competitive exclusion of either clade, but which eventually collapsed as beneficial mutations accumulated in the clade that prevailed. Clonal interference and frequency dependence can occur even in the simplest microbial populations. Furthermore, frequency dependence may generate dynamics that extend the period of coexistence that would otherwise be sustained by clonal interference alone.

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.

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 Spontaneously Arising mutL Mutators in Evolving Escherichia coli Populations Are the Result of Changes in Repeat Length

2003 ◽  
Vol 185 (20) ◽  
pp. 6076-6082 ◽  
Author(s):  
Aaron C. Shaver ◽  
Paul D. Sniegowski
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Mutation Rate ◽  
Mismatch Repair Gene ◽  
Dna Repeats ◽  
Wild Type ◽  
Repair Gene ◽  
Mutator Strains ◽  
Experimental Populations

ABSTRACT Over the course of thousands of generations of growth in a glucose-limited environment, 3 of 12 experimental populations of Escherichia coli spontaneously and independently evolved greatly increased mutation rates. In two of the populations, the mutations responsible for this increased mutation rate lie in the same region of the mismatch repair gene mutL. In this region, a 6-bp repeat is present in three copies in the gene of the wild-type ancestor of the experimental populations but is present in four copies in one of the experimental populations and two copies in the other. These in-frame mutations either add or delete the amino acid sequence LA in the MutL protein. We determined that the replacement of the wild-type sequence with either of these mutations was sufficient to increase the mutation rate of the wild-type strain to a level comparable to that of the mutator strains. Complementation of strains bearing the mutator mutations with wild-type copies of either mutL or the mismatch repair gene uvrD rescued the wild-type mutation rate. The position of the mutator mutations—in the region of MutL known as the ATP lid—suggests a possible deficiency in MutL's ATPase activity as the cause of the mutator phenotype. The similarity of the two mutator mutations (despite the independent evolutionary histories of the populations that gave rise to them) leads to a discussion of the potential adaptive role of DNA repeats.

Enrichment and Elimination of mutY Mutators in Escherichia coli Populations

Genetics ◽  
2002 ◽  
Vol 162 (3) ◽  
pp. 1055-1062 ◽  
Author(s):  
Lucinda Notley-McRobb ◽  
Shona Seeto ◽  
Thomas Ferenci
Keyword(s):  
Escherichia Coli ◽  
The Other ◽  
Mutation Rates ◽  
Beneficial Mutation ◽  
Glucose Limitation ◽  
Epistatic Interactions ◽  
Beneficial Mutations ◽  
Bacterial Populations ◽  
Kinetics Of ◽  
Selection Event

Abstract The kinetics of mutator sweeps was followed in two independent populations of Escherichia coli grown for up to 350 generations in glucose-limited continuous culture. A rapid elevation of mutation rates was observed in both populations within 120-150 generations, as was apparent from major increases in the proportion of the populations with unselected mutations in fhuA. The increase in mutation rates was due to sweeps by mutY mutators. In both cultures, the enrichment of mutators resulted from hitchhiking with identified beneficial mutations increasing fitness under glucose limitation; mutY hitchhiked with mgl mutations in one culture and ptsG in the other. In both cases, mutators were enriched to constitute close to 100% of the population before a periodic selection event reduced the frequency of unselected mutations and mutators in the cultures. The high proportion of mutators persisted for 150 generations in one population but began to be eliminated within 50 generations in the other. The persistence of mutator, as well as experimental data showing that mutY bacteria were as fit as near-isogenic mutY+ bacteria in competition experiments, suggest that mutator load by deleterious mutations did not explain the rapidly diminishing proportion of mutators in the populations. The nonmutators sweeping out mutators were also unlikely to have arisen by reversion or antimutator mutations; the mutY mutations were major deletions in each case and the bacteria sweeping out mutators contained intact mutY. By following mgl allele frequencies in one population, we discovered that mutators were outcompeted by bacteria that had rare mgl mutations previously as well as additional beneficial mutation(s). The pattern of appearance of mutY, but not its elimination, conforms to current models of mutator sweeps in bacterial populations. A mutator with a narrow mutational spectrum like mutY may be lost if the requirement for beneficial mutations is for changes other than GC → TA transversions. Alternatively, epistatic interactions between mutator mutation and beneficial mutations need to be postulated to explain mutator elimination.

scholarly journals SELECTION FOR HIGH MUTATION RATES IN CHEMOSTATS

Genetics ◽  
1974 ◽  
Vol 77 (2) ◽  
pp. 169-184
Author(s):  
Edward C Cox ◽  
Thomas C Gibson
Keyword(s):  
Escherichia Coli ◽  
Population Density ◽  
Mutation Rates ◽  
Strongly Correlated ◽  
Wild Type ◽  
Selection For

ABSTRACT Competition experiments in chemostats show that mutator populations of Escherichia coli are more fit than wild type. The increased fitness can be explained by the appearance of new mutants better adapted to the chemostat environment. Fitness values vary between chemostats and are strongly correlated (P < 0.001) with fluctuations in population density.

Antimutator Mutants in Bacteriophage T4 and Escherichia coli

Genetics ◽  
1998 ◽  
Vol 148 (4) ◽  
pp. 1579-1585 ◽  
Author(s):  
Roel M Schaaper
Keyword(s):  
Escherichia Coli ◽  
Type Strain ◽  
Wild Type Strain ◽  
Bacteriophage T4 ◽  
Mutation Rates ◽  
Spontaneous Mutations ◽  
Wild Type ◽  
Mutant Strains ◽  
Distinguishing Property ◽  
Insight Into

Abstract Antimutators are mutant strains that have reduced mutation rates compared to the corresponding wild-type strain. Their existence, along with mutator mutants that have higher mutation rates compared to the wild-type strain, are powerful evidence that mutation rates are genetically controlled. Compared to mutator mutants, antimutators have a very distinguishing property. Because they prevent normally occurring mutations, they, uniquely, are capable of providing insight into the mechanisms of spontaneous mutations. In this review, antimutator mutants are discussed in bacteriophage T4 and the bacterium Escherichia coli, with regard to their properties, possible mechanisms, and implications for the sources of spontaneous mutations in these two organisms.

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