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 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 The effect of weak clonal interference on average fitness trajectories in the presence of macroscopic epistasis

2021 ◽  
Author(s):  
Yipei Guo ◽  
Ariel Amir
Keyword(s):  
Mutation Rate ◽  
Fitness Landscape ◽  
Large Population ◽  
Beneficial Mutation ◽  
Clonal Interference ◽  
Beneficial Mutations ◽  
Speed Up ◽  
Fixation Probabilities ◽  
Population Competition ◽  
Open Question

Adaptation dynamics on fitness landscapes is often studied theoretically in the strong-selection, weak-mutation (SSWM) regime. However, in a large population, multiple beneficial mutants can emerge before any of them fixes in the population. Competition between mutants is known as clonal interference, and how it affects the form of long-term fitness trajectories in the presence of epistasis is an open question. Here, by considering how changes in fixation probabilities arising from weak clonal interference affect the dynamics of adaptation on fitness-parameterized landscapes, we find that the change in the form of fitness trajectory arises only through changes in the supply of beneficial mutations (or equivalently, the beneficial mutation rate). Furthermore, a depletion of beneficial mutations as a population climbs up the fitness landscape can speed up the functional form of the fitness trajectory, while an enhancement of the beneficial mutation rate does the opposite of slowing down the form of the dynamics. Our findings suggest that by carrying out evolution experiments in both regimes (with and without clonal interference), one could potentially distinguish the different sources of macroscopic epistasis (fitness effect of mutations vs. change in fraction of 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 Mutation Rate Inferred From Synonymous Substitutions in a Long-Term Evolution Experiment With Escherichia coli

2011 ◽  
Vol 1 (3) ◽  
pp. 183-186 ◽  
Author(s):  
Sébastien Wielgoss ◽  
Jeffrey E. Barrick ◽  
Olivier Tenaillon ◽  
Stéphane Cruveiller ◽  
Béatrice Chane-Woon-Ming ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mutation Rate ◽  
Long Term Evolution ◽  
Synonymous Substitutions ◽  
Term Evolution ◽  
Evolution Experiment

scholarly journals Effect of Repeat Copy Number on Variable-Number Tandem Repeat Mutations in Escherichia coli O157:H7

2006 ◽  
Vol 188 (12) ◽  
pp. 4253-4263 ◽  
Author(s):  
Amy J. Vogler ◽  
Christine Keys ◽  
Yoshimi Nemoto ◽  
Rebecca E. Colman ◽  
Zack Jay ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Mutation Rate ◽  
Tandem Repeat ◽  
Copy Number ◽  
Variable Number Tandem Repeat ◽  
Variable Number ◽  
Mutation Rates ◽  
Repeat Copy Number ◽  
Repeat Copy

ABSTRACT Variable-number tandem repeat (VNTR) loci have shown a remarkable ability to discriminate among isolates of the recently emerged clonal pathogen Escherichia coli O157:H7, making them a very useful molecular epidemiological tool. However, little is known about the rates at which these sequences mutate, the factors that affect mutation rates, or the mechanisms by which mutations occur at these loci. Here, we measure mutation rates for 28 VNTR loci and investigate the effects of repeat copy number and mismatch repair on mutation rate using in vitro-generated populations for 10 E. coli O157:H7 strains. We find single-locus rates as high as 7.0 × 10−4 mutations/generation and a combined 28-locus rate of 6.4 × 10−4 mutations/generation. We observed single- and multirepeat mutations that were consistent with a slipped-strand mispairing mutation model, as well as a smaller number of large repeat copy number mutations that were consistent with recombination-mediated events. Repeat copy number within an array was strongly correlated with mutation rate both at the most mutable locus, O157-10 (r 2 = 0.565, P = 0.0196), and across all mutating loci. The combined locus model was significant whether locus O157-10 was included (r 2 = 0.833, P < 0.0001) or excluded (r 2 = 0.452, P < 0.0001) from the analysis. Deficient mismatch repair did not affect mutation rate at any of the 28 VNTRs with repeat unit sizes of >5 bp, although a poly(G) homomeric tract was destabilized in the mutS strain. Finally, we describe a general model for VNTR mutations that encompasses insertions and deletions, single- and multiple-repeat mutations, and their relative frequencies based upon our empirical mutation rate data.

scholarly journals Diverse phenotypic and genetic responses to short-term selection in evolving Escherichia coli populations

2015 ◽  
Author(s):  
Marcus M Dillon ◽  
Nicholas P Rouillard ◽  
Brian Van Dam ◽  
Romain Gallet ◽  
Vaughn S Cooper
Keyword(s):  
Escherichia Coli ◽  
Fitness Landscape ◽  
Single Point ◽  
Beneficial Mutations ◽  
True Nature ◽  
Term Selection ◽  
Adaptive Mutations ◽  
Fitness Effects ◽  
Genetic Responses

Beneficial mutations fuel adaptation by altering phenotypes that enhance the fit of organisms to their environment. However, the phenotypic effects of mutations often depend on ecological context, making the distribution of effects across multiple environments essential to understanding the true nature of beneficial mutations. Studies that address both the genetic basis and ecological consequences of adaptive mutations remain rare. Here, we characterize the direct and pleiotropic fitness effects of a collection of 21 first-step beneficial mutants derived from naive and adapted genotypes used in a long-term experimental evolution of Escherichia coli. Whole-genome sequencing was used to identify most beneficial mutations. In contrast to previous studies, we find diverse fitness effects of mutations selected in a simple environment and few cases of genetic parallelism. The pleiotropic effects of these mutations were predominantly positive but some mutants were highly antagonistic in alternative environments. Further, the fitness effects of mutations derived from the adapted genotypes were dramatically reduced in nearly all environments. These findings suggest that many beneficial variants are accessible from a single point on the fitness landscape, and the fixation of alternative beneficial mutations may have dramatic consequences for niche breadth reduction via metabolic erosion.

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.

scholarly journals Divergent evolution of mutation rates and biases in the long-term evolution experiment with Escherichia coli

2020 ◽  
Author(s):  
Rohan Maddamsetti ◽  
Nkrumah A. Grant
Keyword(s):  
Escherichia Coli ◽  
Point Mutations ◽  
Long Term Evolution ◽  
Dna Topology ◽  
Mutation Rates ◽  
Rate Variation ◽  
Historical Contingency ◽  
Term Evolution ◽  
Evolution Experiment

ABSTRACTAll organisms encode enzymes that replicate, maintain, pack, recombine, and repair their genetic material. For this reason, mutation rates and biases also evolve by mutation, variation, and natural selection. By examining metagenomic time series of the Lenski long-term evolution experiment (LTEE) with Escherichia coli (Good, et al. 2017), we find that local mutation rate variation has evolved during the LTEE. Each LTEE population has evolved idiosyncratic differences in their rates of point mutations, indels, and mobile element insertions, due to the fixation of various hypermutator and antimutator alleles. One LTEE population, called Ara+3, shows a strong, symmetric wave pattern in its density of point mutations, radiating from the origin of replication. This pattern is largely missing from the other LTEE populations, most of which evolved missense, indel, or structural mutations in topA, fis, and dusB— loci that all affect DNA topology. The distribution of mutations in those genes over time suggests epistasis and historical contingency in the evolution of DNA topology, which may have in turn affected local mutation rates. Overall, the replicate populations of the LTEE have largely diverged in their mutation rates and biases, even though they have adapted to identical abiotic conditions.

scholarly journals Tempo and mode of genome evolution in a 50,000-generation experiment

2016 ◽  
Author(s):  
Olivier Tenaillon ◽  
Jeffrey E. Barrick ◽  
Noah Ribeck ◽  
Daniel E. Deatherage ◽  
Jeffrey L. Blanchard ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Genome Evolution ◽  
Mutation Rate ◽  
Beneficial Mutations ◽  
Insertions And Deletions ◽  
Constant Rate ◽  
Shifting Balance ◽  
Balance Of Forces ◽  
Neutral Mutations

Adaptation depends on the rates, effects, and interactions of many mutations. We analyzed 264 genomes from 12 Escherichia coli populations to characterize their dynamics over 50,000 generations. The trajectories for genome evolution in populations that retained the ancestral mutation rate fit a model where most fixed mutations are beneficial, the fraction of beneficial mutations declines as fitness rises, and neutral mutations accumulate at a constant rate. We also compared these populations to lines evolved under a mutation-accumulation regime that minimizes selection. Nonsynonymous mutations, intergenic mutations, insertions, and deletions are overrepresented in the long-term populations, supporting the inference that most fixed mutations are favored by selection. These results illuminate the shifting balance of forces that govern genome evolution in populations adapting to a new environment.

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.

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