Recombination Speeds Adaptation by Reducing Competition between Beneficial Mutations in Populations of Escherichia coli

Cells consist of molecular modules which perform vital biological functions. Cellular modules are key units of adaptive evolution because organismal fitness depends on their performance. Theory shows that in rapidly evolving populations, such as those of many microbes, adaptation is driven primarily by common beneficial mutations with large effects, while other mutations behave as if they are effectively neutral. As a consequence, if a module can be improved only by rare and/or weak beneficial mutations, its adaptive evolution would stall. However, such evolutionary stalling has not been empirically demonstrated, and it is unclear to what extent stalling may limit the power of natural selection to improve modules. Here we empirically characterize how natural selection improves the translation machinery (TM), an essential cellular module. We experimentally evolved populations ofEscherichia coliwith genetically perturbed TMs for 1,000 generations. Populations with severe TM defects initially adapted via mutations in the TM, but TM adaptation stalled within about 300 generations. We estimate that the genetic load in our populations incurred by residual TM defects ranges from 0.5 to 19%. Finally, we found evidence that both epistasis and the depletion of the pool of beneficial mutations contributed to evolutionary stalling. Our results suggest that cellular modules may not be fully optimized by natural selection despite the availability of adaptive mutations.

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

10.1101/017020 ◽

2015 ◽

Cited By ~ 1

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.

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Genomic Identification of a Novel Mutation in hfq That Provides Multiple Benefits in Evolving Glucose-Limited Populations of Escherichia coli

Journal of Bacteriology ◽

10.1128/jb.00368-10 ◽

2010 ◽

Vol 192 (17) ◽

pp. 4517-4521 ◽

Cited By ~ 20

Author(s):

Ram Maharjan ◽

Zhemin Zhou ◽

Yan Ren ◽

Yang Li ◽

Joël Gaffé ◽

...

Keyword(s):

Escherichia Coli ◽

Novel Mutation ◽

Single Mutation ◽

Glucose Limitation ◽

Beneficial Mutations

ABSTRACT Beneficial mutations in diversifying glucose-limited Escherichia coli populations are mostly unidentified. The genome of an evolved isolate with multiple differences from that of the ancestor was fully assembled. Remarkably, a single mutation in hfq was responsible for the multiple benefits under glucose limitation through changes in at least five regulation targets.

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PLEIOTROPIC EFFECTS OF BENEFICIAL MUTATIONS IN ESCHERICHIA COLI

Evolution ◽

10.1554/05-116.1 ◽

2005 ◽

Vol 59 (11) ◽

pp. 2343 ◽

Cited By ~ 3

Author(s):

Elizabeth A. Ostrowski ◽

Daniel E. Rozen ◽

Richard E. Lenski

Keyword(s):

Escherichia Coli ◽

Pleiotropic Effects ◽

Beneficial Mutations

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Escherichia coli with a Tunable Point Mutation Rate for Evolution Experiments

G3 Genes|Genome|Genetics ◽

10.1534/g3.120.401124 ◽

2020 ◽

Vol 10 (8) ◽

pp. 2671-2681 ◽

Cited By ~ 1

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.

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Faculty Opinions recommendation of Pleiotropic effects of beneficial mutations in Escherichia coli.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1030430.358621 ◽

2006 ◽

Author(s):

Joel Kingsolver

Keyword(s):

Escherichia Coli ◽

Pleiotropic Effects ◽

Beneficial Mutations

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

Genetics ◽

10.1093/genetics/162.2.557 ◽

2002 ◽

Vol 162 (2) ◽

pp. 557-566 ◽

Cited By ~ 5

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.

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Benefits of a Recombination-Proficient Escherichia coli System for Adaptive Laboratory Evolution

Applied and Environmental Microbiology ◽

10.1128/aem.01850-16 ◽

2016 ◽

Vol 82 (22) ◽

pp. 6736-6747 ◽

Cited By ~ 10

Author(s):

George Peabody ◽

James Winkler ◽

Weston Fountain ◽

David A. Castro ◽

Enzo Leiva-Aravena ◽

...

Keyword(s):

Escherichia Coli ◽

Strong Support ◽

Mutational Load ◽

Adaptive Laboratory Evolution ◽

Beneficial Mutations ◽

Laboratory Evolution ◽

Content Type ◽

Sexual Recombination ◽

Simple Kinetic Model ◽

Neutral Mutations

ABSTRACTAdaptive laboratory evolution typically involves the propagation of organisms asexually to select for mutants with the desired phenotypes. However, asexual evolution is prone to competition among beneficial mutations (clonal interference) and the accumulation of hitchhiking and neutral mutations. The benefits of horizontal gene transfer toward overcoming these known disadvantages of asexual evolution were characterized in a strain ofEscherichia coliengineered for superior sexual recombination (genderless). Specifically, we experimentally validated the capacity of the genderless strain to reduce the mutational load and recombine beneficial mutations. We also confirmed that inclusion of multiple origins of transfer influences both the frequency of genetic exchange throughout the chromosome and the linkage of donor DNA. We built a simple kinetic model to estimate recombination frequency as a function of transfer size and relative genotype enrichment in batch transfers; the model output correlated well with the experimental data. Our results provide strong support for the advantages of utilizing the genderless strain over its asexual counterpart during adaptive laboratory evolution for generating beneficial mutants with reduced mutational load.IMPORTANCEOver 80 years ago Fisher and Muller began a debate on the origins of sexual recombination. Although many aspects of sexual recombination have been examined at length, experimental evidence behind the behaviors of recombination in many systems and the means to harness it remain elusive. In this study, we sought to experimentally validate some advantages of recombination in typically asexualEscherichia coliand determine if a sexual strain ofE. colican become an effective tool for strain development.

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Genetic background affects epistatic interactions between two beneficial mutations

Biology Letters ◽

10.1098/rsbl.2012.0328 ◽

2013 ◽

Vol 9 (1) ◽

pp. 20120328 ◽

Cited By ~ 29

Author(s):

Yinhua Wang ◽

Carolina Díaz Arenas ◽

Daniel M. Stoebel ◽

Tim F. Cooper

Keyword(s):

Escherichia Coli ◽

Genetic Background ◽

General Pattern ◽

Experimental Studies ◽

Natural Isolate ◽

Phenotypic Effect ◽

Fitness Effect ◽

Epistatic Interactions ◽

Beneficial Mutations ◽

E Coli

The phenotypic effect of mutations can depend on their genetic background, a phenomenon known as epistasis. Many experimental studies have found that epistasis is pervasive, and some indicate that it may follow a general pattern dependent on the fitness effect of the interacting mutations. These studies have, however, typically examined the effect of interactions between a small number of focal mutations in a single genetic background. Here, we extend this approach by considering how the interaction between two beneficial mutations that were isolated from a population of laboratory evolved Escherichia coli changes when they are added to divergent natural isolate strains of E. coli . We find that interactions between the focal mutations and the different genetic backgrounds are common. Moreover, the pair-wise interaction between the focal mutations also depended on their genetic background, being more negative in backgrounds with higher absolute fitness. Together, our results indicate the presence of interactions between focal mutations, but also caution that these interactions depend quantitatively on the wider genetic background.

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

10.1101/027086 ◽

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.

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