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 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 Characterization of the Two Mycobacterium tuberculosis recA Promoters

2003 ◽  
Vol 185 (20) ◽  
pp. 6005-6015 ◽  
Author(s):  
Krishna K. Gopaul ◽  
Patricia C. Brooks ◽  
Jean-François Prost ◽  
Elaine O. Davis
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Mycobacterium Tuberculosis ◽  
Promoter Activity ◽  
The Other ◽  
Expression Level ◽  
Promoter Elements ◽  
Kinetics Of

ABSTRACT The recA gene of Mycobacterium tuberculosis is unusual in that it is expressed from two promoters, one of which, P1, is DNA damage inducible independently of LexA and RecA, while the other, P2, is regulated by LexA in the classical way (E. O. Davis, B. Springer, K. K. Gopaul, K. G. Papavinasasundaram, P. Sander, and E. C. Böttger, Mol. Microbiol. 46:791-800, 2002). In this study we characterized these two promoters in more detail. Firstly, we localized the promoter elements for each of the promoters, and in so doing we identified a mutation in each promoter which eliminates promoter activity. Interestingly, a motif with similarity to Escherichia coli σ70 −35 elements but located much closer to the −10 element is important for optimal expression of P1, whereas the sequence at the −35 location is not. Secondly, we found that the sequences flanking the promoters can have a profound effect on the expression level directed by each of the promoters. Finally, we examined the contribution of each of the promoters to recA expression and compared their kinetics of induction following DNA damage.

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

2010 ◽  
Vol 192 (17) ◽  
pp. 4517-4521 ◽  
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.

scholarly journals Phenotypic Tolerance: Antibiotic Enrichment of Noninherited Resistance in Bacterial Populations

2005 ◽  
Vol 49 (4) ◽  
pp. 1483-1494 ◽  
Author(s):  
C. Wiuff ◽  
R. M. Zappala ◽  
R. R. Regoes ◽  
K. N. Garner ◽  
F. Baquero ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mathematical Model ◽  
Mathematical Models ◽  
Antibiotic Treatment ◽  
A Priori ◽  
The Other ◽  
Bacterial Populations ◽  
Microbiological Outcome

ABSTRACT When growing bacteria are exposed to bactericidal concentrations of antibiotics, the sensitivity of the bacteria to the antibiotic commonly decreases with time, and substantial fractions of the bacteria survive. Using Escherichia coli CAB1 and antibiotics of five different classes (ampicillin, ciprofloxacin, rifampin, streptomycin, and tetracycline), we examine the details of this phenomenon and, with the aid of mathematical models, develop and explore the properties and predictions of three hypotheses that can account for this phenomenon: (i) antibiotic decay, (ii) inherited resistance, and (iii) phenotypic tolerance. Our experiments cause us to reject the first two hypotheses and provide evidence that this phenomenon can be accounted for by the antibiotic-mediated enrichment of subpopulations physiologically tolerant to but genetically susceptible to these antibiotics, phenotypic tolerance. We demonstrate that tolerant subpopulations generated by exposure to one concentration of an antibiotic are also tolerant to higher concentrations of the same antibiotic and can be tolerant to antibiotics of the other four types. Using a mathematical model, we explore the effects of phenotypic tolerance to the microbiological outcome of antibiotic treatment and demonstrate, a priori, that it can have a profound effect on the rate of clearance of the bacteria and under some conditions can prevent clearance that would be achieved in the absence of tolerance.

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 Genetic background affects epistatic interactions between two beneficial mutations

2013 ◽  
Vol 9 (1) ◽  
pp. 20120328 ◽  
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.

scholarly journals The Evolution of Mutator Genes in Bacterial Populations: The Roles of Environmental Change and Timing

Genetics ◽  
2003 ◽  
Vol 164 (3) ◽  
pp. 843-854 ◽  
Author(s):  
Mark M Tanaka ◽  
Carl T Bergstrom ◽  
Bruce R Levin
Keyword(s):  
Selective Sweeps ◽  
Deleterious Mutations ◽  
Beneficial Mutation ◽  
Beneficial Mutations ◽  
Bacterial Populations ◽  
High Frequencies ◽  
Laboratory Populations ◽  
Experimental And Theoretical Studies ◽  
Theoretical Results ◽  
Mutator Genes

Abstract Recent studies have found high frequencies of bacteria with increased genomic rates of mutation in both clinical and laboratory populations. These observations may seem surprising in light of earlier experimental and theoretical studies. Mutator genes (genes that elevate the genomic mutation rate) are likely to induce deleterious mutations and thus suffer an indirect selective disadvantage; at the same time, bacteria carrying them can increase in frequency only by generating beneficial mutations at other loci. When clones carrying mutator genes are rare, however, these beneficial mutations are far more likely to arise in members of the much larger nonmutator population. How then can mutators become prevalent? To address this question, we develop a model of the population dynamics of bacteria confronted with ever-changing environments. Using analytical and simulation procedures, we explore the process by which initially rare mutator alleles can rise in frequency. We demonstrate that subsequent to a shift in environmental conditions, there will be relatively long periods of time during which the mutator subpopulation can produce a beneficial mutation before the ancestral subpopulations are eliminated. If the beneficial mutation arises early enough, the overall frequency of mutators will climb to a point higher than when the process began. The probability of producing a subsequent beneficial mutation will then also increase. In this manner, mutators can increase in frequency over successive selective sweeps. We discuss the implications and predictions of these theoretical results in relation to antibiotic resistance and the evolution of mutation rates.

scholarly journals Molecular mechanisms involved in the regulation of mutation rates in bacteria

2017 ◽  
Vol 118 (4) ◽  
Author(s):  
Ivan Matic
Keyword(s):  
Mutation Rate ◽  
Molecular Mechanisms ◽  
Point Of View ◽  
Mutation Rates ◽  
Beneficial Mutations ◽  
Bacterial Populations ◽  
Multiple Strategies ◽  
Induced Mutagenesis ◽  
The Cost ◽  
Evolutionary Point

Organisms live in constantly changing environments in which, the nature, severity and frequency of the environmental stresses are very variable. Organisms possess multiple strategies for coping with the environmental fluctuations. One such strategy is modulation of mutation rates as a function of the degree of adaptation to the environment. When adaptation is limited by the available genetic variability, natural selection favors cells having high mutation rates in bacterial populations. High mutation rates can be advantageous because they increase the probability of generation of beneficial mutations. Constitutive mutator alleles are carried to high frequency through hitchhiking with beneficial mutations they generate. However, once the adaptation is achieved, the cost of deleterious mutations generated by constitutive mutator alleles reduces cellular fitness. For this reason, the possibility of adapting the mutation rate to environmental conditions is interesting from an evolutionary point of view. Stress-induced mutagenesis allows rapid adaptation to complex environmental challenges without compromising the population fitness because it reduces the overall cost of a high mutation rate. Here we review the molecular mechanisms involved in the control of modulation of mutation rates in bacteria.

Infection of Escherichia coli with bacteriophages

1969 ◽  
Vol 27 ◽  
pp. 370-371
Author(s):  
Manfred E. Bayer
Keyword(s):  
Escherichia Coli ◽  
Nucleic Acid ◽  
Cell Surface ◽  
Virus Type ◽  
Infection Process ◽  
Adsorption Site ◽  
The Other ◽  
Specific Receptors ◽  
Bacterial Receptors

The first step in the infection of a bacterium by a virus consists of a collision between cell and bacteriophage. The presence of virus-specific receptors on the cell surface will trigger a number of events leading eventually to release of the phage nucleic acid. The execution of the various "steps" in the infection process varies from one virus-type to the other, depending on the anatomy of the virus. Small viruses like ØX 174 and MS2 adsorb directly with their capsid to the bacterial receptors, while other phages possess attachment organelles of varying complexity. In bacteriophages T3 (Fig. 1) and T7 the small conical processes of their heads point toward the adsorption site; a welldefined baseplate is attached to the head of P22; heads without baseplates are not infective.

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