scholarly journals Dissection of the mutation accumulation process during bacterial range expansions

2020 ◽  
Author(s):  
Lars Bosshard ◽  
Stephan Peischl ◽  
Martin Ackermann ◽  
Laurent Excoffier

Abstract Background Recent experimental work has shown that the evolutionary dynamics of bacteria expanding across space can differ dramatically from what we expect under well-mixed conditions. During spatial expansion, deleterious mutations can accumulate due to inefficient selection on the expansion front, potentially interfering with and modifying adaptive evolutionary processes.Results We used whole genome sequencing to follow the genomic evolution of 10 mutator Escherichia coli lines during 39 days (∼1650 generations) of a spatial expansion, which allowed us to gain a temporal perspective on the interaction of adaptive and non-adaptive evolutionary processes during range expansions. We used elastic net regression to infer the positive or negative effects of mutations on colony growth. Even though the colony size, measured after three day of growth, decreased at the end of the experiment in all 10 lines, and mutations accumulated at a nearly constant rate over the whole experiment. We find evidence that beneficial mutations accumulate primarily at an early stage of the experiment, leading to a non-linear change of colony size over time. Indeed, colony size remains almost constant at the beginning of the experiment and then decreases after ∼12 days of evolution. We also find that beneficial mutations are enriched in flagella genes, genes encoding transport proteins, and genes coding for the membrane structure, whereas deleterious mutations show no enrichment for any biological process.Conclusions Our experiment shows that beneficial mutations target specific biological functions mostly involved in inter or extra membrane processes, whereas deleterious mutations are randomly distributed over the whole gnome. It thus appears that the interaction between genetic drift and the availability or depletion of beneficial mutations determines the change in fitness of bacterial populations during range expansion.

2020 ◽  
Author(s):  
Lars Bosshard ◽  
Stephan Peischl ◽  
Martin Ackermann ◽  
Laurent Excoffier

Abstract Background Recent experimental work has shown that the evolutionary dynamics of bacteria expanding across space can differ dramatically from what we expect under well-mixed conditions. During spatial expansion, deleterious mutations can accumulate due to inefficient selection on the expansion front, potentially interfering with and modifying adaptive evolutionary processes. Results We used whole genome sequencing to follow the genomic evolution of 10 mutator Escherichia coli lines during 39 days (∼1650 generations) of a spatial expansion, which allowed us to gain a temporal perspective on the interaction of adaptive and non-adaptive evolutionary processes during range expansions. We used elastic net regression to infer the positive or negative effects of mutations on colony growth. The colony size, measured after three day of growth, decreased at the end of the experiment in all 10 lines, and mutations accumulated at a nearly constant rate over the whole experiment. We find evidence that beneficial mutations accumulate primarily at an early stage of the experiment, leading to a non-linear change of colony size over time. Indeed, the rate of colony size expansion remains almost constant at the beginning of the experiment and then decreases after ∼12 days of evolution. We also find that beneficial mutations are enriched in genes encoding transport proteins, and genes coding for the membrane structure, whereas deleterious mutations show no enrichment for any biological process. Conclusions Our experiment shows that beneficial mutations target specific biological functions mostly involved in inter or extra membrane processes, whereas deleterious mutations are randomly distributed over the whole genome. It thus appears that the interaction between genetic drift and the availability or depletion of beneficial mutations determines the change in fitness of bacterial populations during range expansion.


2020 ◽  
Author(s):  
Lars Bosshard ◽  
Stephan Peischl ◽  
Martin Ackermann ◽  
Laurent Excoffier

Abstract Background Recent experimental work has shown that the evolutionary dynamics of bacteria expanding across space can differ dramatically from what we expect under well-mixed conditions. During spatial expansion, deleterious mutations can accumulate due to inefficient selection on the expansion front, potentially interfering with and modifying adaptive evolutionary processes. Results We used whole genome sequencing to follow the genomic evolution of 10 mutator Escherichia coli lines during 39 days ( ~1650 generations) of a spatial expansion, which allowed us to gain a temporal perspective on the interaction of adaptive and non-adaptive evolutionary processes during range expansions. We used elastic net regression to infer the positive or negative effects of mutations on colony growth. The colony size, measured after three day of growth, decreased at the end of the experiment in all 10 lines, and mutations accumulated at a nearly constant rate over the whole experiment. We find evidence that beneficial mutations accumulate primarily at an early stage of the experiment, leading to a non-linear change of colony size over time. Indeed, the rate of colony size expansion remains almost constant at the beginning of the experiment and then decreases after ~12 days of evolution. We also find that beneficial mutations are enriched in genes encoding transport proteins, and genes coding for the membrane structure, whereas deleterious mutations show no enrichment for any biological process. Conclusions Our experiment shows that beneficial mutations target specific biological functions mostly involved in inter or extra membrane processes, whereas deleterious mutations are randomly distributed over the whole genome. It thus appears that the interaction between genetic drift and the availability or depletion of beneficial mutations determines the change in fitness of bacterial populations during range expansion.


Genetics ◽  
2003 ◽  
Vol 164 (3) ◽  
pp. 843-854 ◽  
Author(s):  
Mark M Tanaka ◽  
Carl T Bergstrom ◽  
Bruce R Levin

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.


2019 ◽  
Vol 36 (10) ◽  
pp. 2313-2327 ◽  
Author(s):  
Lars Bosshard ◽  
Stephan Peischl ◽  
Martin Ackermann ◽  
Laurent Excoffier

AbstractBacterial populations have been shown to accumulate deleterious mutations during spatial expansions that overall decrease their fitness and ability to grow. However, it is unclear if and how they can respond to selection in face of this mutation load. We examine here if artificial selection can counteract the negative effects of range expansions. We examined the molecular evolution of 20 mutator lines selected for fast expansions (SEL) and compared them to 20 other mutator lines freely expanding without artificial selection (CONTROL). We find that the colony size of all 20 SEL lines have increased relative to the ancestral lines, unlike CONTROL lines, showing that enough beneficial mutations are produced during spatial expansions to counteract the negative effect of expansion load. Importantly, SEL and CONTROL lines have similar numbers of mutations indicating that they evolved for the same number of generations and that increased fitness is not due to a purging of deleterious mutations. We find that loss of function mutations better explain the increased colony size of SEL lines than nonsynonymous mutations or a combination of the two. Interestingly, most loss of function mutations are found in simple sequence repeats (SSRs) located in genes involved in gene regulation and gene expression. We postulate that such potentially reversible mutations could play a major role in the rapid adaptation of bacteria to changing environmental conditions by shutting down expensive genes and adjusting gene expression.


2013 ◽  
Vol 9 (1) ◽  
pp. 20120961 ◽  
Author(s):  
Ram P. Maharjan ◽  
Bin Liu ◽  
Yang Li ◽  
Peter R. Reeves ◽  
Lei Wang ◽  
...  

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.


Genetics ◽  
1998 ◽  
Vol 149 (4) ◽  
pp. 2089-2097 ◽  
Author(s):  
Jody Hey

Abstract If multiple linked polymorphisms are under natural selection, then conflicts arise and the efficiency of natural selection is hindered relative to the case of no linkage. This simple interaction between linkage and natural selection creates an opportunity for mutations that raise the level of recombination to increase in frequency and have an enhanced chance of fixation. This important finding by S. Otto and N. Barton means that mutations that raise the recombination rate, but are otherwise neutral, will be selectively favored under fairly general circumstances of multilocus selection and linkage. The effect described by Otto and Barton, which was limited to neutral modifiers, can also be extended to include all modifiers of recombination, both beneficial and deleterious. Computer simulations show that beneficial mutations that also increase recombination have an increased chance of fixation. Similarly, deleterious mutations that also decrease recombination have an increased chance of fixation. The results suggest that a simple model of recombination modifiers, including both neutral and pleiotropic modifiers, is a necessary explanation for the evolutionary origin of recombination.


Genetics ◽  
2003 ◽  
Vol 164 (3) ◽  
pp. 1099-1118 ◽  
Author(s):  
Sarah P Otto

AbstractIn diploids, sexual reproduction promotes both the segregation of alleles at the same locus and the recombination of alleles at different loci. This article is the first to investigate the possibility that sex might have evolved and been maintained to promote segregation, using a model that incorporates both a general selection regime and modifier alleles that alter an individual’s allocation to sexual vs. asexual reproduction. The fate of different modifier alleles was found to depend strongly on the strength of selection at fitness loci and on the presence of inbreeding among individuals undergoing sexual reproduction. When selection is weak and mating occurs randomly among sexually produced gametes, reductions in the occurrence of sex are favored, but the genome-wide strength of selection is extremely small. In contrast, when selection is weak and some inbreeding occurs among gametes, increased allocation to sexual reproduction is expected as long as deleterious mutations are partially recessive and/or beneficial mutations are partially dominant. Under strong selection, the conditions under which increased allocation to sex evolves are reversed. Because deleterious mutations are typically considered to be partially recessive and weakly selected and because most populations exhibit some degree of inbreeding, this model predicts that higher frequencies of sex would evolve and be maintained as a consequence of the effects of segregation. Even with low levels of inbreeding, selection is stronger on a modifier that promotes segregation than on a modifier that promotes recombination, suggesting that the benefits of segregation are more likely than the benefits of recombination to have driven the evolution of sexual reproduction in diploids.


2013 ◽  
Vol 128 (2) ◽  
pp. 379-387 ◽  
Author(s):  
Maiken Ueland ◽  
Heloise A. Breton ◽  
Shari L. Forbes

Blood ◽  
1990 ◽  
Vol 75 (12) ◽  
pp. 2286-2291 ◽  
Author(s):  
K Koike ◽  
T Nakahata ◽  
T Kubo ◽  
T Kikuchi ◽  
M Takagi ◽  
...  

We investigated the effect of interleukin-6 (IL-6) on murine megakaryocytopoiesis in a serum-free culture system. The addition of IL- 6 to a culture containing interleukin-3 (IL-3) resulted in a significant increase in the number of megakaryocyte colonies by bone marrow cells of normal mice. The megakaryocytic progenitors that survive exposure to 5-fluorouracil (5-FU) exhibited a more significant response to IL-6 and IL-3. Polyclonal anti-IL-6 antibody neutralized the stimulatory effect of IL-6 on megakaryocyte colony growth supported by IL-3. Delayed addition experiments and replating experiments of blast cell colonies showed that megakaryocytic progenitors are supported by IL-3 in the early stage of the development but require IL- 6 for their subsequent proliferation and differentiation. In addition, IL-6 increased the size of megakaryocytes in granulocyte-macrophage- megakaryocyte colonies. The combination of granulocyte colony- stimulating factor or granulocyte-macrophage colony stimulating factor with IL-3 resulted in an increase in the granulocyte-macrophage colony growth of bone marrow cells of 5-FU-treated mice or normal mice, respectively, but had little effect on the enhancement of pure and mixed megakaryocyte colony growth. These results suggest that IL-6 plays an important role in murine megakaryocytopoiesis.


2016 ◽  
Author(s):  
Paula Tataru ◽  
Maéva Mollion ◽  
Sylvain Glemin ◽  
Thomas Bataillon

ABSTRACTThe distribution of fitness effects (DFE) encompasses deleterious, neutral and beneficial mutations. It conditions the evolutionary trajectory of populations, as well as the rate of adaptive molecular evolution (α). Inference of DFE and α from patterns of polymorphism (SFS) and divergence data has been a longstanding goal of evolutionary genetics. A widespread assumption shared by numerous methods developed so far to infer DFE and α from such data is that beneficial mutations contribute only negligibly to the polymorphism data. Hence, a DFE comprising only deleterious mutations tends to be estimated from SFS data, and α is only predicted by contrasting the SFS with divergence data from an outgroup. Here, we develop a hierarchical probabilistic framework that extends on previous methods and also can infer DFE and α from polymorphism data alone. We use extensive simulations to examine the performance of our method. We show that both a full DFE, comprising both deleterious and beneficial mutations, and α can be inferred without resorting to divergence data. We demonstrate that inference of DFE from polymorphism data alone can in fact provide more reliable estimates, as it does not rely on strong assumptions about a shared DFE between the outgroup and ingroup species used to obtain the SFS and divergence data. We also show that not accounting for the contribution of beneficial mutations to polymorphism data leads to substantially biased estimates of the DFE and α. We illustrate these points using our newly developed framework, while also comparing to one of the most widely used inference methods available.


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