Fitness effects of mutations in bacteria

Mutation is the primary source of variation in any organism. Without it, natural selection cannot operate and organisms cannot adapt to novel environments. Mutation is also generally a source of defect: many mutations are not neutral but cause fitness decreases in the organisms where they arise. In bacteria, another important source of variation is horizontal gene transfer. This source of variation can also cause beneficial or deleterious effects. Determining the distribution of fitness effects of mutations in different environments and genetic backgrounds is an active research field. In bacteria, knowledge of these distributions is key for understanding important traits. For example, for determining the dynamics of microorganisms with a high genomic mutation rate (mutators), and for understanding the evolution of antibiotic resistance, and the emergence of pathogenic traits. All of these characteristics are extremely relevant for human health both at the individual and population levels. Experimental evolution has been a valuable tool to address these questions. Here, we review some of the important findings of mutation effects in bacteria revealed through laboratory experiments.     

Genetic variation and the fate of beneficial mutations in asexual populations

The fate of a newly arising beneficial mutation depends on many factors, such as the population size and the availability and fitness effects of other mutations that accumulate in the population. It has proved difficult to understand how these factors influence the trajectories of particular mutations, since experiments have primarily focused on characterizing successful clones emerging from a small number of evolving populations. Here, we present the results of a massively parallel experiment designed to measure the full spectrum of possible fates of new beneficial mutations in hundreds of experimental yeast populations, whether these mutations are ultimately successful or not. Using strains in which a particular class of beneficial mutation is detectable by fluorescence, we followed the trajectories of these beneficial mutations across 592 independent populations for 1000 generations. We find that the fitness advantage provided by individual mutations plays a surprisingly small role. Rather, underlying "background" genetic variation is quickly generated in our initially clonal populations and plays a crucial role in determining the fate of each individual beneficial mutation in the evolving population.     

The distribution of fitness effects among beneficial mutations

We know little about the distribution of fitness effects among new beneficial mutations, a problem that partly reflects the rarity of these changes. Surprisingly, though, population genetic theory allows us to predict what this distribution should look like under fairly general assumptions. Using extreme value theory, I derive this distribution and show that it has two unexpected properties. First, the distribution of beneficial fitness effects at a gene is exponential. Second, the distribution of beneficial effects at a gene has the same mean regardless of the fitness of the present wild-type allele. Adaptation from new mutations is thus characterized by a kind of invariance: natural selection chooses from the same spectrum of beneficial effects at a locus independent of the fitness rank of the present wild type. I show that these findings are reasonably robust to deviations from several assumptions. I further show that one can back calculate the mean size of new beneficial mutations from the observed mean size of fixed beneficial mutations.     

Spatial structure inhibits the rate of invasion of beneficial mutations in asexual populations

Populations in spatially structured environments may be divided into a number of (semi-) isolated subpopulations due to limited offspring dispersal. Limited dispersal and, as a consequence, local competition could slow down the invasion of fitter mutants, allowing the short-term coexistence of ancestral genotypes and mutants. We determined the rate of invasion of beneficial mutants of Escherichia coli, dispersed to different degrees in a spatially structured environment during 40 generations, experimentally and theoretically. Simulations as well as experimental data show a decrease in the rate of invasion with increasingly constrained dispersal. When a beneficial mutant invades from a single spot, competition with the ancestral genotype takes place only along the edges of the growing colony patch. As the colony grows, the fitness of the mutant will decrease due to a decrease in the mutant's fraction that effectively competes with the surrounding ancestor. Despite its inherently higher competitive ability, increased intragenotype competition prevents the beneficial mutant from rapidly taking over, causing short-term coexistence of superior and inferior genotypes.     

Estimation of the rate and effect of new beneficial mutations in asexual populations

The rate and effect of available beneficial mutations are key parameters in determining how a population adapts to a new environment. However, these parameters are poorly known, in large part because of the difficulty of designing and interpreting experiments to examine the rare and intrinsically stochastic process of mutation occurrence. We present a new approach to estimate the rate and selective advantage of beneficial mutations that underlie the adaptation of asexual populations. We base our approach on the analysis of experiments that track the effect of newly arising beneficial mutations on the dynamics of a neutral marker in evolving bacterial populations and develop efficient estimators of mutation rate and selective advantage. Using extensive simulations, we evaluate the accuracy of our estimators and conclude that they are quite robust to the use of relatively low experimental replication. To validate the predictions of our model, we compare theoretical and experimentally determined estimates of the selective advantage of the first beneficial mutation to fix in a series of ten replicate populations. We find that our theoretical predictions are not significantly different from experimentally determined selection coefficients. Application of our method to suitably designed experiments will allow estimation of how population evolvability depends on demographic and initial fitness parameters.     

Recombination speeds adaptation by reducing competition between beneficial mutations in populations of Escherichia coli

Identification of the selective forces contributing to the origin and maintenance of sex is a fundamental problem in biology. The Fisher–Muller model proposes that sex is advantageous because it allows beneficial mutations that arise in different lineages to recombine, thereby reducing clonal interference and speeding adaptation. I used the F plasmid to mediate recombination in the bacterium Escherichia coli and measured its effect on adaptation at high and low mutation rates. Recombination increased the rate of adaptation ~3-fold more in the high mutation rate treatment, where beneficial mutations had to compete for fixation. Sequencing of candidate loci revealed the presence of a beneficial mutation in six high mutation rate lines. In the absence of recombination, this mutation took longer to fix and, over the course of its substitution, conferred a reduced competitive advantage, indicating interference between competing beneficial mutations. Together, these results provide experimental support for the Fisher–Muller model and demonstrate that plasmid-mediated gene transfer can accelerate bacterial adaptation.     

Fitness effects of somatic mutations accumulating during vegetative growth

Evolutionary Ecology - The unique life form of plants promotes the accumulation of somatic mutations that can be passed to offspring in the next generation, because the same meristem cells...     

A method for detecting effect of beneficial mutations in natural populations of Drosophila melanogaster.

An experimental method is proposed for detecting the effects of positive natural selection on DNA polymorphisms. Since beneficial mutations are expected to increase in frequency faster than neutral mutations, variants which have reached high frequencies in a relatively short period could be linked to some beneficial mutation. D. melanogaster has a cosmopolitan polymorphic inversion -In(2L)t- whose age in some local populations has been estimated. Setting the age of In(2L)t as the upper limit for the age of variants, we searched for variants whose frequencies were possibly influenced by positive natural selection. We detected a single candidate whose frequency and distribution met the requirements imposed by our method.     

The distribution of fitness effects of new beneficial mutations in Pseudomonas fluorescens

Theoretical studies of adaptation emphasize the importance of understanding the distribution of fitness effects (DFE) of new mutations. We report the isolation of 100 adaptive mutants—without the biasing influence of natural selection—from an ancestral genotype whose fitness in the niche occupied by the derived type is extremely low. The fitness of each derived genotype was determined relative to a single reference type and the fitness effects found to conform to a normal distribution. When fitness was measured in a different environment, the rank order changed, but not the shape of the distribution. We argue that, even with detailed knowledge of the genetic architecture underpinning the adaptive types (as is the case here), the DFEs remain unpredictable, and we discuss the possibility that general explanations for the shape of the DFE might not be possible in the absence of organism-specific biological details.     

The distribution of beneficial and fixed mutation fitness effects close to an optimum

The distribution of the selection coefficients of beneficial mutations is pivotal to the study of the adaptive process, both at the organismal level (theories of adaptation) and at the gene level (molecular evolution). A now famous result of extreme value theory states that this distribution is an exponential, at least when considering a well-adapted wild type. However, this prediction could be inaccurate under selection for an optimum (because fitness effect distributions have a finite right tail in this case). In this article, we derive the distribution of beneficial mutation effects under a general model of stabilizing selection, with arbitrary selective and mutational covariance between a finite set of traits. We assume a well-adapted wild type, thus taking advantage of the robustness of tail behaviors, as in extreme value theory. We show that, under these general conditions, both beneficial mutation effects and fixed effects (mutations escaping drift loss) are beta distributed. In both cases, the parameters have explicit biological meaning and are empirically measurable; their variation through time can also be predicted. We retrieve the classic exponential distribution as a subcase of the beta when there are a moderate to large number of weakly correlated traits under selection. In this case too, we provide an explicit biological interpretation of the parameters of the distribution. We show by simulations that these conclusions are fairly robust to a lower adaptation of the wild type and discuss the relevance of our findings in the context of adaptation theories and experimental evolution.     

Unravelling the beneficial role of microbial contributors in reducing the allelopathic effects of weeds

The field of allelopathy is one of the most fascinating but controversial processes in plant ecology that offers an exciting, interdisciplinary, complex, and challenging study. In spite of the established role of soil microbes in plant health, their role has also been consolidated in studies of allelopathy. Moreover, allelopathy can be better understood by incorporating soil microbial ecology that determines the relevance of allelopathy phenomenon. Therefore, while discussing the role of allelochemicals in plant–plant interactions, the dynamic nature of soil microbes should not be overlooked. The occurrence and toxicity of allelochemicals in soil depend on various factors, but the type of microflora in the surroundings plays a crucial role because it can interfere with its allelopathic nature. Such microbes could be of prime importance for biological control management of weeds reducing the cost and ill effects of chemical herbicides. Among microbes, our main focus is on bacteria—as they are dominant among other microbes and are being used for enhancing crop production for decades—and fungi. Hence, to refer to both bacteria and fungi, we have used the term microbes. This review discusses the beneficial role of microbes in reducing the allelopathic effects of weeds. The review is mainly focused on various functions of bacteria in (1) reducing allelopathic inhibition caused by weeds to reduce crop yield loss, (2) building inherent defense capacity in plants against allelopathic weed, and (3) deciphering beneficial rhizospheric process such as chemotaxis/biofilm, degradation of toxic allelochemicals, and induced gene expression.     

The distribution of fitness effects among beneficial mutations in Fisher's geometric model of adaptation

Recent models of adaptation at the DNA sequence level assume that the fitness effects of new mutations show certain statistical properties. In particular, these models assume that the distribution of fitness effects among new mutations is in the domain of attraction of the so-called Gumbel-type extreme value distribution. This assumption has not, however, been justified on any biological or theoretical grounds. In this note, I study random mutation in one of the simplest models of mutation and adaptation-Fisher's geometric model. I show that random mutation in this model yields a distribution of mutational effects that belongs to the Gumbel type. I also show that the distribution of fitness effects among rare beneficial mutations in Fisher's model is asymptotically exponential. I confirm these analytic findings with exact computer simulations. These results provide some support for the use of Gumbel-type extreme value theory in studies of adaptation and point to a surprising connection between recent phenotypic- and sequence-based models of adaptation: in both, the distribution of fitness effects among rare beneficial mutations is approximately exponential.     

Species range expansion by beneficial mutations

A species' range can be limited when there is no genetic variation for a trait that allows for adaptation to more extreme environments. We study how range expansion occurs by the establishment of a new mutation that affects a quantitative trait in a spatially continuous population. The optimal phenotype for the trait varies linearly in space. The survival probabilities of new mutations affecting the trait are found by simulation. Shallow environmental gradients favour mutations that arise nearer to the range margin and that have smaller phenotypic effects than do steep gradients. Mutations that become established in shallow environmental gradients typically result in proportionally larger range expansions than those that establish in steep gradients. Mutations that become established in populations with high maximum growth rates tend to originate nearer to the range edge and to cause relatively smaller range expansion than mutations that establish in populations with low maximum growth rates. Under plausible parameter values, mutations that allow for range expansion tend to have large phenotypic effects (more than one phenotypic standard deviation) and cause substantial range expansions (15% or more). Sexual reproduction allows for larger range expansions and adaptation to more extreme environments than asexual reproduction.     

Evolution of cross-feeding in microbial populations

Although limited by a single resource, microbial populations that grow for long periods in continuous culture (chemostat) frequently evolve stable polymorphisms. These polymorphisms may be maintained by cross-feeding, where one strain partially degrades the primary energy resource and excretes an intermediate that is used as an energy resource by a second strain. It is unclear what selective advantage cross-feeding strains have over a single competitor that completely degrades the primary resource. Here we show that cross-feeding may evolve in microbial populations as a consequence of the following optimization principles: the rate of ATP production is maximized, the concentration of enzymes of the pathway is minimized, and the concentration of intermediates of the pathway is minimized.     

Long-term effects of timber harvesting on hemicellulolytic microbial populations in coniferous forest soils

Forest ecosystems need to be sustainably managed, as they are major reservoirs of biodiversity, provide important economic resources and modulate global climate. We have a poor knowledge of populations responsible for key biomass degradation processes in forest soils and the effects of forest harvesting on these populations. Here, we investigated the effects of three timber-harvesting methods, varying in the degree of organic matter removal, on putatively hemicellulolytic bacterial and fungal populations 10 or more years after harvesting and replanting. We used stable-isotope probing to identify populations that incorporated ¹³C from labeled hemicellulose, analyzing ¹³C-enriched phospholipid fatty acids, bacterial 16 S rRNA genes and fungal ITS regions. In soil microcosms, we identified 104 bacterial and 52 fungal hemicellulolytic operational taxonomic units (OTUs). Several of these OTUs are affiliated with taxa not previously reported to degrade hemicellulose, including the bacterial genera Methylibium, Pelomonas and Rhodoferax, and the fungal genera Cladosporium, Pseudeurotiaceae, Capronia, Xenopolyscytalum and Venturia. The effect of harvesting on hemicellulolytic populations was evaluated based on in situ bacterial and fungal OTUs. Harvesting treatments had significant but modest long-term effects on relative abundances of hemicellulolytic populations, which differed in strength between two ecozones and between soil layers. For soils incubated in microcosms, prior harvesting treatments did not affect the rate of incorporation of hemicellulose carbon into microbial biomass. In six ecozones across North America, distributions of the bacterial hemicellulolytic OTUs were similar, whereas distributions of fungal ones differed. Our work demonstrates that diverse taxa in soil are hemicellulolytic, many of which are differentially affected by the impact of harvesting on environmental conditions. However, the hemicellulolytic capacity of soil communities appears resilient.     

The fixation probability of two competing beneficial mutations

Suppose that a beneficial mutation is undergoing a selective sweep when another beneficial mutation arises at a linked locus. We study the fixation probability of the double mutant, i.e., one (produced by recombination) that carries both mutations. Previous analysis works well for the case where the earlier beneficial mutation confers a greater selective advantage than the later mutation, but not so well in the opposite case. We present an approach to approximating the fixation probability in the case where the later mutation confers a greater selective advantage.     

Fixation of beneficial mutations in the presence of epistatic interactions

We investigate the effect of deleterious mutations on the process of fixation of new advantageous mutants in an asexual population. In particular we wish to study the dependence of the process on the strength of the deleterious mutations. We suppose the existence of epistatic interaction between the genes. We study the model by means of branching process theory and also by numerical simulations. Our results show the occurrence of two distinct regimes of behavior for the probability of fixation of these variants. The occurrence of either regime depends on the ratio between the selective advantage of the beneficial mutation s _b and on the selective parameter for deleterious mutations s _b . In the former, which takes place for s _b /s _d ≲ 1, the probability of fixation increases with the epistasis parameter α, whereas for s _b /s _d ≫ 1 the probability of fixation is a complex function of α and the mutation rate U. Surprisingly, we find that for the multiplicative landscape (α = 1) the probability of fixation P _fix is given by where π (s _b ) is the probability of fixation for the two-allele model in the absence of mutations as calculated by Haldane (1927, Proc. Camb. Phil. Soc., 26, 220–230) and Kimura (1962, Genetics, 47, 713–719).     

Fitness effects of derived deleterious mutations in four closely related wild tomato species with spatial structure

A key issue in evolutionary biology is an improved understanding of the genetic mechanisms by which species adapt to various environments. Using DNA sequence data, it is possible to quantify the number of adaptive and deleterious mutations, and the distribution of fitness effects of new mutations (its mean and variance) by simultaneously taking into account the demography of a given species. We investigated how selection functions at eight housekeeping genes of four closely related, outcrossing species of wild tomatoes that are native to diverse environments in western South America (Solanum arcanum, S. chilense, S. habrochaites and S. peruvianum). We found little evidence for adaptive mutations but pervasive evidence for strong purifying selection in coding regions of the four species. In contrast, the strength of purifying selection seems to vary among the four species in non-coding (NC) regions (introns). Using F(ST)-based measures of fixation in subdivided populations, we suggest that weak purifying selection has affected the NC regions of S. habrochaites, S. chilense and S. peruvianum. In contrast, NC regions in S. arcanum show a distribution of fitness effects with mutations being either nearly neutral or very strongly deleterious. These results suggest that closely related species with similar genetic backgrounds but experiencing contrasting environments differ in the variance of deleterious fitness effects.