共查询到20条相似文献，搜索用时 0 毫秒
1.
Susanne A. Kraemer Katharina B. Böndel Robert W. Ness Peter D. Keightley Nick Colegrave 《Evolution; international journal of organic evolution》2017,71(12):2918-2929
Although all genetic variation ultimately stems from mutations, their properties are difficult to study directly. Here, we used multiple mutation accumulation (MA) lines derived from five genetic backgrounds of the green algae Chlamydomonas reinhardtii that have been previously subjected to whole genome sequencing to investigate the relationship between the number of spontaneous mutations and change in fitness from a nonevolved ancestor. MA lines were on average less fit than their ancestors and we detected a significantly negative correlation between the change in fitness and the total number of accumulated mutations in the genome. Likewise, the number of mutations located within coding regions significantly and negatively impacted MA line fitness. We used the fitness data to parameterize a maximum likelihood model to estimate discrete categories of mutational effects, and found that models containing one to two mutational effect categories (one neutral and one deleterious category) fitted the data best. However, the best‐fitting mutational effects models were highly dependent on the genetic background of the ancestral strain. 相似文献
2.
Analysis of a recent mutation accumulation (MA) experiment has led to the suggestion that as many as one-half of spontaneous mutations in Arabidopsis are advantageous for fitness. We evaluate this in the light of data from other MA experiments, along with molecular evidence, that suggest the vast majority of new mutations are deleterious. 相似文献
3.
Michael Lynch Jeff Blanchard David Houle Travis Kibota Stewart Schultz Larissa Vassilieva John Willis 《Evolution; international journal of organic evolution》1999,53(3):645-663
Mildly deleterious mutation has been invoked as a leading explanation for a diverse array of observations in evolutionary genetics and molecular evolution and is thought to be a significant risk of extinction for small populations. However, much of the empirical evidence for the deleterious-mutation process derives from studies of Drosophila melanogaster, some of which have been called into question. We review a broad array of data that collectively support the hypothesis that deleterious mutations arise in flies at rate of about one per individual per generation, with the average mutation decreasing fitness by about only 2% in the heterozygous state. Empirical evidence from microbes, plants, and several other animal species provide further support for the idea that most mutations have only mildly deleterious effects on fitness, and several other species appear to have genomic mutation rates that are of the order of magnitude observed in Drosophila. However, there is mounting evidence that some organisms have genomic deleterious mutation rates that are substantially lower than one per individual per generation. These lower rates may be at least partially reconciled with the Drosophila data by taking into consideration the number of germline cell divisions per generation. To fully resolve the existing controversy over the properties of spontaneous mutations, a number of issues need to be clarified. These include the form of the distribution of mutational effects and the extent to which this is modified by the environmental and genetic background and the contribution of basic biological features such as generation length and genome size to interspecific differences in the genomic mutation rate. Once such information is available, it should be possible to make a refined statement about the long-term impact of mutation on the genetic integrity of human populations subject to relaxed selection resulting from modern medical procedures. 相似文献
4.
Austin Burt Jacob G. Bundy Charles F. Baer 《Evolution; international journal of organic evolution》2016,70(10):2239-2246
A properly functioning organism must maintain metabolic homeostasis. Deleterious mutations degrade organismal function, presumably at least in part via effects on metabolic function. Here we present an initial investigation into the mutational structure of the Caenorhabditis elegans metabolome by means of a mutation accumulation experiment. We find that pool sizes of 29 metabolites vary greatly in their vulnerability to mutation, both in terms of the rate of accumulation of genetic variance (the mutational variance, VM) and the rate of change of the trait mean (the mutational bias, ΔM). Strikingly, some metabolites are much more vulnerable to mutation than any other trait previously studied in the same way. Although we cannot statistically assess the strength of mutational correlations between individual metabolites, principal component analysis provides strong evidence that some metabolite pools are genetically correlated, but also that there is substantial scope for independent evolution of different groups of metabolites. Averaged over mutation accumulation lines, PC3 is positively correlated with relative fitness, but a model in which metabolites are uncorrelated with fitness is nearly as good by Akaike's Information Criterion. 相似文献
5.
Andrew D. Morgan Rob W. Ness Peter D. Keightley Nick Colegrave 《Evolution; international journal of organic evolution》2014,68(9):2589-2602
Estimates of mutational parameters, such as the average fitness effect of a new mutation and the rate at which new genetic variation for fitness is created by mutation, are important for the understanding of many biological processes. However, the causes of interspecific variation in mutational parameters and the extent to which they vary within species remain largely unknown. We maintained multiple strains of the unicellular eukaryote Chlamydomonas reinhardtii, for approximately 1000 generations under relaxed selection by transferring a single cell every ～10 generations. Mean fitness of the lines tended to decline with generations of mutation accumulation whereas mutational variance increased. We did not find any evidence for differences among strains in any of the mutational parameters estimated. The overall change in mean fitness per cell division and rate of input of mutational variance per cell division were more similar to values observed in multicellular organisms than to those in other single‐celled microbes. However, after taking into account differences in genome size among species, estimates from multicellular organisms and microbes, including our new estimates from C. reinhardtii, become substantially more similar. Thus, we suggest that variation in genome size is an important determinant of interspecific variation in mutational parameters. 相似文献
6.
Veronique Etienne Erik C. Andersen José Miguel Ponciano Dustin Blanton Analucia Cadavid Joanna Joyner‐Matos Chikako Matsuba Brandon Tabman Charles F. Baer 《Evolution; international journal of organic evolution》2015,69(2):508-519
Understanding the genetic basis of susceptibility to pathogens is an important goal of medicine and of evolutionary biology. A key first step toward understanding the genetics and evolution of any phenotypic trait is characterizing the role of mutation. However, the rate at which mutation introduces genetic variance for pathogen susceptibility in any organism is essentially unknown. Here, we quantify the per‐generation input of genetic variance by mutation (VM) for susceptibility of Caenorhabditis elegans to the pathogenic bacterium Pseudomonas aeruginosa (defined as the median time of death, LT50). VM for LT50 is slightly less than VM for a variety of life‐history and morphological traits in this strain of C. elegans, but is well within the range of reported values in a variety of organisms. Mean LT50 did not change significantly over 250 generations of mutation accumulation. Comparison of VM to the standing genetic variance (VG) implies a strength of selection against new mutations of a few tenths of a percent. These results suggest that the substantial standing genetic variation for susceptibility of C. elegans to P. aeruginosa can be explained by polygenic mutation coupled with purifying selection. 相似文献
7.
Alethea D. Wang Nathaniel P. Sharp Aneil F. Agrawal 《Evolution; international journal of organic evolution》2014,68(3):840-853
Heterogeneity in the fitness effects of individual mutations has been found across different environmental and genetic contexts. Going beyond effects on individual mutations, how is the distribution of selective effects, f(s), altered by changes in genetic and environmental context? In this study, we examined changes in the major features of f(s) by estimating viability selection on 36 individual mutations in Drosophila melanogaster across two different environments in two different genetic backgrounds that were either adapted or nonadapted to the two test environments. Both environment and genetic background affected selection on individual mutations. However, the overall distribution f(s) appeared robust to changes in genetic background but both the mean, E(s), and the variance, V(s) were dependent on the environment. Between these two properties, V(s) was more sensitive to environmental change. Contrary to predictions of fitness landscape theory, the match between genetic background and assay environment (i.e., adaptedness) had little effect on f(s). 相似文献
8.
Abstract Deleterious mutation accumulation has been implicated in many biological phenomena and as a potentially significant threat to human health and the persistence of small populations. The vast majority of mutations with effects on fitness are known to be deleterious in a given environment, and their accumulation results in mean population fitness decline. However, whether populations are capable of recovering from negative effects of prolonged genetic bottlenecks via beneficial or compensatory mutation accumulation has not previously been tested. To address this question, long-term mutation-accumulation lines of the nematode Caenorhabditis elegans , previously propagated as single individuals each generation, were maintained in large population sizes under competitive conditions. Fitness assays of these lines and comparison to parallel mutation-accumulation lines and the ancestral control show that, while the process of fitness restoration was incomplete for some lines, full recovery of mean fitness was achieved in fewer than 80 generations. Several lines of evidence indicate that this fitness restoration was at least partially driven by compensatory mutation accumulation rather than a result of a generic form of laboratory adaptation. This surprising result has broad implications for the influence of the mutational process on many issues in evolutionary and conservation biology. 相似文献
9.
The pattern and extent of pleiotropic gene action can contribute substantially to the internal structure and shape of the additive genetic variance-covariance matrix (G)--a key determinant of evolutionary trajectories. We use data from our study (Estes et al. 2004) on the univariate effects of mutation in a mismatch-repair-defective strain, msh-2, of Caenorhabditis elegans to address the impact of increasing levels of selection on the magnitude and pattern of genetic covariance due to new mutations. Mutational covariances between three life-history traits are shown to exhibit a weak pattern of decline with increasing population size (increasing selection), while the orientation of mutational matrices remains reasonably constant. This suggests that mutations with smaller effects on fitness may tend to be slightly more confined in their influence than large-effect mutations (i.e., small-effect mutations reduce the magnitude of covariation between characters), but do not change the direction of this covariation. 相似文献
10.
Sandra Trindade Ana Sousa Isabel Gordo 《Evolution; international journal of organic evolution》2012,66(12):3815-3824
The role of mutations in evolution depends upon the distribution of their effects on fitness. This distribution is likely to depend on the environment. Indeed genotype‐by‐environment interactions are key for the process of local adaptation and ecological specialization. An important trait in bacterial evolution is antibiotic resistance, which presents a clear case of change in the direction of selection between environments with and without antibiotics. Here, we study the distribution of fitness effects of mutations, conferring antibiotic resistance to Escherichia coli, in benign and stressful environments without drugs. We interpret the distributions in the light of a fitness landscape model that assumes a single fitness peak. We find that mutation effects (s) are well described by a shifted gamma distribution, with a shift parameter that reflects the distance to the fitness peak and varies across environments. Consistent with the theoretical predictions of Fisher's geometrical model, with a Gaussian relationship between phenotype and fitness, we find that the main effect of stress is to increase the variance in s. Our findings are in agreement with the results of a recent meta‐analysis, which suggest that a simple fitness landscape model may capture the variation of mutation effects across species and environments. 相似文献
11.
Pepijn Luijckx Andrijana Stanić Aneil F. Agrawal 《Journal of evolutionary biology》2018,31(6):924-932
Theory predicts that fitness decline via mutation accumulation will depend on population size, but there are only a few direct tests of this key idea. To gain a qualitative understanding of the fitness effect of new mutations, we performed a mutation accumulation experiment with the facultative sexual rotifer Brachionus calyciflorus at six different population sizes under UV‐C radiation. Lifetime reproduction assays conducted after ten and sixteen UV‐C radiations showed that while small populations lost fitness, fitness losses diminished rapidly with increasing population size. Populations kept as low as 10 individuals were able to maintain fitness close to the nonmutagenized populations throughout the experiment indicating that selection was able to remove the majority of large effect mutations in small populations. Although our results also seem to imply that small populations are effectively immune to mutational decay, we caution against this interpretation. Given sufficient time, populations of moderate to large size can experience declines in fitness from accumulating weakly deleterious mutations as demonstrated by fitness estimates from simulations and, tentatively, from a long‐term experiment with populations of moderate size. There is mounting evidence to suggest that mutational distributions contain a heavier tail of large effects. Our results suggest that this is also true when the mutational spectrum is altered by UV radiation. 相似文献
12.
Populations of Chlamydomonas founded by single cells were cultured in chemostats for 50 days, representing about 125 generations. The mean and variance of division rate was measured daily by withdrawing cells from the effluent and culturing them for 24 h on filtered effluent medium solidified with agar. Mean fitness did not change during the period of culture, and the behavior of neutral markers indicated that no substitutions of novel beneficial mutations occurred. However, the variance of fitness increased markedly at about the same rate in two replicate populations. The standardized rate, or mutational heritability, was Vm/VE = 4-5 x 10(-3) per generation. This is substantially greater than most other estimates for characters closely correlated with fitness. Moreover, it seems difficult to reconcile with the absence of any change in mean fitness. We investigated the possibility that frequency-dependent selection was created by spatial heterogeneity within the culture vessel by testing cell populations with different phenotypes from the top, bottom, and surface of the chemostats. However, the differentiation of these populations seemed to be attributable to phenotypic plasticity, with no evidence that their characteristics were heritable. Finally, we report an experiment in which lines were selected for about 100 generations on solid or liquid medium. These lines became specifically adapted to the medium on which they were cultured, showing that liquid and solid media, even when chemically identical, provide different conditions of growth for Chlamydomonas. The genetic variance appearing in the cultures was therefore attributed to conditionally neutral mutations that were not expressed in the chemostat. This implies that rates of accumulation of mutational variance measured in the culture environment itself (where this can be done) may greatly underestimate the variation available for a response through selection to environmental change. Moreover, it suggests that chemostat populations may be more dynamic and more diverse than is usually thought. 相似文献
13.
Bengtsson BO 《Genetics》2012,191(4):1393-1395
Some genetic phenomena originate as mutations that are initially advantageous but decline in fitness until they become distinctly deleterious. Here I give the condition for a mutation-selection balance to form and describe some of the properties of the resulting equilibrium population. A characterization is also given of the fixation probabilities for such mutations. 相似文献
14.
As the ultimate source of genetic variation, spontaneous mutation is essential to evolutionary change. Theoretical studies over several decades have revealed the dependence of evolutionary consequences of mutation on specific mutational properties, including genomic mutation rates, U, and the effects of newly arising mutations on individual fitness, s. The recent resurgence of empirical effort to infer these properties for diverse organisms has not achieved consensus. Estimates, which have been obtained by methods that assume mutations are unidirectional in their effects on fitness, are imprecise. Both because a general approach must allow for occurrence of fitness-enhancing mutations, even if these are rare, and because recent evidence demands it, we present a new method for inferring mutational parameters. For the distribution of mutational effects, we retain Keightley's assumption of the gamma distribution, to take advantage of the flexibility of its shape. Because the conventional gamma is one sided, restricting it to unidirectional effects, we include an additional parameter, rho, as an amount it is displaced from zero. Estimation is accomplished by Markov chain Monte Carlo maximum likelihood. Through a limited set of simulations, we verify the accuracy of this approach. We apply it to analyze data on two reproductive fitness components from a 17-generation mutation-accumulation study of a Columbia accession of Arabidopsis thaliana in which 40 lines sampled in three generations were assayed simultaneously. For these traits, U approximately/= 0.1-0.2, with distributions of mutational effects broadly spanning zero, such that roughly half the mutations reduce reproductive fitness. One evolutionary consequence of these results is lower extinction risks of small populations of A. thaliana than expected from the process of mutational meltdown. A comprehensive view of the evolutionary consequences of mutation will depend on quantitatively accounting for fitness-enhancing, as well as fitness-reducing, mutations. 相似文献
15.
Pamela A Cote-Hammarlof Inês Fragata Julia Flynn David Mavor Konstantin B Zeldovich Claudia Bank Daniel N A Bolon 《Molecular biology and evolution》2021,38(2):368
The distribution of fitness effects (DFEs) of new mutations across different environments quantifies the potential for adaptation in a given environment and its cost in others. So far, results regarding the cost of adaptation across environments have been mixed, and most studies have sampled random mutations across different genes. Here, we quantify systematically how costs of adaptation vary along a large stretch of protein sequence by studying the distribution of fitness effects of the same ≈2,300 amino-acid changing mutations obtained from deep mutational scanning of 119 amino acids in the middle domain of the heat shock protein Hsp90 in five environments. This region is known to be important for client binding, stabilization of the Hsp90 dimer, stabilization of the N-terminal-Middle and Middle-C-terminal interdomains, and regulation of ATPase–chaperone activity. Interestingly, we find that fitness correlates well across diverse stressful environments, with the exception of one environment, diamide. Consistent with this result, we find little cost of adaptation; on average only one in seven beneficial mutations is deleterious in another environment. We identify a hotspot of beneficial mutations in a region of the protein that is located within an allosteric center. The identified protein regions that are enriched in beneficial, deleterious, and costly mutations coincide with residues that are involved in the stabilization of Hsp90 interdomains and stabilization of client-binding interfaces, or residues that are involved in ATPase–chaperone activity of Hsp90. Thus, our study yields information regarding the role and adaptive potential of a protein sequence that complements and extends known structural information. 相似文献
16.
Fitness effects of mutations may generally depend on temperature that influences all rate-limiting biophysical and biochemical processes. Earlier studies suggested that high temperatures may increase the availability of beneficial mutations (‘more beneficial mutations’), or allow beneficial mutations to show stronger fitness effects (‘stronger beneficial mutation effects’). The ‘more beneficial mutations’ scenario would inevitably be associated with increased proportion of conditionally beneficial mutations at higher temperatures. This in turn predicts that populations in warm environments show faster evolutionary adaptation but suffer fitness loss when faced with cold conditions, and those evolving in cold environments become thermal-niche generalists (‘hotter is narrower’). Under the ‘stronger beneficial mutation effects’ scenario, populations evolving in warm environments would show faster adaptation without fitness costs in cold environments, leading to a ‘hotter is (universally) better’ pattern in thermal niche adaptation. We tested predictions of the two competing hypotheses using an experimental evolution study in which populations of two model bacterial species, Escherichia coli and Pseudomonas fluorescens, evolved for 2400 generations at three experimental temperatures. Results of reciprocal transplant experiments with our P. fluorescens populations were largely consistent with the ‘hotter is narrower’ prediction. Results from the E. coli populations clearly suggested stronger beneficial mutation effects at higher assay temperatures, but failed to detect faster adaptation in populations evolving in warmer experimental environments (presumably because of limitation in the supply of genetic variation). Our results suggest that the influence of temperature on mutational effects may provide insight into the patterns of thermal niche adaptation and population diversification across thermal conditions. 相似文献
17.
Mutation rate may be condition dependent, whereby individuals in poor condition, perhaps from high mutation load, have higher mutation rates than individuals in good condition. Agrawal (J. Evol. Biol.15, 2002, 1004) explored the basic properties of fitness-dependent mutation rate (FDMR) in infinite populations and reported some heuristic results for finite populations. The key parameter governing how infinite populations evolve under FDMR is the curvature (k) of the relationship between fitness and mutation rate. We extend Agrawal's analysis to finite populations and consider dominance and epistasis. In finite populations, the probability of long-term existence depends on k. In sexual populations, positive curvature leads to low equilibrium mutation rate, whereas negative curvature results in high mutation rate. In asexual populations, negative curvature results in rapid extinction via 'mutational meltdown', whereas positive curvature sometimes allows persistence. We speculate that fitness-dependent mutation rate may provide the conditions for genetic architecture to diverge between sexual and asexual taxa. 相似文献
18.
Lindsay M. Johnson Olivia J. Smith Daniel A. Hahn Charles F. Baer 《Evolution; international journal of organic evolution》2020,74(11):2451-2464
Metabolic disorders have a large heritable component, and have increased markedly in human populations over the past few generations. Genome-wide association studies of metabolic traits typically find a substantial unexplained fraction of total heritability, suggesting an important role of spontaneous mutation. An alternative explanation is that epigenetic effects contribute significantly to the heritable variation. Here, we report a study designed to quantify the cumulative effects of spontaneous mutation on adenosine metabolism in the nematode Caenorhabditis elegans, including both the activity and concentration of two metabolic enzymes and the standing pools of their associated metabolites. The only prior studies on the effects of mutation on metabolic enzyme activity, in Drosophila melanogaster, found that total enzyme activity presents a mutational target similar to that of morphological and life-history traits. However, those studies were not designed to account for short-term heritable effects. We find that the short-term heritable variance for most traits is of similar magnitude as the variance among MA lines. This result suggests that the potential heritable effects of epigenetic variation in metabolic disease warrant additional scrutiny. 相似文献
19.
Aurora García-Dorado 《Evolution; international journal of organic evolution》1997,51(4):1130-1139
The empirical distribution of the mean viability of mutation accumulation lines, obtained from three published experiments, was analyzed using minimum-distance estimation. In two cases (Mukai et al. 1972; Ohnishi 1977), mutations were allowed to accumulate in copies of chromosome II protected from natural selection and recombination. In the other one (Fernández and López-Fanjul 1996), they accumulated in inbred lines derived from an isogenic stock. In contrast with currently accepted hypotheses, we consistently estimated low (about 0.01) genomic viability mutation rates, λ, and a small kurtosis of the distribution of mutational effects on viability (a) in the three datasets. Minimum-distance estimates of the per-generation mean viability change due to mutation (λE[a]) were also obtained. These were very similar for both chromosomal datasets, their absolute values being about five times smaller than estimates obtained from the observed change in mean viability during the mutation process. It must be noted that, in both experiments, viability was measured relative to the Cy chromosome of a Cy/Pm stock. Thus, an unnoticed viability increase in this Cy chromosome may have resulted in overestimation of the mean viability reduction in the lines. In parallel, minimum-distance estimation of λE(a) from inbred lines data (where the selective pressure during the accumulation process was larger) was even somewhat smaller, in absolute value, and very close to the estimate obtained by comparing the mean viability of the lines with that of the control isogenic line. The evolutionary importance of these results, as well as their relevance to the solution of the mutational load paradox, is discussed. 相似文献
20.
There has been a long‐standing conceptual debate over the legitimacy of assigning components of offspring fitness to parents for purposes of evolutionary analysis. The benefits and risks inherent in assigning fitness of offspring to parents have been given primarily as verbal arguments and no explicit theoretical analyses have examined quantitatively how the assignment of fitness can affect evolutionary inferences. Using a simple quantitative genetic model, we contrast the conclusions drawn about how selection acts on a maternal character when components of offspring fitness (such as early survival) are assigned to parents vs. when they are assigned directly to the individual offspring. We find that there are potential shortcomings of both possible assignments of fitness. In general, whenever there is a genetic correlation between the parental and direct effects on offspring fitness, assigning components of offspring fitness to parents yields incorrect dynamical equations and may even lead to incorrect conclusions about the direction of evolution. Assignment of offspring fitness to parents may also produce incorrect estimates of selection whenever environmental variation contributes to variance of the maternal trait. Whereas assignment of offspring fitness to the offspring avoids these potential problems, it introduces the possible problem of missing components of kin selection provided by the mother, which may not be detected in selection analyses. There are also certain conditions where either model can be appropriate because assignment of offspring fitness to parents may yield the same dynamical equations as assigning offspring fitness directly to offspring. We discuss these implications of the alternative assignments of fitness for modelling, selection analysis and experimentation in evolutionary biology. 相似文献