共查询到20条相似文献，搜索用时 0 毫秒
1.
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
2.
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
3.
Xiao‐Lin Chu Da‐Yong Zhang Angus Buckling Quan‐Guo Zhang 《Journal of evolutionary biology》2020,33(8):1020-1027
Temperature determines the rates of all biochemical and biophysical processes, and is also believed to be a key driver of macroevolutionary patterns. It is suggested that physiological constraints at low temperatures may diminish the fitness advantages of otherwise beneficial mutations; by contrast, relatively high, benign, temperatures allow beneficial mutations to efficiently show their phenotypic effects. To experimentally test this “mutational effects” mechanism, we examined the fitness effects of mutations across a temperature gradient using bacterial genotypes from the early stage of a mutation accumulation experiment with Escherichia coli. While the incidence of beneficial mutations did not significantly change across environmental temperatures, the number of mutations that conferred strong beneficial fitness effects was greater at higher temperatures. The results therefore support the hypothesis that warmer temperatures increase the chance and magnitude of positive selection, with implications for explaining the geographic patterns in evolutionary rates and understanding contemporary evolution under global warming. 相似文献
4.
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
5.
John W. Drake 《Critical reviews in biochemistry and molecular biology》2013,48(4):247-258
ABSTRACTIt has recently become clear that the classical notion of the random nature of mutation does not hold for the distribution of mutations among genes: most collections of mutants contain more isolates with two or more mutations than predicted by the mutant frequency on the assumption of a random distribution of mutations. Excesses of multiples are seen in a wide range of organisms, including riboviruses, DNA viruses, prokaryotes, yeasts, and higher eukaryotic cell lines and tissues. In addition, such excesses are produced by DNA polymerases in vitro. These “multiples” appear to be generated by transient, localized hypermutation rather than by heritable mutator mutations. The components of multiples are sometimes scattered at random and sometimes display an excess of smaller distances between mutations. As yet, almost nothing is known about the mechanisms that generate multiples, but such mutations have the capacity to accelerate those evolutionary pathways that require multiple mutations where the individual mutations are neutral or deleterious. Examples that impinge on human health may include carcinogenesis and the adaptation of microbial pathogens as they move between individual hosts. 相似文献
6.
Eugenio Lpez-Cortegano Rory J Craig Jobran Chebib Toby Samuels Andrew D Morgan Susanne A Kraemer Katharina B Bndel Rob W Ness Nick Colegrave Peter D Keightley 《Molecular biology and evolution》2021,38(9):3709
De novo mutations are central for evolution, since they provide the raw material for natural selection by regenerating genetic variation. However, studying de novo mutations is challenging and is generally restricted to model species, so we have a limited understanding of the evolution of the mutation rate and spectrum between closely related species. Here, we present a mutation accumulation (MA) experiment to study de novo mutation in the unicellular green alga Chlamydomonas incerta and perform comparative analyses with its closest known relative, Chlamydomonas reinhardtii. Using whole-genome sequencing data, we estimate that the median single nucleotide mutation (SNM) rate in C. incerta is μ = 7.6 × 10−10, and is highly variable between MA lines, ranging from μ = 0.35 × 10−10 to μ = 131.7 × 10−10. The SNM rate is strongly positively correlated with the mutation rate for insertions and deletions between lines (r > 0.97). We infer that the genomic factors associated with variation in the mutation rate are similar to those in C. reinhardtii, allowing for cross-prediction between species. Among these genomic factors, sequence context and complexity are more important than GC content. With the exception of a remarkably high C→T bias, the SNM spectrum differs markedly between the two Chlamydomonas species. Our results suggest that similar genomic and biological characteristics may result in a similar mutation rate in the two species, whereas the SNM spectrum has more freedom to diverge. 相似文献
7.
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
8.
Matthew T. Rutter Frank H. Shaw Charles B. Fenster 《Evolution; international journal of organic evolution》2010,64(6):1825-1835
Mutations are the ultimate source of genetic diversity and their contributions to evolutionary process depend critically on their rate and their effects on traits, notably fitness. Mutation rate and mutation effect can be measured simultaneously through the use of mutation accumulation lines, and previous mutation accumulation studies measuring these parameters have been performed in laboratory conditions. However, estimation of mutation parameters for fitness in wild populations requires assays in environments where mutations are exposed to natural selection and natural environmental variation. Here we quantify mutation parameters in both the wild and greenhouse environments using 100 25th generation Arabidopsis thaliana mutation accumulation lines. We found significantly greater mutational variance and a higher mutation rate for fitness under field conditions relative to greenhouse conditions. However, our field estimates were low when scaled to natural environmental variation. Many of the mutation accumulation lines have increased fitness, counter to the expectation that nearly all mutations decrease fitness. A high mutation rate and a low mutational contribution to phenotypic variation may explain observed levels of natural genetic variation. Our findings indicate that mutation parameters are not fixed, but are variables whose values may reflect the specific environment in which mutations are tested. 相似文献
9.
Knowledge of the rate and fitness effects of mutations is essential for understanding the process of evolution. Mutations are inherently difficult to study because they are rare and are frequently eliminated by natural selection. In the ciliate Tetrahymena thermophila, mutations can accumulate in the germline genome without being exposed to selection. We have conducted a mutation accumulation (MA) experiment in this species. Assuming that all mutations are deleterious and have the same effect, we estimate that the deleterious mutation rate per haploid germline genome per generation is U = 0.0047 (95% credible interval: 0.0015, 0.0125), and that germline mutations decrease fitness by s = 11% when expressed in a homozygous state (95% CI: 4.4%, 27%). We also estimate that deleterious mutations are partially recessive on average (h = 0.26; 95% CI: –0.022, 0.62) and that the rate of lethal mutations is <10% of the deleterious mutation rate. Comparisons between the observed evolutionary responses in the germline and somatic genomes and the results from individual-based simulations of MA suggest that the two genomes have similar mutational parameters. These are the first estimates of the deleterious mutation rate and fitness effects from the eukaryotic supergroup Chromalveolata and are within the range of those of other eukaryotes. 相似文献
10.
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
11.
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
12.
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
13.
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
14.
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
15.
Abstract We have analysed the effect of 288 generations of mutation accumulation (MA) on chromosome II competitive fitness in 21 full‐sib lines of Drosophila melanogaster and in a large control population, all derived from the same isogenic base. The rate of mean log‐fitness decline and that of increase of the between‐line variance were consistent with a low rate (λ ≈ 0.03 per gamete and generation), and moderate average fitness effect [E(s) ≈ 0.1] of deleterious mutation. Subsequently, crosses were made between pairs of MA lines, and these were maintained with effective size on the order of a few tens. In these crosses, MA recombinant chromosomes quickly recovered to about the average fitness level of control chromosomes. Thus, deleterious mutations responsible for the fitness decline were efficiently selected against in relatively small populations, confirming that their effects were larger than a few percent. 相似文献
16.
Spontaneous deleterious mutation has been measured in a handful of organisms, always under laboratory conditions and usually employing inbred species or genotypes. We report the results of a mutation accumulation experiment with an outbred annual plant, Raphanus raphanistrum, with lifetime fitness measured in both the field and the greenhouse. This is the first study to report the effects of spontaneous mutation measured under field conditions. Two large replicate populations (N(e) approximately 600) were maintained with random mating in the greenhouse under relaxed selection for nine generations before the field assay was performed and ten generations before the greenhouse assay. Each generation, every individual was mated twice, once as a pollen donor and once as a pollen recipient, and a single seed from each plant was chosen randomly to create the next generation. The ancestral population was maintained as seeds at 4 degrees C. Declines in lifetime fitness were observed in both the field (1.7% per generation; P= 0.27) and the greenhouse (0.6% per generation; P= 0.07). Significant increases in additive genetic variance for fitness were found for stems per day, flowers per stem, fruits per flower and seeds per fruit in the field as well as for fruits per flower in the greenhouse. Lack of significance of the fitness decline may be due to the short period of mutation accumulation, the use of outbred populations, or both. The percent declines in fitness are at the high end of the range observed in other mutation accumulation experiments and give some support to the idea that mutational effects may be magnified under harsher field conditions. Thus, measurement of mutational parameters under laboratory conditions may underestimate the effects of mutations in natural populations. 相似文献
17.
It has been hypothesized that new, spontaneous mutations tend to reduce fitness more severely in more stressful environments. To address this hypothesis, we grew plants representing 20 Arabidopsis thaliana mutation-accumulation (M-A) lines, advanced to generation 17, and their progenitor, in differing light conditions. The experiment was conducted in a greenhouse, and two treatments were used: full sun and shade, in which influx of red light was reduced relative to far-red. The shade treatment was considered the more stressful because mean absolute fitness was lower in that treatment, though not significantly so. Plants from generation 17 of M-A developed significantly faster than those from generation 0 in both treatments. A significant interaction between generation and treatment revealed that, counter to the hypothesis, M-A lines tended to have higher fitness on average relative to the progenitor in the shaded conditions, whereas, in full sun, the two generations were similar in fitness. A secondary objective of this experiment was to characterize the contribution of new mutations to genotype x environment interaction. We did not, however, detect a significant interaction between M-A line and treatment. Plots of the line-specific environmental responses indicate no tendency of new mutations to contribute to fitness trade-offs, between environments. They also do not support a model of conditionally deleterious mutation, in which a mutant reduces fitness only in a particular environment. These results suggest that interactions between genotype and light environment previously documented for A. thaliana are not explicable primarily as a consequence of steady input of spontaneous mutations having environment-specific effects. 相似文献
18.
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
19.
Abstract. We investigate maintenance of quantitative genetic variation at mutation-selection balance for multiple traits. The intrinsic strength of real stabilizing selection on one of these traits denoted the \"target trait\" and the observed strength of apparent stabilizing selection on the target trait can be quite different: the latter, which is estimable, is much smaller (i.e., implying stronger selection) than the former. Distinguishing them may enable the mutation load to be relaxed when considering multivariate stabilizing selection. It is shown that both correlations among mutational effects and among strengths of real stabilizing selection on the traits are not important unless they are high. The analysis for independent situations thus provides a good approximation to the case where mutant and stabilizing selection effects are correlated. Multivariate stabilizing selection can be regarded as a combination of stabilizing selection on the target trait and the pleiotropic direct selection on fitness that is solely due to the effects of real stabilizing selection on the hidden traits. As the overall fitness approaches a constant value as the number of traits increases, multivariate stabilizing selection can maintain abundant genetic variance only under quite weak selection. The common observations of high polygenic variance and strong stabilizing selection thus imply that if the mutation-selection balance is the true mechanism of maintenance of genetic variation, the apparent stabilizing selection cannot arise solely by real stabilizing selection simultaneously on many metric traits. 相似文献
20.
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