首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
Previous studies with diploid yeast have shown that the deletion of one allele at a single locus typically has little impact on fitness under conditions promoting fast growth. Here, we confirm and quantify this finding. The strong dominance of functional over nonfunctional alleles is predicted by the metabolic control theory which assumes that the cell is a system of metabolic fluxes and that the total metabolic rate is equivalent to fitness. To test whether these requirements are critical, we tested dominance under conditions of long‐term starvation when metabolism is low and thus the metabolic activities of proteins are likely inadequate or imbalanced. More fundamentally, the central assumption of the model, that high metabolic rate translates into high fitness, appears implausible. Contrary to these conjectures, we found that the mean rate of survival of starving heterozygotes was affected only slightly more than was the mean rate of growth under good conditions. Under none of the two treatments the central prediction of the model, that fitness of heterozygous strains is higher for the enzymatic proteins than for nonenzymatic ones, was confirmed. Our data add to growing uncertainty whether the metabolic control theory is sufficient to explain the remarkable ubiquity of strong genetic dominance.  相似文献   

2.
Rate of protein evolution versus fitness effect of gene deletion   总被引:6,自引:0,他引:6  
Whether nonessential genes evolve faster than essential genes has been a controversial issue. To resolve this issue, we use the data from a nearly complete set of single-gene deletions in the yeast Saccharomyces cerevisiae to assess protein dispensability. Also, instead of the nematode, which was used previously but is only distantly related to S. cerevisiae, we use another yeast, Candida albicans, as a second species to estimate the evolutionary distances between orthologous genes in two species. Our analysis reveals only a weak correlation between protein dispensability and evolutionary rate. More important, the correlation disappears when duplicate genes are removed from the analysis. And surprisingly, the average rate of nonsynonymous substitution is considerably lower than that for single-copy genes in the yeast genome. This observation suggests that structural constraints are more important in determining the rate of evolution of a protein than dispensability because duplicate genes are on average more dispensable than single-copy genes. For duplicate genes, those with only a weak effect or no effect of deletion on fitness evolve on average faster than those with a moderate or strong effect of deletion on fitness, which in turn evolve on average faster than those with a lethal effect of deletion.  相似文献   

3.
We estimated the average dominance coefficient of mildly deleterious mutations (h, the proportion by which mutations in the heterozygous state reduce fitness components relative to those in the homozygous state) in the nematode Caenorhabditis elegans. From 56 worm lines that carry mutations induced by the point mutagen ethyl methanesulfonate (EMS), we selected 19 lines that are relatively high in fitness and estimated the viabilities, productivities, and relative fitnesses of heterozygotes and homozygotes compared to the ancestral wild type. There was very little effect of homozygous or heterozygous mutations on egg-to-adult viability. For productivity and relative fitness, we found that the average dominance coefficient, h, was approximately 0.1, suggesting that mildly deleterious mutations are on average partially recessive. These estimates were not significantly different from zero (complete recessivity) but were significantly different from 0.5 (additivity). In addition, there was a significant amount of variation in h among lines, and analysis of average dominance coefficients of individual lines suggested that several lines showed overdominance for fitness. Further investigation of two of these lines partially confirmed this finding.  相似文献   

4.
The boom of massive parallel sequencing (MPS) technology and its applications in conservation of natural and managed populations brings new opportunities and challenges to meet the scientific questions that can be addressed. Genomic conservation offers a wide range of approaches and analytical techniques, with their respective strengths and weaknesses that rely on several implicit assumptions. However, finding the most suitable approaches and analysis regarding our scientific question are often difficult and time‐consuming. To address this gap, a recent workshop entitled ‘ConGen 2015’ was held at Montana University in order to bring together the knowledge accumulated in this field and to provide training in conceptual and practical aspects of data analysis applied to the field of conservation and evolutionary genomics. Here, we summarize the expertise yield by each instructor that has led us to consider the importance of keeping in mind the scientific question from sampling to management practices along with the selection of appropriate genomics tools and bioinformatics challenges.  相似文献   

5.
The extent to which heterozygosity-fitness correlations (HFCs) are expected in wild populations is an important and unresolved question in evolutionary biology, because it relates to our understanding of the genetic architecture of fitness. Here, we report a study of HFCs in a wild, noninbred population of great tits (Parus major), based on a sample comprising 281 individuals typed at 26 markers, resulting in a data set comprising over 5600 genotypes. We regressed pedigree-derived f-score and multilocus genetic diversity against eight life-history traits known to be associated with fitness in this population, including lifetime reproductive success (LRS), as well as several morphological traits under weak selection. We found no evidence for either multilocus or single-locus HFCs for any morphological or fitness trait, and further found no evidence that effect sizes were stronger for those life-history traits more closely associated with reproductive fitness. This result may, in part, be explained by the fact that we found no evidence that our set of 26 markers had any power to infer genome-wide heterozygosity in this population and that marker-derived heterozygosity was uncorrelated with pedigree-derived f-score. Overall, these results emphasize the fact that the often-reported strong HFCs detected in small, inbred populations do not reflect a general phenomenon of increasing individual reproductive fitness with increasing heterozygosity.  相似文献   

6.
Mechanisms of haploinsufficiency revealed by genome-wide profiling in yeast   总被引:16,自引:0,他引:16  
Haploinsufficiency is defined as a dominant phenotype in diploid organisms that are heterozygous for a loss-of-function allele. Despite its relevance to human disease, neither the extent of haploinsufficiency nor its precise molecular mechanisms are well understood. We used the complete set of Saccharomyces cerevisiae heterozygous deletion strains to survey the genome for haploinsufficiency via fitness profiling in rich (YPD) and minimal media to identify all genes that confer a haploinsufficient growth defect. This assay revealed that approximately 3% of all approximately 5900 genes tested are haploinsufficient for growth in YPD. This class of genes is functionally enriched for metabolic processes carried out by molecular complexes such as the ribosome. Much of the haploinsufficiency in YPD is alleviated by slowing the growth rate of each strain in minimal media, suggesting that certain gene products are rate limiting for growth only in YPD. Overall, our results suggest that the primary mechanism of haploinsufficiency in yeast is due to insufficient protein production. We discuss the relevance of our findings in yeast to human haploinsufficiency disorders.  相似文献   

7.
In genetic polymorphisms of two alleles, heterozygous individuals may contribute to the next generation on average more or fewer descendants than the homozygotes. Two different evolutionary responses that remove a disadvantageous heterozygote phenotype from the population are the evolution of strictly assortative mate choice, and that of a modifier making one of the two alleles completely dominant. We derive invasion fitness of mutants introducing dominance or assortative mate choice in a randomly mating population with a genetic polymorphism for an ecological trait. Mutations with small effects as well as mutants introducing complete dominance or perfect assorting are considered. Using adaptive dynamics techniques, we are able to calculate the ratio of fitness gradients for the effects of a dominance modifier and a mate choice locus, near evolutionary branching points. With equal resident allele frequencies, selection for mate choice is always stronger. Dominance is more strongly selected than assortative mating when the resident (common) alleles have very unequal frequencies at equilibrium. With female mate choice the difference in frequencies where dominance is more strongly selected is smaller than when mutants of both sexes can choose without costs. A symmetric resource-competition model illustrates the results.  相似文献   

8.
Zeyl C  DeVisser JA 《Genetics》2001,157(1):53-61
The per-genome, per-generation rate of spontaneous mutation affecting fitness (U) and the mean fitness cost per mutation (s) are important parameters in evolutionary genetics, but have been estimated for few species. We estimated U and sh (the heterozygous effect of mutations) for two diploid yeast strains differing only in the DNA mismatch-repair deficiency used to elevate the mutation rate in one (mutator) strain. Mutations were allowed to accumulate in 50 replicate lines of each strain, during 36 transfers of randomly chosen single colonies (approximately 600 generations). Among wild-type lines, fitnesses were bimodal, with one mode showing no change in mean fitness. The other mode showed a mean 29.6% fitness decline and the petite phenotype, usually caused by partial deletion of the mitochondrial genome. Excluding petites, maximum-likelihood estimates adjusted for the effect of selection were U = 9.5 x 10(-5) and sh = 0.217 for the wild type. Among the mutator lines, the best fit was obtained with 0.005 < or = U < or = 0.94 and 0.049 > or = sh > or = 0.0003. Like other recently tested model organisms, wild-type yeast have low mutation rates, with high mean fitness costs per mutation. Inactivation of mismatch repair increases the frequency of slightly deleterious mutations by approximately two orders of magnitude.  相似文献   

9.
Manna F  Martin G  Lenormand T 《Genetics》2011,189(3):923-937
Deleterious mutations tend to be recessive. Several theories, notably those of Fisher (based on selection) and Wright (based on metabolism), have been put forward to explain this pattern. Despite a long-lasting debate, the matter remains unresolved. This debate has focused on the average dominance of mutations. However, we also know very little about the distribution of dominance coefficients among mutations, and about its variation across environments. In this article we present a new approach to predicting this distribution. Our approach is based on a phenotypic fitness landscape model. First, we show that under a very broad range of conditions (and environments), the average dominance of mutation of small effects should be approximately one-quarter as long as adaptation of organisms to their environment can be well described by stabilizing selection on an arbitrary set of phenotypic traits. Second, the theory allows predicting the whole distribution of dominance coefficients among mutants. Because it provides quantitative rather than qualitative predictions, this theory can be directly compared to data. We found that its prediction on mean dominance (average dominance close to 0.25) agreed well with the data, based on a meta-analysis of dominance data for mildly deleterious mutations. However, a simple landscape model does not account for the dominance of mutations of large effects and we provide possible extension of the theory for this class of mutations. Because dominance is a central parameter for evolutionary theory, and because these predictions are quantitative, they set the stage for a wide range of applications and further empirical tests.  相似文献   

10.
Bioactive compounds are widely used to modulate protein function and can serve as important leads for drug development. Identifying the in vivo targets of these compounds remains a challenge. Using yeast, we integrated three genome-wide gene-dosage assays to measure the effect of small molecules in vivo. A single TAG microarray was used to resolve the fitness of strains derived from pools of (i) homozygous deletion mutants, (ii) heterozygous deletion mutants and (iii) genomic library transformants. We demonstrated, with eight diverse reference compounds, that integration of these three chemogenomic profiles improves the sensitivity and specificity of small-molecule target identification. We further dissected the mechanism of action of two protein phosphatase inhibitors and in the process developed a framework for the rational design of multidrug combinations to sensitize cells with specific genotypes more effectively. Finally, we applied this platform to 188 novel synthetic chemical compounds and identified both potential targets and structure-activity relationships.  相似文献   

11.
When alleles have pleiotropic effects on a number of quantitative traits, the degree of dominance between a pair of alleles can be different for each trait. Such trait-specific dominance has been studied previously in models for the maintenance of genetic variation by antagonistic effects of an allele on two fitness components. By generalizing these models to an arbitrary number of fitness components or other phenotypic traits with different degrees of dominance, I show that genetic polymorphism is generally impossible without antagonistic fitness effects of different traits and without trait-specific dominance. I also investigate dominance and pleiotropy from a more long-term evolutionary perspective, allowing for the study of general ecological scenarios, and I discuss the effects of trait-specific dominance on evolutionary stability criteria. When selection is mainly directional and only trait-specific dominance and antagonism cause the emergence of polymorphism, then these polymorphisms can be overtaken by single mutants again, such that they are probably short-lived on an evolutionary time scale. Near evolutionarily singular points where directional selection is absent, trait-specific dominance and overdominance facilitate the emergence of polymorphism and cause evolutionary divergence in some cases. An important outcome of these models is that trait-specific dominance allows for the emergence of genetic polymorphisms without a selective disadvantage for heterozygotes. This removes the scope for the evolution of assortative mate choice and affects dominance modification. Sympatric speciation by disruptive ecological selection requires this heterozygote disadvantage in order to evolve, and therefore it becomes less plausible if the emergence of genetic polymorphism usually occurs via trait-specific dominance and antagonistic effects.  相似文献   

12.
Integrating cooperative breeding into theoretical concepts of cooperation   总被引:2,自引:0,他引:2  
In cooperative breeding systems, some individuals help to raise offspring that are not their own. While early explanations for such altruistic behaviour were predominantly based on kin selection, recent evidence suggests that direct benefits may be important in the maintenance of cooperation. To date, however, discussions of cooperative breeding have made little reference to more general theories of cooperation between unrelated individuals (while these theories rarely address cooperative breeding). Here, we attempt to integrate the two fields. We identify four key questions that can be used to categorise different mechanisms for the maintenance of cooperative behaviour: (1) whether or not individuals invest in others; (2) whether or not this initial investment elicits a return investment by the beneficiary; (3) whether the interaction is direct, i.e. between two partners, or indirect (involving third parties) and (4) whether only actions that increase the fitness of the partner or also fitness reducing actions (punishment) are involved in the interaction. Asking these questions with regards to concepts in the literature on cooperative breeding, we found that (a) it is often straightforward to relate these concepts to general mechanisms of cooperation, but that (b) a single term (such as 'pay-to-stay', 'group augmentation' or 'prestige') may sometimes subsume two or more distinct mechanisms, and that (c) at least some mechanisms that are thought to be important in cooperative breeding systems have remained largely unexplored in the theoretical literature on the evolution of cooperation. Future theoretical models should incorporate asymmetries in power and pay off structure caused for instance by dominance hierarchies or partner choice, and the use of N-player games. The key challenges for both theoreticians and empiricists will be to integrate the hitherto disparate fields and to disentangle the parallel effects of kin and non-kin based mechanisms of cooperation.  相似文献   

13.
Brock MT  Tiffin P  Weinig C 《Molecular ecology》2007,16(14):3050-3062
Identifying the molecular genetic basis of intraspecific variation in quantitative traits promises to provide novel insight into their evolutionary history as well as genetic mechanisms of adaptation. In an attempt to identify genes responsible for natural variation in competitive responses in Arabidopsis thaliana, we examined DNA sequence diversity at seven loci previously identified as members of the phytochrome B signalling network. For one gene, GIGANTEA (GI), we detected significant haplotype structure. To test for GI haplogroup-phenotype associations, we genotyped 161 A. thaliana accessions at GI and censused the same accessions for total fruit set and the expression of three phenotypic traits (days to flowering, petiole length, and inflorescence height) in a greenhouse experiment where plants were grown in crowded and uncrowded environments. We detected a significant association between GI and total fruit set that resulted in a 14% difference in average fruit set among GI haplogroups. Given that fruit set is an important component of fitness in this species and given the magnitude of the effect, the question arises as to how variation at this locus is maintained. Our observation of frequent and significant epistasis between GI and background single nucleotide polymorphisms (SNP), where the fitness ranking of the GI allele either reverses or does not differ depending on the allele at the interacting SNP, suggests that epistatic selection may actively maintain or at least slow the loss of variation at GI. This result is particularly noteworthy in the light of the ongoing debate regarding the genetic underpinnings of phenotypic evolution and recent observations that epistasis for phenotypic traits and components of fitness is common in A. thaliana.  相似文献   

14.
This theme issue has highlighted the links between sociality, health and fitness in a broad range of organisms, and with approaches that include field and captive studies of animals, comparative and meta-analyses, theoretical modelling and clinical and psychological studies of humans. In this concluding chapter, we synthesize the results of these diverse studies into some of the key concepts discussed in this issue, focusing on risks of infectious disease through social contact, the effects of competition in groups on susceptibility to disease, and the integration of sociality into research on life-history trade-offs. Interestingly, the studies in this issue both support pre-existing hypotheses, and in other ways challenge those hypotheses. We focus on unexpected results, including a lack of association between ectoparasites and fitness and weak results from a meta-analysis of the links between dominance rank and immune function, and place these results in a broader context. We also review relevant topics that were not covered fully in this theme issue, including self-medication and sickness behaviours, society-level defences against infectious disease, sexual selection, evolutionary medicine, implications for conservation biology and selective pressures on parasite traits. We conclude by identifying general open questions to stimulate and guide future research on the links between sociality, health and fitness.  相似文献   

15.
Adaptive Dynamics is an approach to studying evolutionary change when fitness is density or frequency dependent. Modern papers identifying themselves as using this approach first appeared in the 1990s, and have greatly increased up to the present. However, because of the rather technical nature of many of the papers, the approach is not widely known or understood by evolutionary biologists. In this review we aim to remedy this situation by outlining the methodology and then examining its strengths and weaknesses. We carry this out by posing and answering 20 key questions on Adaptive Dynamics. We conclude that Adaptive Dynamics provides a set of useful approximations for studying various evolutionary questions. However, as with any approximate method, conclusions based on Adaptive Dynamics are valid only under some restrictions that we discuss.  相似文献   

16.
Molecular evolutionary theory predicts that the ratio of autosomal to X-linked adaptive substitution (K(A)/K(x)) is primarily determined by the average dominance coefficient of beneficial mutations. Although this theory has profoundly influenced analysis and interpretation of comparative genomic data, its predictions are based upon two unverified assumptions about the genetic basis of adaptation. The theory assumes that 1) the rate of adaptively driven molecular evolution is limited by the availability of beneficial mutations, and 2) the scaling of evolutionary parameters between the X and the autosomes (e.g., the beneficial mutation rate, and the fitness effect distribution of beneficial alleles, per X-linked versus autosomal locus) is constant across molecular evolutionary timescales. Here, we show that the genetic architecture underlying bouts of adaptive substitution can influence both assumptions, and consequently, the theoretical relationship between K(A)/K(x) and mean dominance. Quantitative predictions of prior theory apply when 1) many genomically dispersed genes potentially contribute beneficial substitutions during individual steps of adaptive walks, and 2) the population beneficial mutation rate, summed across the set of potentially contributing genes, is sufficiently small to ensure that adaptive substitutions are drawn from new mutations rather than standing genetic variation. Current research into the genetic basis of adaptation suggests that both assumptions are plausibly violated. We find that the qualitative positive relationship between mean dominance and K(A)/K(x) is relatively robust to the specific conditions underlying adaptive substitution, yet the quantitative relationship between dominance and K(A)/K(x) is quite flexible and context dependent. This flexibility may partially account for the puzzlingly variable X versus autosome substitution patterns reported in the empirical evolutionary genomics literature. The new theory unites the previously separate analysis of adaptation using new mutations versus standing genetic variation and makes several useful predictions about the interaction between genetic architecture, evolutionary genetic constraints, and effective population size in determining the ratio of adaptive substitution between autosomal and X-linked genes.  相似文献   

17.
Autolysis of Saccharomyces cerevisiae is the main source of molecules that contribute to the quality of sparkling wines made by the traditional method. In this work the possibility of accelerating this slow process in order to improve the quality of sparkling wines by using genetically engineered wine yeast strains was explored. The effect of partial or total deletion of BCY1 (which encodes a regulatory subunit of cAMP-dependent protein kinase A) in haploid and diploid (heterozygous and homozygous) yeast strains was studied. We proved that heterozygous strains having partial or complete BCY1 deletions have a semidominant phenotype for several of the properties studied, including autolysis under simulated second-fermentation conditions, in contrast to previously published reports describing mutations in BCY1 as recessive. Considering the degree of autolysis, ethanol tolerance, and technical feasibility, we propose that deletion of the 3' end of the open reading frame of a single copy of BCY1 is a way to improve the quality of sparkling wines.  相似文献   

18.
The Evolutionary Studies (EvoS) Consortium and the academic programs born from its creation have been wildly successful in their initial ventures. These achievements are marked by feedback from across the EvoS campuses, the resultant scholarly work produced by participating students, and faculty collaborations spurred by exposure to the organization. The success of EvoS is probably best marked by the recent National Science Foundation grant (CCLI Award #0817337), awarded jointly to SUNY New Paltz and Binghamton University, with the purpose of expanding EvoS beyond the bounds of these two institutions. A particularly noteworthy element of many EvoS programs is the role of Evolutionary Psychology (EP), a perspective in the behavioral sciences that addresses questions of human behavior from the perspective of evolution. In light of several forms of data, including analyses of a variety of disciplines drawn on from evolutionary psychologists in their work, we argue that evolutionary psychologists may well be the most naturally interdisciplinary scholars within the behavioral sciences, making them highly appropriate for inclusion in EvoS. But our research shows not only promise regarding the relationship between EP and EvoS—challenges are raised as well. We present additional data showing that EP is currently represented disproportionately within the EvoS world—a fact that clearly shows that there are currently limitations to the potential impact of EvoS in modern academia. Scholars from other disciplines, particularly within the humanities and social sciences, seem to be missing the evolution revolution. Implications regarding how EvoS can broaden its scope to be even more powerful in its integrative scope are discussed.  相似文献   

19.
The lack of association between wealth and fertility in contemporary industrialized populations has often been used to question the value of an evolutionary perspective on human behaviour. Here, we first present the history of this debate, and the evolutionary explanations for why wealth and fertility (the number of children) are decoupled in modern industrial settings. We suggest that the nature of the relationship between wealth and fertility remains an open question because of the multi-faceted nature of wealth, and because existing cross-sectional studies are ambiguous with respect to how material wealth and fertility are linked. A literature review of longitudinal studies on wealth and fertility shows that the majority of these report positive effects of wealth, although levels of fertility seem to fall below those that would maximize fitness. We emphasize that reproductive decision-making reflects a complex interplay between individual and societal factors that resists simple evolutionary interpretation, and highlight the role of economic insecurity in fertility decisions. We conclude by discussing whether the wealth–fertility relationship can inform us about the adaptiveness of modern fertility behaviour, and argue against simplistic claims regarding maladaptive behaviour in humans.  相似文献   

20.
In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait–fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号