Epistasis can increase multivariate trait diversity in haploid non-recombining populations

We evaluate the effect of epistasis on genetically-based multivariate trait variation in haploid non-recombining populations. In a univariate setting, past work has shown that epistasis reduces genetic variance (additive plus epistatic) in a population experiencing stabilizing selection. Here we show that in a multivariate setting, epistasis also reduces total genetic variation across the entire multivariate trait in a population experiencing stabilizing selection. But, we also show that the pattern of variation across the multivariate trait can be more even when epistasis occurs compared to when epistasis is absent, such that some character combinations will have more genetic variance when epistasis occurs compared to when epistasis is absent. In fact, a measure of generalized multivariate trait variation can be increased by epistasis under weak to moderate stabilizing selection conditions, as well as neutral conditions. Likewise, a measure of conditional evolvability can be increased by epistasis under weak to moderate stabilizing selection and neutral conditions. We investigate the nature of epistasis assuming a multivariate-normal model genetic effects and investigate the nature of epistasis underlying the biophysical properties of RNA. Increased multivariate diversity occurs for populations that are infinite in size, as well as populations that are finite in size. Our model of finite populations is explicitly genealogical and we link our findings about the evenness of eigenvalues with epistasis to prior work on the genealogical mapping of epistatic effects.     

Competition both drives and impedes diversification in a model adaptive radiation

Competitors are known to be important in governing the outcome of evolutionary diversification during an adaptive radiation, but the precise mechanisms by which they exert their effects remain elusive. Using the model adaptive radiation of Pseudomonas fluorescens, we show experimentally that the effect of competition on diversification of a focal lineage depends on both the strength of competition and the ability of the competitors to diversify. We provide evidence that the extent of diversification in the absence of interspecific competitors depends on the strength of resource competition. We also show that the presence of competitors can actually increase diversity by increasing interspecific resource competition. Competitors that themselves are able to diversify prevent diversification of the focal lineage by removing otherwise available ecological opportunities. These results suggest that the progress of an adaptive radiation depends ultimately on the strength of resource competition, an effect that can be exaggerated or impeded by the presence of competitors.     

Epistasis in natural populations of a predominantly selfing plant

Populations of predominantly selfing plant species often show spatial genetic structure but little is known whether epistatic gene interactions are spatially structured. To detect a possible epistatic effect and a spatial scale at which it operates, we created artificial crosses between plants spanning a range of fixed distances from 1 to 400 m in three populations of wild barley. The self-pollinated and crossed progeny (F₁) and two generations of segregated progeny (F₂ and F₃) were tested in experimentally simulated population environments for relative performance (RP). The measured fitness traits included number of seeds, total seed weight and seed germination. For any of these traits, there was no association between RP of F₁, F₂ and F₃ plants and either pairwise kinship coefficients or crossing distance. In contrast, in all three populations, we found lower seed viability of outcrossed as compared with self-pollinated genotypes in the first generation of segregation. However, in the F₃ generation this outbreeding effect disappeared in the two populations and greatly decreased in the third population. For seed production, heterosis in F₁ and outbreeding depression in F₂ were observed only in the population with unusually high number of heterozygotes. Our findings support the view that in selfing species a spatial mosaic of various locally abundant genotypes represents not randomly fixed combinations of alleles but the co-adapted gene complexes that were sieved by selection, while heterozygotes are characteristic for the transient phase of this process, when segregation and purging of maladaptive genotypes have not yet occurred.     

Epistasis and frequency dependence influence the fitness of an adaptive mutation in a diversifying lineage

The opportunity for a mutation to invade a population can dramatically vary depending on the context in which this mutation occurs. Such context dependence is difficult to document as it requires the ability to measure how a mutation affects phenotypes and fitness and to manipulate the context in which the mutation occurs. We identified a mutation in a gene encoding a global regulator in one of two ecotypes that diverged from a common ancestor during 1200 generations of experimental evolution. We replaced the ancestral allele by the mutant allele, and vice versa, in several clones isolated during the time course of the evolution experiment, and compared the phenotype and fitness of clones isogenic except for the focal mutation. We show that the fitness and phenotype of the mutation are strongly affected by epistatic interactions between genes in the same genome, as well as by frequency dependent selection resulting from biotic interactions between individuals in the same population. We conclude that amongst the replicate population in which it spread, the mutation we identified is only adaptive when occurring in specific genomes and competing with specific individuals. This study thus demonstrates that the opportunity for an adaptive mutation to spread in an evolutionary lineage can only be understood in the light of its genomic and competitive environments.     

Population subdivision and adaptation in asexual populations of Saccharomyces cerevisiae

Population subdivision limits competition between individuals, which can have a profound effect on adaptation. Subdivided populations maintain more genetic diversity at any given time compared to well-mixed populations, and thus "explore" larger parts of the genotype space. At the same time, beneficial mutations take longer to spread in such populations, and thus subdivided populations do not "exploit" discovered mutations as efficiently as well-mixed populations. Whether subdivision inhibits or promotes adaptation in a given environment depends on the relative importance of exploration versus exploitation, which in turn depends on the structure of epistasis among beneficial mutations. Here we investigate the relative importance of exploration versus exploitation for adaptation by evolving 976 independent asexual populations of budding yeast with several degrees of geographic subdivision. We find that subdivision systematically inhibits adaptation: even the luckiest demes in subdivided populations on average fail to discover genotypes that are fitter than those discovered by well-mixed populations. Thus, exploitation of discovered mutations is more important for adaptation in our system than a thorough exploration of the mutational neighborhood, and increasing subdivision slows adaptation.     

Evidence for determinism in species diversification and contingency in phenotypic evolution during adaptive radiation

Adaptive radiation (AR) theory predicts that groups sharing the same source of ecological opportunity (EO) will experience deterministic species diversification and morphological evolution. Thus, deterministic ecological and morphological evolution should be correlated with deterministic patterns in the tempo and mode of speciation for groups in similar habitats and time periods. We test this hypothesis using well-sampled phylogenies of four squamate groups that colonized the New World (NW) in the Late Oligocene. We use both standard and coalescent models to assess species diversification, as well as likelihood models to examine morphological evolution. All squamate groups show similar early pulses of speciation, as well as diversity-dependent ecological limits on clade size at a continental scale. In contrast, processes of morphological evolution are not easily predictable and do not show similar pulses of early and rapid change. Patterns of morphological and species diversification thus appear uncoupled across these groups. This indicates that the processes that drive diversification and disparification are not mechanistically linked, even among similar groups of taxa experiencing the same sources of EO. It also suggests that processes of phenotypic diversification cannot be predicted solely from the existence of an AR or knowledge of the process of diversification.     

Relevance of Higher-Order Epistasis in Drug Resistance

We studied five chemically distinct but related 1,3,5-triazine antifolates with regard to their effects on growth of a set of mutants in dihydrofolate reductase. The mutants comprise a combinatorially complete data set of all 16 possible combinations of four amino acid replacements associated with resistance to pyrimethamine in the malaria parasite Plasmodium falciparum. Pyrimethamine was a mainstay medication for malaria for many years, and it is still in use in intermittent treatment during pregnancy or as a partner drug in artemisinin combination therapy. Our goal was to investigate the extent to which the alleles yield similar adaptive topographies and patterns of epistasis across chemically related drugs. We find that the adaptive topographies are indeed similar with the same or closely related alleles being fixed in computer simulations of stepwise evolution. For all but one of the drugs the topography features at least one suboptimal fitness peak. Our data are consistent with earlier results indicating that third order and higher epistatic interactions appear to contribute only modestly to the overall adaptive topography, and they are largely conserved. In regard to drug development, our data suggest that higher-order interactions are likely to be of little value as an advisory tool in the choice of lead compounds.     

Epistasis can lead to fragmented neutral spaces and contingency in evolution

In evolution, the effects of a single deleterious mutation can sometimes be compensated for by a second mutation which recovers the original phenotype. Such epistatic interactions have implications for the structure of genome space--namely, that networks of genomes encoding the same phenotype may not be connected by single mutational moves. We use the folding of RNA sequences into secondary structures as a model genotype-phenotype map and explore the neutral spaces corresponding to networks of genotypes with the same phenotype. In most of these networks, we find that it is not possible to connect all genotypes to one another by single point mutations. Instead, a network for a phenotypic structure with n bonds typically fragments into at least 2(n) neutral components, often of similar size. While components of the same network generate the same phenotype, they show important variations in their properties, most strikingly in their evolvability and mutational robustness. This heterogeneity implies contingency in the evolutionary process.     

Spatially heterogeneous stochasticity and the adaptive diversification of dormancy

Diversified bet‐hedging, a strategy that leads several individuals with the same genotype to express distinct phenotypes in a given generation, is now well established as a common evolutionary response to environmental stochasticity. Life‐history traits defined as diversified bet‐hedging (e.g. germination or diapause strategies) display marked differences between populations in spatial proximity. In order to find out whether such differences can be explained by local adaptations to spatially heterogeneous environmental stochasticity, we explored the evolution of bet‐hedging dormancy strategies in a metapopulation using a two‐patch model with patch differences in stochastic juvenile survival. We found that spatial differences in the level of environmental stochasticity, restricted dispersal, increased fragmentation and intermediate survival during dormancy all favour the adaptive diversification of bet‐hedging dormancy strategies. Density dependency also plays a major role in the diversification of dormancy strategies because: (i) it may interact locally with environmental stochasticity and amplify its effects; however, (ii) it can also generate chaotic population dynamics that may impede diversification. Our work proposes new hypotheses to explain the spatial patterns of bet‐hedging strategies that we hope will encourage new empirical studies of this topic.     

Biogeography of species richness gradients: linking adaptive traits,demography and diversification

Here we review how adaptive traits contribute to the emergence and maintenance of species richness gradients through their influence on demographic and diversification processes. We start by reviewing how demographic dynamics change along species richness gradients. Empirical studies show that geographical clines in population parameters and measures of demographic variability are frequent along latitudinal and altitudinal gradients. Demographic variability often increases at the extremes of regional species richness gradients and contributes to shape these gradients. Available studies suggest that adaptive traits significantly influence demographic dynamics, and set the limits of species distributions. Traits related to thermal tolerance, resource use, phenology and dispersal seem to play a significant role. For many traits affecting demography and/or diversification processes, complex mechanistic approaches linking genotype, phenotype and fitness are becoming progressively available. In several taxa, species can be distributed along adaptive trait continuums, i.e. a main axis accounting for the bulk of inter‐specific variation in some correlated adaptive traits. It is shown that adaptive trait continuums can provide useful mechanistic frameworks to explain demographic dynamics and diversification in species richness gradients. Finally, we review the existence of sequences of adaptive traits in phylogenies, the interactions of adaptive traits and community context, the clinal variation of traits across geographical gradients, and the role of adaptive traits in determining the history of dispersal and diversification of clades. Overall, we show that the study of demographic and evolutionary mechanisms that shape species richness gradients clearly requires the explicit consideration of adaptive traits. To conclude, future research lines and trends in the field are briefly outlined.     

Morphological innovation, diversification and invasion of a new adaptive zone

How ecological opportunity relates to diversification is a central question in evolutionary biology. However, there are few empirical examples of how ecological opportunity and morphological innovation open new adaptive zones, and promote diversification. We analyse data on diet, skull morphology and bite performance, and relate these traits to diversification rates throughout the evolutionary history of an ecologically diverse family of mammals (Chiroptera: Phyllostomidae). We found a significant increase in diversification rate driven by increased speciation at the most recent common ancestor of the predominantly frugivorous subfamily Stenodermatinae. The evolution of diet was associated with skull morphology, and morphology was tightly coupled with biting performance, linking phenotype to new niches through performance. Following the increase in speciation rate, the rate of morphological evolution slowed, while the rate of evolution in diet increased. This pattern suggests that morphology stabilized, and niches within the new adaptive zone of frugivory were filled rapidly, after the evolution of a new cranial phenotype that resulted in a certain level of mechanical efficiency. The tree-wide speciation rate increased non linearly with a more frugivorous diet, and was highest at measures of skull morphology associated with morphological extremes, including the most derived Stenodermatines. These results show that a novel stenodermatine skull phenotype played a central role in the evolution of frugivory and increasing speciation within phyllostomids.     

Evolution of niche width and adaptive diversification

Theoretical models suggest that resource competition can lead to the adaptive splitting of consumer populations into diverging lineages, that is, to adaptive diversification. In general, diversification is likely if consumers use only a narrow range of resources and thus have a small niche width. Here we use analytical and numerical methods to study the consequences for diversification if the niche width itself evolves. We found that the evolutionary outcome depends on the inherent costs or benefits of widening the niche. If widening the niche did not have costs in terms of overall resource uptake, then the consumer evolved a niche that was wide enough for disruptive selection on the niche position to vanish; adaptive diversification was no longer observed. However, if widening the niche was costly, then the niche widths remained relatively narrow, allowing for adaptive diversification in niche position. Adaptive diversification and speciation resulting from competition for a broadly distributed resource is thus likely if the niche width is fixed and relatively narrow or free to evolve but subject to costs. These results refine the conditions for adaptive diversification due to competition and formulate them in a way that might be more amenable for experimental investigations.     

Ecological opportunity and the adaptive diversification of lineages

The tenet that ecological opportunity drives adaptive diversification has been central to theories of speciation since Darwin, yet no widely accepted definition or mechanistic framework for the concept currently exists. We propose a definition for ecological opportunity that provides an explicit mechanism for its action. In our formulation, ecological opportunity refers to environmental conditions that both permit the persistence of a lineage within a community, as well as generate divergent natural selection within that lineage. Thus, ecological opportunity arises from two fundamental elements: (1) niche availability, the ability of a population with a phenotype previously absent from a community to persist within that community and (2) niche discordance, the diversifying selection generated by the adaptive mismatch between a population's niche‐related traits and the newly encountered ecological conditions. Evolutionary response to ecological opportunity is primarily governed by (1) spatiotemporal structure of ecological opportunity, which influences dynamics of selection and development of reproductive isolation and (2) diversification potential, the biological properties of a lineage that determine its capacity to diversify. Diversification under ecological opportunity proceeds as an increase in niche breadth, development of intraspecific ecotypes, speciation, and additional cycles of diversification that may themselves be triggered by speciation. Extensive ecological opportunity may exist in depauperate communities, but it is unclear whether ecological opportunity abates in species‐rich communities. Because ecological opportunity should generally increase during times of rapid and multifarious environmental change, human activities may currently be generating elevated ecological opportunity – but so far little work has directly addressed this topic. Our framework highlights the need for greater synthesis of community ecology and evolutionary biology, unifying the four major components of the concept of ecological opportunity.     

上位性及其在遗传育种研究中的应用

上位性引入遗传学已有一个多世纪,直到近些年才受到广泛关注,成为复杂性状遗传研究体系的一个重要组成部分。上位性可分为统计上位性和功能上位性两类,前者具有群体特性,后者属于基因型现象。分子标记技术是研究上位性的一个有力工具,理论与实验研究证实上位性在动植物数量性状的表现中具有重要作用。上位性在作物育种中的应用因作物的繁殖方式,育种方法等不同而异,上位性是杂种优势形成的重要遗传基础。     

Density-dependent diversification in North American wood warblers

Evidence from both molecular phylogenies and the fossil record suggests that rates of species diversification often decline through time during evolutionary radiations. One proposed explanation for this pattern is ecological opportunity, whereby an initial abundance of resources and lack of potential competitors facilitate rapid diversification. This model predicts density-dependent declines in diversification rates, but has not been formally tested in any species-level radiation. Here we develop a new conceptual framework that distinguishes density dependence from alternative processes that also produce temporally declining diversification, and we demonstrate this approach using a new phylogeny of North American Dendroica wood warblers. We show that explosive lineage accumulation early in the history of this avian radiation is best explained by a density-dependent diversification process. Our results suggest that the tempo of wood warbler diversification was mediated by ecological interactions among species and that lineage and ecological diversification in this group are coupled, as predicted under the ecological opportunity model.     

Epistasis in the multiple locus symmetric viability model

The n-locus two-allele symmetric viability model is considered in terms of the parameters measuring the additive epistasis in fitness. The dynamics is analysed using a simple linear transformation of the gametic frequencies, and then the recurrence equations depend on the epistatic parameters and Geiringer's recombination distribution only. The model exhibits an equilibrium, the central equilibrium, where the 2 ⁿ gametes are equally frequent. The transformation simplifies the stability analysis of the central point, and provides the stability conditions in terms of the existence conditions of other equilibria. For total negative epistasis (all epistatic parameters are negative) the central point is stable for all recombination distributions. For free recombination either a central point (segregating one, two, ... or n loci) or the n-locus fixation states are stable. For no recombination and some epistatic parameters positive the central point is unstable and several boundary equilibria may be locally stable. The sign structure of the additive epistasis is therefore an important determinant of the dynamics of the n-locus symmetric viability model. The non-symmetric multiple locus models previously analysed are dynamically related, and they all have an epistatic sign structure that resembles that of the multiplicative viability model. A non-symmetric model with total negative epistasis which share dynamical properties with the similar symmetric model is suggested.Supported in part by NIH grant GM 28016, and by grant 81-5458 from the Danish Natural Science Research Council     

Epistasis affecting litter size in mice

Litter size is an important reproductive trait as it makes a major contribution to fitness. Generally, traits closely related to fitness show low heritability perhaps because of the corrosive effects of directional natural selection on the additive genetic variance. Nonetheless, low heritability does not imply, necessarily, a complete absence of genetic variation because genetic interactions (epistasis and dominance) contribute to variation in traits displaying strong heterosis in crosses, such as litter size. In our study, we investigated the genetic architecture of litter size in 166 females from an F2 intercross of the SM/J and LG/J inbred mouse strains. Litter size had a low heritability (h2 = 12%) and a low repeatability (r = 33%). Using interval-mapping methods, we located two quantitative trait loci (QTL) affecting litter size at locations D7Mit21 + 0 cM and D12Mit6 + 8 cM, on chromosomes 7 and 12 respectively. These QTL accounted for 12.6% of the variance in litter size. In a two-way genome-wide epistasis scan we found eight QTL interacting epistatically involving chromosomes 2, 4, 5, 11, 14, 15 and 18. Taken together, the QTL and their interactions explain nearly 49% (39.5% adjusted multiple r2) of the phenotypic variation for litter size in this cross, an increase of 36% over the direct effects of the QTL. This indicates the importance of epistasis as a component of the genetic architecture of litter size and fitness in our intercross population.