A highly unexpected strong correlation between fixation probability of nonsynonymous mutations and mutation rate

Under prevailing theories, the nonsynonymous-to-synonymous substitution ratio (i.e. K(a)/K(s)), which measures the fixation probability of nonsynonymous mutations, is correlated with the strength of selection. In this article, we report that K(a)/K(s) is also strongly correlated with the mutation rate as measured by K(s), and that this correlation appears to have a similar magnitude as the correlation between K(a)/K(s) and selective strength. This finding cannot be reconciled with current theories. It suggests that we should re-evaluate the current paradigms of coding-sequence evolution, and that the wide use of K(a)/K(s) as a measure of selective strength needs reassessment.     

Genetic covariance structure of growth in the salamander Ambystoma macrodactylum

The size of an organism at any point during ontogeny often has fitness consequences through either direct selection on size or through selection on size-related morphological, performance, or life history traits. However, the evolutionary response to selection on size across ontogeny (a growth trajectory) may be limited by genetic correlations across ages. Here we characterize the phenotypic and genetic covariance structure of length and mass growth trajectories in a natural population of larval Ambystoma macrodactylum using function-valued quantitative genetic analyses and principal component decomposition. Most of the phenotypic and genetic variation in both growth trajectories appears to be confined to a single principal component describing a pattern of positive covariation among sizes across all ages. Higher order principal components with no significant associated genetic variation were identified for both trajectories, suggesting that evolution towards certain patterns of negative covariation between sizes across ages is constrained. The well-characterized positive relationship between size at metamorphosis and fitness in pond-breeding amphibians predicts that the across-age covariance structure will strongly limit evolution only if there is negative selection on size prior to metamorphosis. The pattern of genetic covariation observed in this study is similar to that observed in other vertebrate taxa, indicating that size may often be highly genetically and phenotypically integrated across ontogeny. Additionally, we find that phenotypic and genetic analyses of growth trajectories can yield qualitatively similar patterns of covariance structure.     

Morpho morphometrics: Shared ancestry and selection drive the evolution of wing size and shape in Morpho butterflies

Butterfly wings harbor highly diverse phenotypes and are involved in many functions. Wing size and shape result from interactions between adaptive processes, phylogenetic history, and developmental constraints, which are complex to disentangle. Here, we focus on the genus Morpho (Nymphalidae: Satyrinae, 30 species), which presents a high diversity of sizes, shapes, and color patterns. First, we generate a comprehensive molecular phylogeny of these 30 species. Next, using 911 collection specimens, we quantify the variation of wing size and shape across species, to assess the importance of shared ancestry, microhabitat use, and sexual selection in the evolution of the wings. While accounting for phylogenetic and allometric effects, we detect a significant difference in wing shape but not size among microhabitats. Fore and hindwings covary at the individual and species levels, and the covariation differs among microhabitats. However, the microhabitat structure in covariation disappears when phylogenetic relationships are taken into account. Our results demonstrate that microhabitat has driven wing shape evolution, although it has not strongly affected forewing and hindwing integration. We also found that sexual dimorphism of forewing shape and color pattern are coupled, suggesting a common selective force.     

The evolution of phenotypic integration: How directional selection reshapes covariation in mice

Variation is the basis for evolution, and understanding how variation can evolve is a central question in biology. In complex phenotypes, covariation plays an even more important role, as genetic associations between traits can bias and alter evolutionary change. Covariation can be shaped by complex interactions between loci, and this genetic architecture can also change during evolution. In this article, we analyzed mouse lines experimentally selected for changes in size to address the question of how multivariate covariation changes under directional selection, as well as to identify the consequences of these changes to evolution. Selected lines showed a clear restructuring of covariation in their cranium and, instead of depleting their size variation, these lines increased their magnitude of integration and the proportion of variation associated with the direction of selection. This result is compatible with recent theoretical works on the evolution of covariation that take the complexities of genetic architecture into account. This result also contradicts the traditional view of the effects of selection on available covariation and suggests a much more complex view of how populations respond to selection.     

Trends in prokaryotic evolution revealed by comparison of closely related bacterial and archaeal genomes

In order to explore microevolutionary trends in bacteria and archaea, we constructed a data set of 41 alignable tight genome clusters (ATGCs). We show that the ratio of the medians of nonsynonymous to synonymous substitution rates (dN/dS) that is used as a measure of the purifying selection pressure on protein sequences is a stable characteristic of the ATGCs. In agreement with previous findings, parasitic bacteria, notwithstanding the sometimes dramatic genome shrinkage caused by gene loss, are typically subjected to relatively weak purifying selection, presumably owing to relatively small effective population sizes and frequent bottlenecks. However, no evidence of genome streamlining caused by strong selective pressure was found in any of the ATGCs. On the contrary, a significant positive correlation between the genome size, as well as gene size, and selective pressure was observed, although a variety of free-living prokaryotes with very close selective pressures span nearly the entire range of genome sizes. In addition, we examined the connections between the sequence evolution rate and other genomic features. Although gene order changes much faster than protein sequences during the evolution of prokaryotes, a strong positive correlation was observed between the “rearrangement distance” and the amino acid distance, suggesting that at least some of the events leading to genome rearrangement are subjected to the same type of selective constraints as the evolution of amino acid sequences.     

Reduced phenotypic covariation in marsupial limbs and the implications for mammalian evolution

As serially homologous structures, mammalian fore‐ and hindlimbs ancestrally share a common developmental and genetic architecture. As a result, mammalian fore‐ and hindlimbs are predicted to be highly integrated in the absence of selective pressures to form divergent limb morphologies. Marsupials experience such a divergent selective pressure to form a robust forelimb to power a post‐natal crawl to the teat. In this study, phenotypic covariation in marsupials was assessed to determine if specialization for the crawl did indeed reduce integration between their fore‐ and hindlimbs. To explore the evolution of mammalian limb integration, phenotypic covariation in representative eutherians and monotremes was also examined. Phenotypic covariation in limbs was quantified morphometrically, and analysed with correlational and phylogenetic methods. Results indicate that marsupials generally have relatively high levels of within‐limb phenotypic covariation, and low levels between limbs, in contrast to the pattern reconstructed for the mammalian ancestor. Our findings support the hypothesis that pressure to specialize in one limb (either the fore‐ or the hindlimb) can reduce phenotypic covariation between limbs, and that reduced limb phenotypic covariation is derived in marsupials. Further research is needed to test the effect that these differences in limb phenotypic covariation had on the evolution of the major mammalian groups. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 102 , 22–36.     

Contrasting covariation of above- and belowground invertebrate species across plant genotypes

1. Invertebrate species generally do not respond independently to genotypic variation in plants, giving rise to clusters of species that naturally associate with or avoid certain genotypes. This covariation causes coevolution to be diffuse rather than pairwise. Studies on this topic, however, have never considered the belowground invertebrate community, leaving a critical gap in our understanding. 2. We investigated the covariation among naturally colonising above- and belowground invertebrate species across six genetically distinct populations of the dune grass Ammophila arenaria. After having grown from seed in a common garden, plants were randomised in a single field site to exclude all but broad-sense genetic variation. 3. Strong positive covariation across genotypes among both above- and belowground invertebrates was detected, while correlations between these two groups were negative. This clustering of above- and belowground species matched well with order level taxonomy. Host range, trophic level and food type on the other hand did not correspond well with the clusters. Within the cluster of aboveground fauna, subsequent groupings were not related to any phylogenetic or ecological characteristic, although correlations within these subgroups were very high. We furthermore demonstrated significant differences in multiple invertebrate species occurrence between plant genotypes, in general as well as at the above- and belowground level. 4. The observed strong covariation suggests diffuse coevolution between A. arenaria and its associated invertebrate species. The trade-off between root and shoot invertebrates could however hamper directional selection on resistance to either group. 5. Our results clearly demonstrate the need for studies of plant-animal interactions to include the belowground fauna, as this might drastically alter our general conception of how plants and their associated animal communities interact and how these interactions shape the process of evolution.     

Covariation among floral traits in Spergularia marina (Caryophyllaceae): geographic and temporal variation in phenotypic and among-family correlations

Strong covariation among traits suggests the presence of constraints on their independent evolution due to pleiotropy, to linkage, or to selective forces that maintain particular trait combinations. We examined floral trait covariation among individuals, among maternal families within and across populations, and over time, in greenhouse-raised plants of the autogamous Spergularia marina. We had three aims. First, since the phenotype of traits expressed by modular organs often changes as individuals age, estimates of the degree of genetic covariation between such traits may also change over time. To seek evidence for this, we measured weekly (for five weeks) an array of floral traits among plants representing ～ 10 maternal families from each of four populations. The statistical significance of the phenotypic and among-family correlations among traits changed over time. Second, we compared populations with respect to trait covariation to determine whether populations or traits appear to be evolving independently of one another. Differences observed among populations suggest that they have diverged genetically. Third, we sought correlations that might reflect constraints on the independent evolution of floral traits. Investment in another and ovule production per flower vary independently among maternal families; there was no evidence for a “trade-off” between male and female investment. We propose that in autogamous taxa one should not find a negative correlation between pollen and ovule production per flower, as such taxa cannot evolve sexual specialization and should be under strong selection to maintain an efficient pollen:ovule ratio, preventing the evolution of male-biased or female-biased genotypes. We found that other pairs of floral traits, however, expressed highly signficant correlation coefficients, suggesting the presence of some evolutionary constraints, at least within some populations, although their strength depended on exactly when flowers were sampled.     

Why the short face? Developmental disintegration of the neurocranium drives convergent evolution in neotropical electric fishes

Convergent evolution is widely viewed as strong evidence for the influence of natural selection on the origin of phenotypic design. However, the emerging evo‐devo synthesis has highlighted other processes that may bias and direct phenotypic evolution in the presence of environmental and genetic variation. Developmental biases on the production of phenotypic variation may channel the evolution of convergent forms by limiting the range of phenotypes produced during ontogeny. Here, we study the evolution and convergence of brachycephalic and dolichocephalic skull shapes among 133 species of Neotropical electric fishes (Gymnotiformes: Teleostei) and identify potential developmental biases on phenotypic evolution. We plot the ontogenetic trajectories of neurocranial phenotypes in 17 species and document developmental modularity between the face and braincase regions of the skull. We recover a significant relationship between developmental covariation and relative skull length and a significant relationship between developmental covariation and ontogenetic disparity. We demonstrate that modularity and integration bias the production of phenotypes along the brachycephalic and dolichocephalic skull axis and contribute to multiple, independent evolutionary transformations to highly brachycephalic and dolichocephalic skull morphologies.     

Constraints on evolution and postcopulatory sexual selection: trade-offs among ejaculate characteristics

Ejaculates function as an integrated unit to ensure male fertility and paternity, can have a complex structure, and can experience multiple episodes of selection. Current studies on the evolution of ejaculates typically focus on phenotypic variation in sperm number, size, or related traits such as testes size as adaptations to postcopulatory male-male competition. However, the evolution of the integrated nature of ejaculate structure and function depends on genetic variation in and covariation between the component parts. Here we report a quantitative genetic study of the components of the ejaculate of the cockroach Nauphoeta cinerea, including those we know to experience postcopulatory sexual selection, in the context of functional integration of ejaculate characters. We use the patterns of genetic variation and covariation to infer how the integration of the functions of the ejaculate constrain and shape its evolution. Ejaculate components were highly variable, showed significant additive genetic variance, and moderate to high evolvability. The level of genetic variation in these characters, despite strong directional or truncating selection, may reflect the integration of multiple episodes of selection that occur in N. cinerea. There were few significant phenotypic correlations, but all the genetic correlations among ejaculate characters were significantly different from zero. The patterns of genetic variation and covariation suggest that there are important trade-offs among individual traits of the ejaculate and that evolution of ejaculate characteristics will not proceed unconstrained. Fully describing the genetic relationships among traits that perform as an integrated unit helps us understand how functional relationships constrain or facilitate the evolution of the complex structure that is the ejaculate.     

The Genetic Covariance between Characters Maintained by Pleiotropic Mutations

A statistical genetic model of a multivariate phenotype is derived to investigate the covariation of pleiotropic mutations with additive effects under the combined action of phenotypic selection, linkage and the mating system. Equilibrium formulas for large, randomly mating populations demonstrate that, when selection on polygenic variation is much smaller than twice the harmonic mean recombination rate between loci with interacting fitnesses, linkage disequilibrium is negligible and pleiotropy is the main cause of genetic correlations between characters. Under these conditions, approximate expressions for the dynamics of the genetic covariances due to pleiotropic mutations are obtained. Patterns of genetic covariance between characters and their evolution are discussed with reference to data on polygenic mutation, chromosomal organization and morphological integration.     

Landscape dynamics and evolution of colonizer syndromes: interactions between reproductive effortand dispersal in a metapopulation

The evolutionary consequences of changes in landscape dynamics for the evolution of life history syndromes are studied using a metapopulation model. We consider in turn the long-term effects of a change in the local disturbance rate, in the maximal local population persistence, in habitat productivity, and in habitat fragmentation. We examine the consequences of selective interactions between dispersal and reproductive effort by comparing the outcome of joint evolution to a situation where the species has lost the potential to evolve either its reproductive effort or its dispersal rate. We relax the classical assumption that any occupied site in the metapopulation reaches its carrying capacity immediately after recolonization. Our main conclusions are the following: (1) genetic diversity modifies the range of landscape parameters for which the metapopulation is viable, but it alters very little the qualitative evolutionary trends observed for each trait within this range. Although they are both part of a competition/colonization axis, reproductive effort and dispersal are not substitutable traits: their evolution reflects more directly the change in the landscape dynamics, than a selective interaction among them. (2) no general syndrome of covariation between reproductive effort and dispersal can be predicted: the pattern of association between the two traits depends on the type of change in landscape dynamics and on the saturation level. We review empirical evidence on colonizer syndromes and suggest lines for further empirical work. This revised version was published online in July 2006 with corrections to the Cover Date.     

Patterns of morphological integration in the appendicular skeleton of mammalian carnivores

We investigated patterns of evolutionary integration in the appendicular skeleton of mammalian carnivores. The findings are discussed in relation to performance selection in terms of organismal function as a potential mechanism underlying integration. Interspecific shape covariation was quantified by two‐block partial least‐squares (2B‐PLS) analysis of 3D landmark data within a phylogenetic context. Specifically, we compared pairs of anatomically connected bones (within‐limbs) and pairs of both serially homologous and functional equivalent bones (between‐limbs). The statistical results of all the comparisons suggest that the carnivoran appendicular skeleton is highly integrated. Strikingly, the main shape covariation relates to bone robustness in all cases. A bootstrap test was used to compare the degree of integration between specialized cursorial taxa (i.e., those whose forelimbs are primarily involved in locomotion) and noncursorial species (i.e., those whose forelimbs are involved in more functions than their hindlimb) showed that cursors have a more integrated appendicular skeleton than noncursors. The findings demonstrate that natural selection can influence the pattern and degree of morphological integration by increasing the degree of bone shape covariation in parallel to ecological specialization.     

Brain evolution and development: adaptation,allometry and constraint

Phenotypic traits are products of two processes: evolution and development. But how do these processes combine to produce integrated phenotypes? Comparative studies identify consistent patterns of covariation, or allometries, between brain and body size, and between brain components, indicating the presence of significant constraints limiting independent evolution of separate parts. These constraints are poorly understood, but in principle could be either developmental or functional. The developmental constraints hypothesis suggests that individual components (brain and body size, or individual brain components) tend to evolve together because natural selection operates on relatively simple developmental mechanisms that affect the growth of all parts in a concerted manner. The functional constraints hypothesis suggests that correlated change reflects the action of selection on distributed functional systems connecting the different sub-components, predicting more complex patterns of mosaic change at the level of the functional systems and more complex genetic and developmental mechanisms. These hypotheses are not mutually exclusive but make different predictions. We review recent genetic and neurodevelopmental evidence, concluding that functional rather than developmental constraints are the main cause of the observed patterns.     

Protein biophysics explains why highly abundant proteins evolve slowly

The consistent observation across all kingdoms of life that highly abundant proteins evolve slowly demonstrates that cellular abundance is a key determinant of protein evolutionary rate. However, other empirical findings, such as the broad distribution of evolutionary rates, suggest that additional variables determine the rate of protein evolution. Here, we report that under the global selection against the cytotoxic effects of misfolded proteins, folding stability (ΔG), simultaneous with abundance, is a causal variable of evolutionary rate. Using both theoretical analysis and multiscale simulations, we demonstrate that the anticorrelation between the premutation ΔG and the arising mutational effect (ΔΔG), purely biophysical in origin, is a necessary requirement for abundance-evolutionary rate covariation. Additionally, we predict and demonstrate in bacteria that the strength of abundance-evolutionary rate correlation depends on the divergence time separating reference genomes. Altogether, these results highlight the intrinsic role of protein biophysics in the emerging universal patterns of molecular evolution.     

Rate of evolutionary change in cranial morphology of the marsupial genus Monodelphis is constrained by the availability of additive genetic variation

We tested the hypothesis that the rate of marsupial cranial evolution is dependent on the distribution of genetic variation in multivariate space. To do so, we carried out a genetic analysis of cranial morphological variation in laboratory strains of Monodelphis domestica and used estimates of genetic covariation to analyse the morphological diversification of the Monodelphis brevicaudata species group. We found that within‐species genetic variation is concentrated in only a few axes of the morphospace and that this strong genetic covariation influenced the rate of morphological diversification of the brevicaudata group, with between‐species divergence occurring fastest when occurring along the genetic line of least resistance. Accounting for the geometric distribution of genetic variation also increased our ability to detect the selective regimen underlying species diversification, with several instances of selection only being detected when genetic covariances were taken into account. Therefore, this work directly links patterns of genetic covariation among traits to macroevolutionary patterns of morphological divergence. Our findings also suggest that the limited distribution of Monodelphis species in morphospace is the result of a complex interplay between the limited dimensionality of available genetic variation and strong stabilizing selection along two major axes of genetic variation.     

Constraints on geographic variation in fiddler crabs (Ocypodidae: Uca) from the western Atlantic

A key question in evolutionary biology is how intraspecific variation biases the evolution of a population and its divergence from other populations. Such constraints potentially limit the extent to which populations respond to selection, but may endure long enough to have macroevolutionary consequences. Previous studies have focused on the association between covariation patterns and divergence among isolated populations. Few have focused on geographic variation among semi‐connected populations, however, even though this may be indicative of early selective pressures that could lead to long‐term divergence and speciation. Here, we test whether covariation in the shape of the carapace of fiddler crabs (genus Uca Leach, 1814) is important for structuring geographic variation. We find that morphological divergence among populations is associated with evolvability in the direction of divergence in only a few species. The shape of the ancestral covariation matrix in these species differs from other species in having notably more variation concentrated along fewer directions (i.e. higher eccentricity). For most species, there is some evidence that covariation has constrained the range of directions into which populations have diverged but not the degree of divergence. These results suggest that even though fiddler crab populations have diverged morphologically in directions predicted by covariation, constraints on the extent to which divergence has occurred may only be manifested in species where variation patterns are eccentric enough to limit populations’ ability to respond effectively in many directions.     

The prediction of adaptive evolution: empirical application of the secondary theorem of selection and comparison to the breeder's equation

Adaptive evolution occurs when fitness covaries with genetic merit for a trait (or traits). The breeder's equation (BE), in both its univariate and multivariate forms, allows us to predict this process by combining estimates of selection on phenotype with estimates of genetic (co)variation. However, predictions are only valid if all factors causal for trait-fitness covariance are measured. Although this requirement will rarely (if ever) be met in practice, it can be avoided by applying Robertson's secondary theorem of selection (STS). The STS predicts evolution by directly estimating the genetic basis of trait-fitness covariation without any explicit model of selection. Here we apply the BE and STS to four morphological traits measured in Soay sheep (Ovis aries) from St. Kilda. Despite apparently positive selection on heritable size traits, sheep are not getting larger. However, although the BE predicts increasing size, the STS does not, which is a discrepancy that suggests unmeasured factors are upwardly biasing our estimates of selection on phenotype. We suggest this is likely to be a general issue, and that wider application of the STS could offer at least a partial resolution to the common discrepancy between naive expectations and observed trait dynamics in natural populations.     

Clonal Interference in the Evolution of Influenza

The seasonal influenza A virus undergoes rapid evolution to escape human immune response. Adaptive changes occur primarily in antigenic epitopes, the antibody-binding domains of the viral hemagglutinin. This process involves recurrent selective sweeps, in which clusters of simultaneous nucleotide fixations in the hemagglutinin coding sequence are observed about every 4 years. Here, we show that influenza A (H3N2) evolves by strong clonal interference. This mode of evolution is a red queen race between viral strains with different beneficial mutations. Clonal interference explains and quantifies the observed sweep pattern: we find an average of at least one strongly beneficial amino acid substitution per year, and a given selective sweep has three to four driving mutations on average. The inference of selection and clonal interference is based on frequency time series of single-nucleotide polymorphisms, which are obtained from a sample of influenza genome sequences over 39 years. Our results imply that mode and speed of influenza evolution are governed not only by positive selection within, but also by background selection outside antigenic epitopes: immune adaptation and conservation of other viral functions interfere with each other. Hence, adapting viral proteins are predicted to be particularly brittle. We conclude that a quantitative understanding of influenza’s evolutionary and epidemiological dynamics must be based on all genomic domains and functions coupled by clonal interference.     

Relaxation of herbivore‐mediated selection drives the evolution of genetic covariances between plant competitive and defense traits

Insect herbivores are important mediators of selection on traits that impact plant defense against herbivory and competitive ability. Although recent experiments demonstrate a central role for herbivory in driving rapid evolution of defense and competition‐mediating traits, whether and how herbivory shapes heritable variation in these traits remains poorly understood. Here, we evaluate the structure and evolutionary stability of the G matrix for plant metabolites that are involved in defense and allelopathy in the tall goldenrod, Solidago altissima. We show that G has evolutionarily diverged between experimentally replicated populations that evolved in the presence versus the absence of ambient herbivory, providing direct evidence for the evolution of G by natural selection. Specifically, evolution in an herbivore‐free habitat altered the orientation of G , revealing a negative genetic covariation between defense‐ and competition‐related metabolites that is typically masked in herbivore‐exposed populations. Our results may be explained by predictions of classical quantitative genetic theory, as well as the theory of acquisition‐allocation trade‐offs. The study provides compelling evidence that herbivory drives the evolution of plant genetic architecture.