The predictive power of genetic variation.

New analyses show that trait variability links evolution across vastly different timescales.

Demographic feedbacks during evolutionary rescue can slow or speed adaptive evolution.

Populations declining toward extinction can persist via genetic adaptation in a process called evolutionary rescue. Predicting evolutionary rescue has applications ranging from conservation biology to medicine, but requires understanding and integrating the multiple effects of a stressful environmental change on population processes. Here we derive a simple expression for how generation time, a key determinant of the rate of evolution, varies with population size during evolutionary rescue. Change in generation time is quantitatively predicted by comparing how intraspecific competition and the source of maladaptation each affect the rates of births and deaths in the population. Depending on the difference between two parameters quantifying these effects, the model predicts that populations may experience substantial changes in their rate of adaptation in both positive and negative directions, or adapt consistently despite severe stress. These predictions were then tested by comparison to the results of individual-based simulations of evolutionary rescue, which validated that the tolerable rate of environmental change varied considerably as described by analytical results. We discuss how these results inform efforts to understand wildlife disease and adaptation to climate change, evolution in managed populations and treatment resistance in pathogens.

Conservation and Convergence of Genetic Architecture in the Adaptive Radiation of Anolis Lizards.

AbstractThe G matrix, which quantifies the genetic architecture of traits, is often viewed as an evolutionary constraint. However, G can evolve in response to selection and may also be viewed as a product of adaptive evolution. Convergent evolution of G in similar environments would suggest that G evolves adaptively, but it is difficult to disentangle such effects from phylogeny. Here, we use the adaptive radiation of Anolis lizards to ask whether convergence of G accompanies the repeated evolution of habitat specialists, or ecomorphs, across the Greater Antilles. We measured G in seven species representing three ecomorphs (trunk-crown, trunk-ground, and grass-bush). We found that the overall structure of G does not converge. Instead, the structure of G is well conserved and displays a phylogenetic signal consistent with Brownian motion. However, several elements of G showed signatures of convergence, indicating that some aspects of genetic architecture have been shaped by selection. Most notably, genetic correlations between limb traits and body traits were weaker in long-legged trunk-ground species, suggesting effects of recurrent selection on limb length. Our results demonstrate that common selection pressures may have subtle but consistent effects on the evolution of G, even as its overall structure remains conserved.

The road not taken: Evolution of tetrodotoxin resistance in the Sierra garter snake (Thamnophis couchii) by a path less travelled.

The repeated evolution of tetrodotoxin (TTX) resistance provides a model for testing hypotheses about the mechanisms of convergent evolution. This poison is broadly employed as a potent antipredator defence, blocking voltage-gated sodium channels (Nav ) in muscles and nerves, paralysing and sometimes killing predators. Resistance in taxa bearing this neurotoxin and a few predators appears to come from convergent replacements in specific Nav residues that interact with TTX. This stereotyped genetic response suggests molecular and phenotypic evolution may be constrained and predictable. Here, we investigate the extent of mechanistic convergence in garter snakes (Thamnophis) that prey on TTX-bearing newts (Taricha) by examining the physiological and genetic basis of TTX resistance in the Sierra garter snake (Th. couchii). We characterize variation in this predatory adaptation across populations at several biological scales: whole-animal TTX resistance; skeletal muscle resistance; functional genetic variation in three Nav encoding loci; and levels of gene expression for one of these loci. We found Th. couchii possess extensive geographical variation in resistance at the whole-animal and skeletal muscle levels. As in other Thamnophis, resistance at both levels is highly correlated, suggesting convergence across the biological levels linking organism to organ. However, Th. couchii shows no functional variation in Nav loci among populations or difference in candidate gene expression. Local variation in TTX resistance in Th. couchii cannot be explained by the same relationship between genotype and phenotype seen in other taxa. Thus, historical contingencies may lead different species of Thamnophis down alternative routes to local adaptation.

A Synthesis of Game Theory and Quantitative Genetic Models of Social Evolution.

Two popular approaches for modeling social evolution, evolutionary game theory and quantitative genetics, ask complementary questions but are rarely integrated. Game theory focuses on evolutionary outcomes, with models solving for evolutionarily stable equilibria, whereas quantitative genetics provides insight into evolutionary processes, with models predicting short-term responses to selection. Here we draw parallels between evolutionary game theory and interacting phenotypes theory, which is a quantitative genetic framework for understanding social evolution. First, we show how any evolutionary game may be translated into two quantitative genetic selection gradients, nonsocial and social selection, which may be used to predict evolutionary change from a single round of the game. We show that synergistic fitness effects may alter predicted selection gradients, causing changes in magnitude and sign as the population mean evolves. Second, we show how evolutionary games involving plastic behavioral responses to partners can be modeled using indirect genetic effects, which describe how trait expression changes in response to genes in the social environment. We demonstrate that repeated social interactions in models of reciprocity generate indirect effects and conversely, that estimates of parameters from indirect genetic effect models may be used to predict the evolution of reciprocity. We argue that a pluralistic view incorporating both theoretical approaches will benefit empiricists and theorists studying social evolution. We advocate the measurement of social selection and indirect genetic effects in natural populations to test the predictions from game theory and, in turn, the use of game theory models to aid in the interpretation of quantitative genetic estimates.

Interacting phenotypes and the coevolutionary process: Interspecific indirect genetic effects alter coevolutionary dynamics.

Coevolution occurs when species interact to influence one another's fitness, resulting in reciprocal evolutionary change. In many coevolving lineages, trait expression in one species is modified by the genotypes and phenotypes of the other, forming feedback loops reminiscent of models of intraspecific social evolution. Here, we adapt the theory of within-species social evolution, characterized by indirect genetic effects and social selection imposed by interacting individuals, to the case of interspecific interactions. In a trait-based model, we derive general expressions for multivariate evolutionary change in two species and the expected between-species covariance in evolutionary change when selection varies across space. We show that reciprocal interspecific indirect genetic effects can dominate the coevolutionary process and drive patterns of correlated evolution beyond what is expected from direct selection alone. In extreme cases, interspecific indirect genetic effects can lead to coevolution when selection does not covary between species or even when one species lacks genetic variance. Moreover, our model indicates that interspecific indirect genetic effects may interact in complex ways with cross-species selection to determine the course of coevolution. Importantly, our model makes empirically testable predictions for how different forms of reciprocal interactions contribute to the coevolutionary process.

Social Selection and the Evolution of Maladaptation.

Evolution by natural selection is often viewed as a process that inevitably leads to adaptation or an increase in population fitness over time. However, maladaptation, an evolved decrease in fitness, may also occur in response to natural selection under some conditions. Social selection, which arises from the effects of social partners on fitness, has been identified as a potential cause of maladaptation, but we lack a general rule identifying when social selection should lead to a decrease in population mean fitness. Here we use a quantitative genetic model to develop such a rule. We show that maladaptation is most likely to occur when social selection is strong relative to nonsocial selection and acts in an opposing direction. In this scenario, the evolution of traits that impose fitness costs on others may outweigh evolved gains in fitness for the individual, leading to a net decrease in population mean fitness. Furthermore, we find that maladaptation may also sometimes occur when phenotypes of interacting individuals negatively covary. We outline the biological situations where maladaptation in response to social selection can be expected, provide both quantitative genetic and phenotypic versions of our derived result, and suggest what empirical work would be needed to test it. We also consider the effect of social selection on inclusive fitness and support previous work showing that inclusive fitness cannot suffer an evolutionary decrease. Taken together, our results show that social selection may decrease population mean fitness when it opposes individual-level selection, even as inclusive fitness increases.

Runaway evolution from male-male competition.

Wondrously elaborate weapons and displays that appear to be counter to ecological optima are widespread features of male contests for mates across the animal kingdom. To understand how such diverse traits evolve, here we develop a quantitative genetic model of sexual selection for a male signaling trait that mediates aggression in male-male contests and show that an honest indicator of aggression can generate selection on itself by altering the social environment. This can cause selection to accelerate as the trait is elaborated, leading to runaway evolution. Thus, an evolving source of selection provided by the social environment is the fundamental unifying feature of runaway sexual selection driven by either male-male competition or female mate choice. However, a key difference is that runaway driven by male-male competition requires signal honesty. Our model identifies simple conditions that provide clear, testable predictions for empirical studies using standard quantitative genetic methods.

Assessing age, breeding stage, and mating activity as drivers of variation in the reproductive microbiome of female tree swallows.

Sexually transmitted microbes are hypothesized to influence the evolution of reproductive strategies. Though frequently discussed in this context, our understanding of the reproductive microbiome is quite nascent. Indeed, testing this hypothesis first requires establishing a baseline understanding of the temporal dynamics of the reproductive microbiome and of how individual variation in reproductive behavior and age influence the assembly and maintenance of the reproductive microbiome as a whole. Here, we ask how mating activity, breeding stage, and age influence the reproductive microbiome. We use observational and experimental approaches to explain variation in the cloacal microbiome of free-living, female tree swallows (Tachycineta bicolor). Using microsatellite-based parentage analyses, we determined the number of sires per brood (a proxy for female mating activity). We experimentally increased female sexual activity by administering exogenous 17ß-estradiol. Lastly, we used bacterial 16S rRNA amplicon sequencing to characterize the cloacal microbiome. Neither the number of sires per brood nor the increased sexual activity of females significantly influenced female cloacal microbiome richness or community structure. Female age, however, was positively correlated with cloacal microbiome richness and influenced overall community structure. A hypothesis to explain these patterns is that the effect of sexual activity and the number of mates on variation in the cloacal microbiome manifests over an individual's lifetime. Additionally, we found that cloacal microbiome alpha diversity (Shannon Index, Faith's phylogenetic distance) decreased and community structure shifted between breeding stages. This is one of few studies to document within-individual changes and age-related differences in the cloacal microbiome across successive breeding stages. More broadly, our results contribute to our understanding of the role that host life history and behavior play in shaping the cloacal microbiomes of wild birds.

Hormonal pleiotropy structures genetic covariance.

Quantitative genetic theory proposes that phenotypic evolution is shaped by G, the matrix of genetic variances and covariances among traits. In species with separate sexes, the evolution of sexual dimorphism is also shaped by B, the matrix of between-sex genetic variances and covariances. Despite considerable focus on estimating these matrices, their underlying biological mechanisms are largely speculative. We experimentally tested the hypothesis that G and B are structured by hormonal pleiotropy, which occurs when one hormone influences multiple phenotypes. Using juvenile brown anole lizards (Anolis sagrei) bred in a paternal half-sibling design, we elevated the steroid hormone testosterone with slow-release implants while administering empty implants to siblings as a control. We quantified the effects of this manipulation on the genetic architecture of a suite of sexually dimorphic traits, including body size (males are larger than females) and the area, hue, saturation, and brightness of the dewlap (a colorful ornament that is larger in males than in females). Testosterone masculinized females by increasing body size and dewlap area, hue, and saturation, while reducing dewlap brightness. Control females and males differed significantly in G, but treatment of females with testosterone rendered G statistically indistinguishable from males. Whereas B was characterized by low between-sex genetic correlations when estimated between control females and males, these same correlations increased significantly when estimated between testosterone females and either control or testosterone males. The full G matrix (including B) for testosterone females and either control or testosterone males was significantly less permissive of sexually dimorphic evolution than was G estimated between control females and males, suggesting that natural sex differences in testosterone help decouple genetic variance between the sexes. Our results confirm that hormonal pleiotropy structures genetic covariance, implying that hormones play an important yet overlooked role in mediating evolutionary responses to selection.

Gene Conversion Facilitates the Adaptive Evolution of Self-Resistance in Highly Toxic Newts.

Reconstructing the histories of complex adaptations and identifying the evolutionary mechanisms underlying their origins are two of the primary goals of evolutionary biology. Taricha newts, which contain high concentrations of the deadly toxin tetrodotoxin (TTX) as an antipredator defense, have evolved resistance to self-intoxication, which is a complex adaptation requiring changes in six paralogs of the voltage-gated sodium channel (Nav) gene family, the physiological target of TTX. Here, we reconstruct the origins of TTX self-resistance by sequencing the entire Nav gene family in newts and related salamanders. We show that moderate TTX resistance evolved early in the salamander lineage in three of the six Nav paralogs, preceding the proposed appearance of tetrodotoxic newts by ∼100 My. TTX-bearing newts possess additional unique substitutions across the entire Nav gene family that provide physiological TTX resistance. These substitutions coincide with signatures of positive selection and relaxed purifying selection, as well as gene conversion events, that together likely facilitated their evolution. We also identify a novel exon duplication within Nav1.4 encoding an expressed TTX-binding site. Two resistance-conferring changes within newts appear to have spread via nonallelic gene conversion: in one case, one codon was copied between paralogs, and in the second, multiple substitutions were homogenized between the duplicate exons of Nav1.4. Our results demonstrate that gene conversion can accelerate the coordinated evolution of gene families in response to a common selection pressure.

Sex linkage of the skeletal muscle sodium channel gene (SCN4A) explains apparent deviations from Hardy-Weinberg equilibrium of tetrodotoxin-resistance alleles in garter snakes (Thamnophis sirtalis).

The arms race between tetrodotoxin-bearing Pacific newts (Taricha) and their garter snake predators (Thamnophis) in western North America has become a classic example of coevolution, shedding light on predator-prey dynamics, the molecular basis of adaptation, and patterns of convergent evolution. Newts are defended by tetrodotoxin (TTX), a neurotoxin that binds to voltage-gated sodium channels (Nav proteins), arresting electrical activity in nerves and muscles and paralyzing would-be predators. However, populations of the common garter snake (T. sirtalis) have overcome this defense, largely through polymorphism at the locus SCN4A, which renders the encoded protein (Nav1.4) less vulnerable to TTX. Previous work suggests that SCN4A commonly shows extreme deviations from Hardy-Weinberg equilibrium (HWE) in these populations, which has been interpreted as the result of intense selection imposed by newts. Here we show that much of this apparent deviation can be attributed to sex linkage of SCN4A. Using genomic data and quantitative PCR, we show that SCN4A is on the Z chromosome in Thamnophis and other advanced snakes. Taking Z-linkage into account, we find that most apparent deviations from HWE can be explained by female hemizygosity rather than low heterozygosity. Sex linkage can affect mutation rates, selection, and drift, and our results suggest that Z-linkage of SCN4A may make significant contributions to the overall dynamics of the coevolutionary arms race between newts and snakes.

Sex-Specific Selection and the Evolution of Between-Sex Genetic Covariance.

Because the sexes share a genome, traits expressed in males are usually genetically correlated with the same traits expressed in females. On short timescales, between-sex genetic correlations (rmf) for shared traits may constrain the evolution of sexual dimorphism by preventing males and females from responding independently to sex-specific selection. However, over longer timescales, rmf may evolve, thereby facilitating the evolution of dimorphism. Although it has been suggested that sexually antagonistic selection may reduce rmf, we lack a general theory for the evolution of rmf and its multivariate analog, the between-sex genetic covariance matrix (B). Here, we derive a simple analytical model for the within-generation change in B due to sex-specific directional selection. We present a single-trait example demonstrating that sex-specific directional selection may either increase or decrease between-sex genetic covariance, depending on the relative strength of selection in each sex and on the current value of rmf. Although sexually antagonistic selection can reduce between-sex covariance, it will only do so when selection is much stronger in one sex than in the other. Counterintuitively, sexually antagonistic selection that is equal in strength in the 2 sexes will maintain positive between-sex covariance. Selection acting in the same direction on both sexes is predicted to reduce between-sex covariance in many cases. We illustrate our model numerically using empirical measures of sex-specific selection and between-sex genetic covariance from 2 populations of sexually dimorphic brown anole lizards (Anolis sagrei) and discuss its importance for understanding the resolution of intralocus sexual conflict.

Adaptive radiation along a deeply conserved genetic line of least resistance in Anolis lizards.

On microevolutionary timescales, adaptive evolution depends upon both natural selection and the underlying genetic architecture of traits under selection, which may constrain evolutionary outcomes. Whether such genetic constraints shape phenotypic diversity over macroevolutionary timescales is more controversial, however. One key prediction is that genetic constraints should bias the early stages of species divergence along "genetic lines of least resistance" defined by the genetic (co)variance matrix, G. This bias is expected to erode over time as species means and G matrices diverge, allowing phenotypes to evolve away from the major axis of variation. We tested for evidence of this signal in West Indian Anolis lizards, an iconic example of adaptive radiation. We found that the major axis of morphological evolution was well aligned with a major axis of genetic variance shared by all species despite separation times of 20-40 million years, suggesting that divergence occurred along a conserved genetic line of least resistance. Further, this signal persisted even as G itself evolved, apparently because the largest evolutionary changes in G were themselves aligned with the line of genetic least resistance. Our results demonstrate that the signature of genetic constraint may persist over much longer timescales than previously appreciated, even in the presence of evolving genetic architecture. This pattern may have arisen either because pervasive constraints have biased the course of adaptive evolution or because the G matrix itself has been shaped by selection to conform to the adaptive landscape.

Molecular Adaptations for Sensing and Securing Prey and Insight into Amniote Genome Diversity from the Garter Snake Genome.

Colubridae represents the most phenotypically diverse and speciose family of snakes, yet no well-assembled and annotated genome exists for this lineage. Here, we report and analyze the genome of the garter snake, Thamnophis sirtalis, a colubrid snake that is an important model species for research in evolutionary biology, physiology, genomics, behavior, and the evolution of toxin resistance. Using the garter snake genome, we show how snakes have evolved numerous adaptations for sensing and securing prey, and identify features of snake genome structure that provide insight into the evolution of amniote genomes. Analyses of the garter snake and other squamate reptile genomes highlight shifts in repeat element abundance and expansion within snakes, uncover evidence of genes under positive selection, and provide revised neutral substitution rate estimates for squamates. Our identification of Z and W sex chromosome-specific scaffolds provides evidence for multiple origins of sex chromosome systems in snakes and demonstrates the value of this genome for studying sex chromosome evolution. Analysis of gene duplication and loss in visual and olfactory gene families supports a dim-light ancestral condition in snakes and indicates that olfactory receptor repertoires underwent an expansion early in snake evolution. Additionally, we provide some of the first links between secreted venom proteins, the genes that encode them, and their evolutionary origins in a rear-fanged colubrid snake, together with new genomic insight into the coevolutionary arms race between garter snakes and highly toxic newt prey that led to toxin resistance in garter snakes.

Thermal physiology and thermoregulatory behaviour exhibit low heritability despite genetic divergence between lizard populations.

Ectothermic species are particularly sensitive to changes in temperature and may adapt to changes in thermal environments through evolutionary shifts in thermal physiology or thermoregulatory behaviour. Nevertheless, the heritability of thermal traits, which sets a limit on evolutionary potential, remains largely unexplored. In this study, we captured brown anole lizards (Anolis sagrei) from two populations that occur in contrasting thermal environments. We raised offspring from these populations in a laboratory common garden and compared the shape of their thermal performance curves to test for genetic divergence in thermal physiology. Thermal performance curves differed between populations in a common garden in ways partially consistent with divergent patterns of natural selection experienced by the source populations, implying that they had evolved in response to selection. Next, we estimated the heritability of thermal performance curves and of several traits related to thermoregulatory behaviour. We did not detect significant heritability in most components of the thermal performance curve or in several aspects of thermoregulatory behaviour, suggesting that contemporary selection is unlikely to result in rapid evolution. Our results indicate that the response to selection may be slow in the brown anole and that evolutionary change is unlikely to keep pace with current rates of environmental change.

Social structure modulates the evolutionary consequences of social plasticity: A social network perspective on interacting phenotypes.

Organisms express phenotypic plasticity during social interactions. Interacting phenotype theory has explored the consequences of social plasticity for evolution, but it is unclear how this theory applies to complex social structures. We adapt interacting phenotype models to general social structures to explore how the number of social connections between individuals and preference for phenotypically similar social partners affect phenotypic variation and evolution. We derive an analytical model that ignores phenotypic feedback and use simulations to test the predictions of this model. We find that adapting previous models to more general social structures does not alter their general conclusions but generates insights into the effect of social plasticity and social structure on the maintenance of phenotypic variation and evolution. Contribution of indirect genetic effects to phenotypic variance is highest when interactions occur at intermediate densities and decrease at higher densities, when individuals approach interacting with all group members, homogenizing the social environment across individuals. However, evolutionary response to selection tends to increase at greater network densities as the effects of an individual's genes are amplified through increasing effects on other group members. Preferential associations among similar individuals (homophily) increase both phenotypic variance within groups and evolutionary response to selection. Our results represent a first step in relating social network structure to the expression of social plasticity and evolutionary responses to selection.

Hormonally Mediated Increases in Sex-Biased Gene Expression Accompany the Breakdown of Between-Sex Genetic Correlations in a Sexually Dimorphic Lizard.

The evolution of sexual dimorphism is predicted to occur through reductions in between-sex genetic correlations (rmf) for shared traits, but the physiological and genetic mechanisms that facilitate these reductions remain largely speculative. Here, we use a paternal half-sibling breeding design in captive brown anole lizards (Anolis sagrei) to show that the development of sexual size dimorphism is mirrored by the ontogenetic breakdown of rmf for body size and growth rate. Using transcriptome data from the liver (which integrates growth and metabolism), we show that sex-biased gene expression also increases dramatically between ontogenetic stages bracketing this breakdown of rmf. Ontogenetic increases in sex-biased expression are particularly evident for genes involved in growth, metabolism, and cell proliferation, suggesting that they contribute to both the development of sexual dimorphism and the breakdown of rmf. Mechanistically, we show that treatment of females with testosterone stimulates the expression of male-biased genes while inhibiting the expression of female-biased genes, thereby inducing male-like phenotypes at both organismal and transcriptomic levels. Collectively, our results suggest that sex-specific modifiers such as testosterone can orchestrate sex-biased gene expression to facilitate the phenotypic development of sexual dimorphism while simultaneously reducing genetic correlations that would otherwise constrain the independent evolution of the sexes.

Hormones as Mediators of Phenotypic and Genetic Integration: an Evolutionary Genetics Approach.

Evolutionary endocrinology represents a synthesis between comparative endocrinology and evolutionary genetics. This synthesis can be viewed through the breeder's equation, a cornerstone of quantitative genetics that, in its univariate form, states that a population's evolutionary response is the product of the heritability of a trait and selection on that trait (R = h(2)S). Under this framework, evolutionary endocrinologists have begun to quantify the heritability of, and the strength of selection on, a variety of hormonal phenotypes. With specific reference to our work on testosterone and corticosterone in birds and lizards, we review these studies while emphasizing the challenges of applying this framework to hormonal phenotypes that are inherently plastic and mediate adaptive responses to environmental variation. Next, we consider the untapped potential of evolutionary endocrinology as a framework for exploring multivariate versions of the breeder's equation, with emphasis on the role of hormones in structuring phenotypic and genetic correlations. As an extension of the familiar concepts of phenotypic integration and hormonal pleiotropy, we illustrate how the hormonal milieu of an individual acts as a local environment for the expression of genes and phenotypes, thereby influencing the quantitative genetic architecture of multivariate phenotypes. We emphasize that hormones are more than mechanistic links in the translation of genotype to phenotype: by virtue of their pleiotropic effects on gene expression, hormones structure the underlying genetic variances and covariances that determine a population's evolutionary response to selection.