Evolutionary quantitative genetics of nonlinear developmental systems

In quantitative genetics, the effects of developmental relationships among traits on microevolution are generally represented by the contribution of pleiotropy to additive genetic covariances. Pleiotropic additive genetic covariances arise only from the average effects of alleles on multiple traits, and therefore the evolutionary importance of nonlinearities in development is generally neglected in quantitative genetic views on evolution. However, nonlinearities in relationships among traits at the level of whole organisms are undeniably important to biology in general, and therefore critical to understanding evolution. I outline a system for characterizing key quantitative parameters in nonlinear developmental systems, which yields expressions for quantities such as trait means and phenotypic and genetic covariance matrices. I then develop a system for quantitative prediction of evolution in nonlinear developmental systems. I apply the system to generating a new hypothesis for why direct stabilizing selection is rarely observed. Other uses will include separation of purely correlative from direct and indirect causal effects in studying mechanisms of selection, generation of predictions of medium‐term evolutionary trajectories rather than immediate predictions of evolutionary change over single generation time‐steps, and the development of efficient and biologically motivated models for separating additive from epistatic genetic variances and covariances.     

The constancy of the G matrix through species divergence and the effects of quantitative genetic constraints on phenotypic evolution: a case study in crickets

Long-term phenotypic evolution can be modeled using the response-to-selection equation of quantitative genetics, which incorporates information about genetic constraints (the G matrix). However, little is known about the evolution of G and about its long-term importance in constraining phenotypic evolution. We first investigated the degree of conservation of the G matrix across three species of crickets and qualitatively compared the pattern of variation of G to the phylogeny of the group. Second, we investigated the effect of G on phenotypic evolution by comparing the direction of greatest quantitative genetic variation within species (g(max)) to the direction of phenotypic divergence between species (Delta(z)). Each species, Gryllus veletis, G. firmus, and G. pennsylvanicus, was reared in the laboratory using a full-sib breeding design to extract quantitative genetic information. Five morphological traits related to size were measured. G matrices were compared using three statistical approaches: the T method, the Flury hierarchy, and the MANOVA method. Results revealed that the differences between matrices were small and mostly caused by differences in the magnitude of the genetic variation, not by differences in principal component structure. This suggested that the G matrix structure of this group of species was preserved, despite significant phenotypic divergence across species. The small observed differences in G matrices across species were qualitatively consistent with genetic distances, whereas ecological information did not provide a good prediction of G matrix variation. The comparison of g(max) and Delta(z) revealed that the angle between these two vectors was small in two of three species comparisons, whereas the larger angle corresponding to the third species comparison was caused in large part by one of the five traits. This suggests that multivariate phenotypic divergence occurred mostly in a direction predicted by the direction of greatest genetic variation, although it was not possible to demonstrate the causal relationship from G to Delta(z). Overall, this study provided some support for the validity of the predictive power of quantitative genetics over evolutionary time scales.     

Developmental interactions and the constituents of quantitative variation

Development is the process by which genotypes are transformed into phenotypes. Consequently, development determines the relationship between allelic and phenotypic variation in a population and, therefore, the patterns of quantitative genetic variation and covariation of traits. Understanding the developmental basis of quantitative traits may lead to insights into the origin and evolution of quantitative genetic variation, the evolutionary fate of populations, and, more generally, the relationship between development and evolution. Herein, we assume a hierarchical, modular structure of trait development and consider how epigenetic interactions among modules during ontogeny affect patterns of phenotypic and genetic variation. We explore two developmental models, one in which the epigenetic interactions between modules result in additive effects on character expression and a second model in which these epigenetic interactions produce nonadditive effects. Using a phenotype landscape approach, we show how changes in the developmental processes underlying phenotypic expression can alter the magnitude and pattern of quantitative genetic variation. Additive epigenetic effects influence genetic variances and covariances, but allow trait means to evolve independently of the genetic variances and covariances, so that phenotypic evolution can proceed without changing the genetic covariance structure that determines future evolutionary response. Nonadditive epigenetic effects, however, can lead to evolution of genetic variances and covariances as the mean phenotype evolves. Our model suggests that an understanding of multivariate evolution can be considerably enriched by knowledge of the mechanistic basis of character development.     

A multiple peak adaptive landscape based on feeding strategies and roosting ecology shaped the evolution of cranial covariance structure and morphological differentiation in phyllostomid bats

We explored the evolution of morphological integration in the most noteworthy example of adaptive radiation in mammals, the New World leaf‐nosed bats, using a massive dataset and by combining phylogenetic comparative methods and quantitative genetic approaches. We demonstrated that the phenotypic covariance structure remained conserved on a broader phylogenetic scale but also showed a substantial divergence between interclade comparisons. Most of the phylogenetic structure in the integration space can be explained by splits at the beginning of the diversification of major clades. Our results provide evidence for a multiple peak adaptive landscape in the evolution of cranial covariance structure and morphological differentiation, based upon diet and roosting ecology. In this scenario, the successful radiation of phyllostomid bats was triggered by the diversification of dietary and roosting strategies, and the invasion of these new adaptive zones lead to changes in phenotypic covariance structure and average morphology. Our results suggest that intense natural selection preceded the invasion of these new adaptive zones and played a fundamental role in shaping cranial covariance structure and morphological differentiation in this hyperdiverse clade of mammals. Finally, our study demonstrates the power of combining comparative methods and quantitative genetic approaches when investigating the evolution of complex morphologies.     

Evolution of phenotypic plasticity: where are we going now?

The study of phenotypic plasticity has progressed significantly over the past few decades. We have moved from variation for plasticity being considered as a nuisance in evolutionary studies to it being the primary target of investigations that use an array of methods, including quantitative and molecular genetics, as well as of several approaches that model the evolution of plastic responses. Here, I consider some of the major aspects of research on phenotypic plasticity, assessing where progress has been made and where additional effort is required. I suggest that some areas of research, such the study of the quantitative genetic underpinning of plasticity, have been either settled in broad outline or superseded by new approaches and questions. Other issues, such as the costs of plasticity are currently at the forefront of research in this field, and are likely to be areas of major future development.     

Testing the robustness of the likelihood-ratio test in a variance-component quantitative-trait loci-mapping procedure.

Detection of linkage to genes for quantitative traits remains a challenging task. Recently, variance components (VC) techniques have emerged as among the more powerful of available methods. As often implemented, such techniques require assumptions about the phenotypic distribution. Usually, multivariate normality is assumed. However, several factors may lead to markedly nonnormal phenotypic data, including (a) the presence of a major gene (not necessarily linked to the markers under study), (b) some types of gene x environment interaction, (c) use of a dichotomous phenotype (i.e., affected vs. unaffected), (d) nonnormality of the population within-genotype (residual) distribution, and (e) selective (extreme) sampling. Using simulation, we have investigated, for sib-pair studies, the robustness of the likelihood-ratio test for a VC quantitative-trait locus-detection procedure to violations of normality that are due to these factors. Results showed (a) that some types of nonnormality, such as leptokurtosis, produced type I error rates in excess of the nominal, or alpha, levels whereas others did not; and (b) that the degree of type I error-rate inflation appears to be directly related to the residual sibling correlation. Potential solutions to this problem are discussed. Investigators contemplating use of this VC procedure are encouraged to provide evidence that their trait data are normally distributed, to employ a procedure that allows for nonnormal data, or to consider implementation of permutation tests.     

Conceptual bases for quantifying the role of the environment on gene evolution: the participation of positive selection and neutral evolution

To demonstrate that a given change in the environment has contributed to the emergence of a given genotypic and phenotypic shift during the course of evolution, one should ask to what extent such shifts would have occurred without environmental change. Of course, such tests are rarely practical but phenotypic novelties can still be correlated to genomic shifts in response to environmental changes if enough information is available. We surveyed and re-evaluated the published data in order to estimate the role of environmental changes on the course of species and genomic evolution. Only a few published examples clearly demonstrate a causal link between a given environmental change and the fixation of a genomic variant resulting in functional modification (gain, loss or alteration of function). Many others suggested a link between a given phenotypic shift and a given environmental change but failed to identify the underlying genomic determinant(s) and/or the associated functional consequence(s). The proportion of genotypic and phenotypic variation that is fixed concomitantly with environmental changes is often considered adaptive and hence, the result of positive selection, even though alternative causes, such as genetic drift, are rarely investigated. Therefore, the second aim herein is to review evidence for the mechanisms leading to fixation.     

Evolution in response to social selection: the importance of interactive effects of traits on fitness

Social interactions have a powerful effect on the evolutionary process. Recent attempts to synthesize models of social selection with equations for indirect genetic effects (McGlothlin et al. 2010) provide a broad theoretical base from which to study selection and evolutionary response in the context of social interactions. However, this framework concludes that social selection will lead to evolution only if the traits carried by social partners are nonrandomly associated. I suggest this conclusion is incomplete, and that traits that do not covary between social partners can nevertheless lead to evolution via interactive effects on fitness. Such effects occur when there are functional interactions between traits, and as an example I use the interplay in water striders (Gerridae) between grasping appendages carried by males and spines by females. Functional interactive effects between traits can be incorporated into both the equations for social selection and the general model of social evolution proposed by McGlothlin et al. These expanded equations would accommodate adaptive coevolution in social interactions, integrate the quantitative genetic approach to social evolution with game theoretical approaches, and stimulate some new questions about the process of social evolution.     

Determining causality and consequence of expression quantitative trait loci

Expression quantitative trait loci (eQTLs) are currently the most abundant and systematically-surveyed class of functional consequence for genetic variation. Recent genetic studies of gene expression have identified thousands of eQTLs in diverse tissue types for the majority of human genes. Application of this large eQTL catalog provides an important resource for understanding the molecular basis of common genetic diseases. However, only now has both the availability of individuals with full genomes and corresponding advances in functional genomics provided the opportunity to dissect eQTLs to identify causal regulatory variants. Resolving the properties of such causal regulatory variants is improving understanding of the molecular mechanisms that influence traits and guiding the development of new genome-scale approaches to variant interpretation. In this review, we provide an overview of current computational and experimental methods for identifying causal regulatory variants and predicting their phenotypic consequences.     

Investigating Morphospace Occupation in Multi-Scale Ecological and Evolutionary Data Using Regression Tree: Case Studies and Perspectives

A key challenge in ecology and evolutionary biology is to explain the origin, structure and temporal patterns of phenotypic diversity. With regard to the potentially complex determinism of phenotypic differences, the issue should be comprehended in a general view, across multiple scales and an increasing number of phenomic studies investigate shape variation through large taxonomic, biogeographic or temporal scales. In this context, there is an ever-increasing need to develop new tools for a coherent understanding of morphospace occupation by disentangling and quantifying the main determinants of phenotypic changes. The present study briefly introduce the possibility to use multivariate regression tree technique to cope with morphological data, as embedded in a geometric morphometric framework. It emphasizes that hierarchical partitioning methods produce a hierarchy between causal variables that may help analyzing complexity in multi-scale ecological and evolutionary data. I therefore suggest that morphological studies would benefit from the combined use of the classical statistical models with rapidly emerging and diversifying methods of machine-learning. Doing so allows one to primary explore in an extensive exploratory manner the hierarchy of nested organisational levels underlying morphological variation, and then conduct hypothesis-driven analysis by focusing on a relevant scale or by investigating the appropriate model that reflects hypothesized nested influence of explanatory variables. The outlined approach may help investigating morphospace occupation in an explicitly hierarchical quantitative context.     

Phenotypic integration: studying the ecology and evolution of complex phenotypes

Phenotypic integration refers to the study of complex patterns of covariation among functionally related traits in a given organism. It has been investigated throughout the 20th century, but has only recently risen to the forefront of evolutionary ecological research. In this essay, I identify the reasons for this late flourishing of studies on integration, and discuss some of the major areas of current endeavour: the interplay of adaptation and constraints, the genetic and molecular bases of integration, the role of phenotypic plasticity, macroevolutionary studies of integration, and statistical and conceptual issues in the study of the evolution of complex phenotypes. I then conclude with a brief discussion of what I see as the major future directions of research on phenotypic integration and how they relate to our more general quest for the understanding of phenotypic evolution within the neo‐Darwinian framework. I suggest that studying integration provides a particularly stimulating and truly interdisciplinary convergence of researchers from fields as disparate as molecular genetics, developmental biology, evolutionary ecology, palaeontology and even philosophy of science.     

Origin of the fittest: link between emergent variation and evolutionary change as a critical question in evolutionary biology

In complex organisms, neutral evolution of genomic architecture, associated compensatory interactions in protein networks and emergent developmental processes can delineate the directions of evolutionary change, including the opportunity for natural selection. These effects are reflected in the evolution of developmental programmes that link genomic architecture with a corresponding functioning phenotype. Two recent findings call for closer examination of the rules by which these links are constructed. First is the realization that high dimensionality of genotypes and emergent properties of autonomous developmental processes (such as capacity for self-organization) result in the vast areas of fitness neutrality at both the phenotypic and genetic levels. Second is the ubiquity of context- and taxa-specific regulation of deeply conserved gene networks, such that exceptional phenotypic diversification coexists with remarkably conserved generative processes. Establishing the causal reciprocal links between ongoing neutral expansion of genomic architecture, emergent features of organisms' functionality, and often precisely adaptive phenotypic diversification therefore becomes an important goal of evolutionary biology and is the latest reincarnation of the search for a framework that links development, functioning and evolution of phenotypes. Here I examine, in the light of recent empirical advances, two evolutionary concepts that are central to this framework-natural selection and inheritance-the general rules by which they become associated with emergent developmental and homeostatic processes and the role that they play in descent with modification.     

The role of founder effects on the evolution of reproductive isolation

Several theories argue that large changes in allele frequencies through genetic drift after a small founding population becomes allopatrically isolated can lead to significant changes in reproductive isolation and thus trigger the origin of new species. For this reason, founder speciation has been proposed as a potent force in the generation of new species. Nonetheless, the relative importance of such ‘founder effects’ remains largely untested. In this report, I used experimental evolution to create one thousand replicates that underwent an extreme bottleneck and to study whether founder effects can lead to an increase in reproductive isolation in Drosophila yakuba. Even though the most common outcome of inbreeding is extinction, founder effects can lead to increased premating reproductive isolation in a very small proportion of cases. Changes in reproductive isolation after a founding population bottleneck are similar to changes in other phenotypic traits, in which inbreeding might displace the mean phenotypic value and substantially increase the phenotypic variance. This increase in phenotypic variance does not confer an increase in the response to selection for reproductive isolation in artificial selection experiments, indicating that the increased phenotypic variance is not caused by increases in additive genetic variance. These results also demonstrate that, similar to morphological and life‐history traits, behavioural traits can be affected by inbreeding and genetic drift.     

Evolution of phenotypic plasticity: patterns of plasticity and the emergence of ecotypes

Phenotypic plasticity itself evolves, as does any other quantitative trait. A very different question is whether phenotypic plasticity causes evolution or is a major evolutionary mechanism. Existing models of the evolution of phenotypic plasticity cover many of the proposals in the literature about the role of phenotypic plasticity in evolution. I will extend existing models to cover adaptation to a novel environment, the appearance of ecotypes and possible covariation between phenotypic plasticity and mean trait value of ecotypes. Genetic assimilation does not sufficiently explain details of observed patterns. Phenotypic plasticity as a major mechanism for evolution--such as, invading new niches, speciation or macroevolution--has, at present, neither empirical nor model support.     

Evolutionary branching under asymmetric competition

I investigate the evolution of a continuous trait, such as body size or arms level, which affects the outcome of competitive contests such that the contestant with the larger trait value has a higher probability of winning. I show that a polymorphism of distinctly different strategies can evolve in an initially monomorphic population even if mutations have only small phenotypic effect. In a simple Lotka-Volterra-type model of asymmetric competition, I derive the conditions under which two strategies can gradually evolve from a single ancestral strategy; the evolution of higher level polymorphisms is studied by numerical analysis and computer simulations of specific examples. High levels of polymorphism may build up during evolution. The coevolution of strategies in polymorphic populations, however, may also lead to extinction, which decreases the level of polymorphism. I discuss whether the evolution of several haploid strategies from a single initial strategy may correspond to the evolution of several sympatric species in a diploid outbreeding population.     

Parallel evolution and inheritance of quantitative traits

Parallel phenotypic evolution, the independent evolution of the same trait in closely related lineages, is interesting because it tells us about the contribution of natural selection to phenotypic evolution. Haldane and others have proposed that parallel evolution also results from a second process, the similarly biased production of genetic variation in close relatives, an idea that has received few tests. We suggest that influence of shared genetic biases should be detectable by the disproportionate use of the same genes in independent instances of parallel phenotypic evolution. We show how progress in testing this prediction can be made through simple tests of parallel inheritance of genetic differences: similar additive, dominance, and epistasis components in analysis of line means and similar effective numbers of loci. We demonstrate parallel inheritance in two traits, lateral plate number and body shape, in two lineages of threespine stickleback that have adapted independently to freshwater streams on opposite sides of the Pacific Ocean. Notably, reduction of plate number in freshwater involves a substitution at the same major locus in both lineages. Our results represent only a first step in the study of the genetics of parallel phenotypic evolution in sticklebacks. Nevertheless, we have shown how such studies can be employed to test the genetic hypothesis of parallel evolution and how study of parallel evolution might yield insights into the roles of both selection and genetic constraint in phenotypic evolution.     

Near-periodic substitution and the genetic variance induced by environmental change

We investigate a model that describes the evolution of a diploid sexual population in a changing environment. Individuals have discrete generations and are subject to selection on the phenotypic value of a quantitative trait, which is controlled by a finite number of bialleic loci. Environmental change is taken to lead to a uniformly changing optimal phenotypic value. The population continually adapts to the changing environment, by allelic substitution, at the loci controlling the trait. We investigate the detailed interrelation between the process of allelic substitution and the adaptation and variation of the population, via infinite population calculations and finite population simulations. We find a simple relation between the substitution rate and the rate of change of the optimal phenotypic value.     

Neutral mutation as the source of genetic variation in life history traits

The mechanism underlying the maintenance of adaptive genetic variation is a long-standing question in evolutionary genetics. There are two concepts (mutation-selection balance and balancing selection) which are based on the phenotypic differences between alleles. Mutation - selection balance and balancing selection cannot properly explain the process of gene substitution, i.e. the molecular evolution of quantitative trait loci affecting fitness. I assume that such loci have non-essential functions (small effects on fitness), and that they have the potential to evolve into new functions and acquire new adaptations. Here I show that a high amount of neutral polymorphism at these loci can exist in real populations. Consistent with this, I propose a hypothesis for the maintenance of genetic variation in life history traits which can be efficient for the fixation of alleles with very small selective advantage. The hypothesis is based on neutral polymorphism at quantitative trait loci and both neutral and adaptive gene substitutions. The model of neutral - adaptive conversion (NAC) assumes that neutral alleles are not neutral indefinitely, and that in specific and very rare situations phenotypic (relative fitness) differences between them can appear. In this paper I focus on NAC due to phenotypic plasticity of neutral alleles. The important evolutionary consequence of NAC could be the increased adaptive potential of a population. Loci responsible for adaptation should be fast evolving genes with minimally discernible phenotypic effects, and the recent discovery of genes with such characteristics implicates them as suitable candidates for loci involved in adaptation.