The role of epistatic gene interactions in the response to selection and the evolution of evolvability

It has been argued that the architecture of the genotype-phenotype map determines evolvability, but few studies have attempted to quantify these effects. In this article we use the multilinear epistatic model to study the effects of different forms of epistasis on the response to directional selection. We derive an analytical prediction for the change in the additive genetic variance, and use individual-based simulations to understand the dynamics of evolvability and the evolution of genetic architecture. This shows that the major determinant for the evolution of the additive variance, and thus the evolvability, is directional epistasis. Positive directional epistasis leads to an acceleration of evolvability, while negative directional epistasis leads to canalization. In contrast, pure non-directional epistasis has little effect on the response to selection. One consequence of this is that the classical epistatic variance components, which do not distinguish directional and non-directional effects, are useless as predictors of evolutionary dynamics. The build-up of linkage disequilibrium also has negligible effects. We argue that directional epistasis is likely to have major effects on evolutionary dynamics and should be the focus of empirical studies of epistasis.     

Genes,development, and evolvability in primate evolution

Development is the process whereby a fertilized cell becomes a mature individual. In metazoans, this complex process involves the differentiation of somatic cells into committed cell and tissue types; the organization and migration of cells, tissues, and anatomical structures relative to one another; and growth. 1 Development matters to evolution in two ways. First, development carries out heritable genetic instructions contained in zygotes to produce functioning yet phenotypically varied individuals. At the population level, this variation in form and function among individuals provides the “raw material” for evolution. Second, the mechanisms of development influence the magnitude, direction, and interdependence of heritable phenotypic variation among traits. Together with phenomena such as genetic drift, organismal development determines the raw material available to selection and thus influences the rate and direction of phenotypic evolution. 2 , 3     

Typology now: homology and developmental constraints explain evolvability

By linking the concepts of homology and morphological organization to evolvability, this paper attempts to (1) bridge the gap between developmental and phylogenetic approaches to homology and to (2) show that developmental constraints and natural selection are compatible and in fact complementary. I conceive of a homologue as a unit of morphological evolvability, i.e., as a part of an organism that can exhibit heritable phenotypic variation independently of the organism’s other homologues. An account of homology therefore consists in explaining how an organism’s developmental constitution results in different homologues/characters as units that can evolve independently of each other. The explanans of an account of homology is developmental, yet the very explanandum is an evolutionary phenomenon: evolvability in a character-by-character fashion, which manifests itself in phylogenetic patterns as recognized by phylogenetic approaches to homology. While developmental constraints and selection have often been viewed as antagonistic forces, I argue that both are complementary as they concern different parts of the evolutionary process. Developmental constraints, conceived of as the presence of the same set of homologues across phenotypic change, pertain to how heritable variation can be generated in the first place (evolvability), while natural selection operates subsequently on the produced variation.

The role of preadaptation,propagule pressure and competition in the colonization of new habitats

To successfully colonize new habitats, organisms not only need to gain access to it, they also need to cope with the selective pressures imposed by the local biotic and abiotic conditions. The number of immigrants, the preadaptation to the local habitat and the presence of competitors are important factors determining the success of colonization. Here, using two experimental set-ups, we studied the effect of interspecific competition in combination with propagule pressure and preadaptation on the colonization success of new habitats. Our model system consisted of tomato plants (the novel habitat), the two-spotted spider mite Tetranychus urticae as our focal species and the red spider mite Tetranychus evansi as a competitor. Our results show that propagule pressure and preadaptation positively affect colonization success. More successful populations reach larger final population sizes either by having higher per capita growth rates (due to preadaptation effects) or by starting a population with a larger number of individuals. Although populations are more successful colonizing non-competitive environments than competitive ones, propagule pressure and preadaptation counteract the negative effects of competition, promoting colonization success. Our study shows the importance of propagule pressure and preadaptation for successful colonization of new habitats by providing the ability to cope with both the exigencies of new environments and the community context.     

Measuring and comparing evolvability and constraint in multivariate characters

The Lande equation forms the basis for our understanding of the short-term evolution of quantitative traits in a multivariate context. It predicts the response to selection as the product of an additive genetic variance matrix and a selection gradient. The selection gradient approximates the force and direction of selection, and the genetic variance matrix quantifies the role of the genetic system in evolution. Attempts to understand the evolutionary significance of the genetic variance matrix are hampered by the fact that the majority of the methods used to characterize and compare variance matrices have not been derived in an explicit theoretical context. We use the Lande equation to derive new measures of the ability of a variance matrix to allow or constrain evolution in any direction in phenotype space. Evolvability captures the ability of a population to evolve in the direction of selection when stabilizing selection is absent. Conditional evolvability captures the ability of a population to respond to directional selection in the presence of stabilizing selection on other trait combinations. We then derive measures of character autonomy and integration from these evolvabilities. We study the properties of these measures and show how they can be used to interpret and compare variance matrices. As an illustration, we show that divergence of wing shape in the dipteran family Drosophilidae has proceeded in directions that have relatively high evolvabilities.     

Morphological evolution through integration: a quantitative study of cranial integration in Homo, Pan, Gorilla and Pongo

Morphological integration refers to coordinated variation among traits that are closely related in development and/or function. Patterns of integration can offer important insight into the structural relationship between phenotypic units, providing a framework to address questions about phenotypic evolvability and constraints. Integrative features of the primate cranium have recently become a popular subject of study. However, an important question that still remains under-investigated is: what is the pattern of cranial shape integration among closely related hominoids? To address this question, we conducted a Procrustes-based geometric morphometrics study to quantify and analyze shape covariation patterns between different cranial regions in Homo, Pan, Gorilla and Pongo. A total of fifty-six 3D landmarks were collected on 407 adult individuals. We then sub-divided the landmarks corresponding to cranial units as outlined in the ‘functional matrix hypothesis.’ Sub-dividing the cranium in this manner allowed us to explore patterns of covariation between the face, basicranium and cranial vault, using the two-block partial least squares approach. Our results suggest that integrated shape changes in the hominoid cranium are complex, but that the overall pattern of integration is similar among human and non-human apes. Thus, despite having very distinct morphologies the way in which the face, basicranium and cranial vault covary is shared among these taxa. These results imply that the pattern of cranial integration among hominoids is conserved.     

Evolution of evolvability in a developmental model

Evolvability, the ability of populations to adapt, can evolve through changes in the mechanisms determining genetic variation and in the processes of development. Here we construct and evolve a simple developmental model in which the pleiotropic effects of genes can evolve. We demonstrate that selection in a changing environment favors a specific pattern of variability, and that this favored pattern maximizes evolvability. Our analysis shows that mutant genotypes with higher evolvability are more likely to increase to fixation. We also show that populations of highly evolvable genotypes are much less likely to be invaded by mutants with lower evolvability, and that this dynamic primarily shapes evolvability. We examine several theoretical objections to the evolution of evolvability in light of this result. We also show that this result is robust to the presence or absence of recombination, and explore how nonrandom environmental change can select for a modular pattern of variability.     

When ontogeny reveals what phylogeny hides: gain and loss of horns during development and evolution of horned beetles

How ecological, developmental and genetic mechanisms interact in the genesis and subsequent diversification of morphological novelties is unknown for the vast majority of traits and organisms. Here we explore the ecological, developmental, and genetic underpinnings of a class of traits that is both novel and highly diverse: beetle horns. Specifically, we focus on the origin and diversification of a particular horn type, those protruding from the pronotum, in the genus Onthophagus, a particularly speciose and morphologically diverse genus of horned beetles. We begin by documenting immature development of nine Onthophagus species and show that all of these species express pronotal horns in a developmentally transient fashion in at least one or both sexes. Similar to species that retain their horns to adulthood, transient horns grow during late larval development and are clearly visible in pupae. However, unlike species that express horns as adults, transient horns are resorbed during pupal development. In a large number of species this mechanisms allows fully horned pupae to molt into entirely hornless adults. Consequently, far more Onthophagus species appear to possess the ability to develop pronotal horns than is indicated by their adult phenotypes. We use our data to expand a recent phylogeny of the genus Onthophagus to explore how the widespread existence of developmentally transient horns alters our understanding of the origin and dynamics of morphological innovation and diversification in this genus. We find that including transient horn development into the phylogeny dramatically reduces the number of independent origins required to explain extant diversity patters and suggest that pronotal horns may have originated only a few times, or possibly only once, during early Onthophagus evolution. We then propose a new and previously undescribed function for pronotal horns during immature development. We provide histological as well as experimental data that illustrate that pronotal horns are crucial for successful ecdysis of the larval head capsule during the larval-to-pupal molt, and that this molting function appears to be unique to the genus Onthophagus and absent in the other scarabaeine genera. We discuss how this additional function may help explain the existence and maintenance of developmentally transient horns, and how at least some horn types of adult beetles may have evolved as exaptations from pupal structures originally evolved to perform an unrelated function.     

Quantifying protein modularity and evolvability: A comparison of different techniques

Modularity increases evolvability by reducing constraints on adaptation and by allowing preexisting parts to function in new contexts for novel uses. Protein evolution provides an excellent context to study the causes and consequences of biological modularity. In order to address such questions, however, an index for protein modularity is necessary. This paper proposes a simple index for protein modularity-"module density"-which is the number of evolutionarily independent modules that compose a protein divided by the number of amino acids in the protein. The decomposition of proteins into constituent modules can be accomplished by either of two classes of methods. The first class of methods relies on "suppositional" criteria to assign amino acids to modules, whereas the second class of methods relies on "coevolutionary" criteria for this task. One simple and practical method from the first class consists of approximating the number of modules in a protein as the number of regular secondary structure elements (i.e., helices and sheets). Methods based on coevolutionary criteria require more elaborate data, but they have the advantage of being able to specify modules without prior assumptions about why they exist. Given the increasing availability of datasets sampling protein mutational spectra (e.g., from comparative genomics, experimental evolution, and computational prediction), methods based on coevolutionary criteria will likely become more promising in the near future. The ability to meaningfully quantify protein modularity via simple indices has the potential to aid future efforts to understand protein evolutionary rate determinants, improve molecular evolution models and engineer novel proteins.     

The effect of scale-free topology on the robustness and evolvability of genetic regulatory networks

We investigate how scale-free (SF) and Erd?s-Rényi (ER) topologies affect the interplay between evolvability and robustness of model gene regulatory networks with Boolean threshold dynamics. In agreement with Oikonomou and Cluzel (2006) we find that networks with SF_in topologies, that is SF topology for incoming nodes and ER topology for outgoing nodes, are significantly more evolvable towards specific oscillatory targets than networks with ER topology for both incoming and outgoing nodes. Similar results are found for networks with SF_both and SF_out topologies. The functionality of the SF_out topology, which most closely resembles the structure of biological gene networks (Babu et al., 2004), is compared to the ER topology in further detail through an extension to multiple target outputs, with either an oscillatory or a non-oscillatory nature. For multiple oscillatory targets of the same length, the differences between SF_out and ER networks are enhanced, but for non-oscillatory targets both types of networks show fairly similar evolvability. We find that SF networks generate oscillations much more easily than ER networks do, and this may explain why SF networks are more evolvable than ER networks are for oscillatory phenotypes. In spite of their greater evolvability, we find that networks with SF_out topologies are also more robust to mutations (mutational robustness) than ER networks. Furthermore, the SF_out topologies are more robust to changes in initial conditions (environmental robustness). For both topologies, we find that once a population of networks has reached the target state, further neutral evolution can lead to an increase in both the mutational robustness and the environmental robustness to changes in initial conditions.     

Response to selection and evolvability of invasive populations

While natural selection might in some cases facilitate invasions into novel habitats, few direct measurements of selection response exist for invasive populations. This study examined selection response to changes in salinity using the copepod Eurytemora affinis. This copepod has invaded fresh water from saline habitats multiple times independently throughout the Northern Hemisphere. Selection response to a constant intermediate salinity (5 PSU) was measured in the laboratory for saline source and freshwater invading populations from the St. Lawrence drainage (North America). These populations were reared under three conditions: (1) native salinities (0 or 15 PSU) for at least two generations, (2) 5 PSU for two generations, and (3) 5 PSU for six generations. Full-sib clutches taken from populations reared under these three conditions were split across four salinities (0, 5, 15, and 25 PSU) to determine reaction norms for survival and development time. Contrasts in survival and development time across the three rearing conditions were treated as the selection response. Selection at 5 PSU resulted in a significant decline in freshwater (0 PSU) tolerance for both the saline and freshwater populations. Yet, evolutionary differences in freshwater tolerance persisted between the saline and freshwater populations. The saline and freshwater populations converged in their high-salinity (25 PSU) tolerance, with an increase in the freshwater population and decline in the saline population. Development time did not shift greatly in response to selection at 5 PSU. For all three rearing conditions, the freshwater population exhibited retarded larval development and accelerated juvenile development relative to the saline population. Results from this study indicate that both the saline and freshwater populations exhibit significant responses to selection for a fitness-related trait critical for invasions into a novel habitat. For the Symposium on “Evolvability and Adaptation of Invasive Species,” Society for the Study of Evolution 2004.     

Serial homology and the evolution of mammalian limb covariation structure

The tetrapod forelimb and hindlimb are serially homologous structures that share a broad range of developmental pathways responsible for their patterning and outgrowth. Covariation between limbs, which can introduce constraints on the production of variation, is related to the duplication of these developmental factors. Despite this constraint, there is remarkable diversity in limb morphology, with a variety of functional relationships between and within forelimb and hindlimb elements. Here we assess a hierarchical model of limb covariation structure based on shared developmental factors. We also test whether selection for morphologically divergent forelimbs or hindlimbs is associated with reduced covariation between limbs. Our sample includes primates, murines, a carnivoran, and a chiropteran that exhibit varying degrees of forelimb and hindlimb specialization, limb size divergence, and/or phylogenetic relatedness. We analyze the pattern and significance of between-limb morphological covariation with linear distance data collected using standard morphometric techniques and analyzed by matrix correlations, eigenanalysis, and partial correlations. Results support a common limb covariation structure across these taxa and reduced covariation between limbs in nonquadruped species. This result indicates that diversity in limb morphology has evolved without signficant modifications to a common covariation structure but that the higher degree of functional limb divergence in bats and, to some extent, gibbons is associated with weaker integration between limbs. This result supports the hypothesis that limb divergence, particularly selection for increased functional specialization, involves the reduction of developmental factors common to both limbs, thereby reducing covariation.     

Sexual selection and the evolution of evolvability

Here we show that sexual selection can have an effect on the rate of mutation. We simulated the fate of a genetic modifier of the mutation rate in a sexual population with and without sexual selection (modelled using a female choice mechanism). Female choice for 'good genes' should reduce variability among male subjects, leaving insufficient differences to maintain female preferences. However, female choice can actually increase genetic variability by supporting a higher mutation rate in sexually selected traits. Increasing the mutation rate will be selected against because of the resulting decline in mean fitness. However, it also increases the probability of rare beneficial mutations arising, and mating skew caused by female preferences for male subjects carrying those beneficials with few deleterious mutations ('good genes') can lead to a mutation rate above that expected under natural selection. A choice of two male subjects was sufficient for there to be a twofold increase in the mutation rate as opposed to a decrease found under random mating.     

Pleiotropy and preadaptation in the evolution of human language capacity

The capacity for spoken language in the human is a genetic trait, but the information communicated by this means is to a large extent culturally determined. Using a gene-culture coevolutionary approach, we model the hypothesis that speech evolved as a channel for the communication of adaptive cultural traits from parent to offspring. The motivation for this paper is a condition obtained previously that initial increase of communication would require at least a two-fold advantage for the transmitted trait. Here, we show that under reasonable assumptions the invasion condition becomes less stringent. In Model 1, we assume that two adaptive cultural traits can be transmitted. A gene which permits communication of the second adaptive trait. In Model 2, we assume that a related function such as greater memory capacity is a prerequisite for speech, and that this function confers an advantage independent of its association with speech. In both models we assume haploid sexual genetics and a simple scheme of vertical transmission. The stability properties of all corner and edge equilibria of the models are analyzed. The two models taken together suggest a possible scenario for the initial stages of the evolution of speech.     

Interactions between locomotion,feeding, and bodily elongation during the evolution of snakes

Information from lizard lineages that have evolved a highly elongate (snake‐like) body form may clarify the selective forces important in the early evolution of snakes. Lizards have evolved bodily elongation via two distinct routes: as an adaptation to burrowing underground or to rapid locomotion above ground. These two routes involve diametrically opposite modifications to the body plan. Burrowing lizards have elongate trunks, small heads, short tails, and relatively constant body widths, whereas surface‐active taxa typically have shorter trunks, wider heads, longer tails, and more variable body widths. Snakes resemble burrowing rather than surface‐active (or aquatic) lizards in these respects, suggesting that snakes evolved from burrowing lizards. The trunk elongation of burrowing lizards increases the volume of the alimentary tract, so that an ability to ingest large meals (albeit consisting of small individual prey items) was present in the earliest snakes. Subsequent shifts to ingestion of wide‐bodied prey came later, after selection dismantled other gape‐constraining morphological attributes, some of which may also have arisen as adaptations to burrowing through hard soil (e.g. relatively small heads, rigid skulls). Adaptations of snake skulls to facilitate ingestion of large prey have evolved to compensate for the reduction of relative head size accompanying bodily elongation; relative to predator body mass, maximum sizes of prey taken by snakes may not be much larger than those of many lizards. This adaptive scenario suggests novel functional links between traits, and a series of testable predictions about the relationships between squamate morphology, habitat, and trophic ecology. © 2008 The Linnean Society of London, Biological Journal of the Linnean Society, 2008, 95 , 293–304.     

The mutation matrix and the evolution of evolvability

Evolvability is a key characteristic of any evolving system, and the concept of evolvability serves as a unifying theme in a wide range of disciplines related to evolutionary theory. The field of quantitative genetics provides a framework for the exploration of evolvability with the promise to produce insights of global importance. With respect to the quantitative genetics of biological systems, the parameters most relevant to evolvability are the G-matrix, which describes the standing additive genetic variances and covariances for a suite of traits, and the M-matrix, which describes the effects of new mutations on genetic variances and covariances. A population's immediate response to selection is governed by the G-matrix. However, evolvability is also concerned with the ability of mutational processes to produce adaptive variants, and consequently the M-matrix is a crucial quantitative genetic parameter. Here, we explore the evolution of evolvability by using analytical theory and simulation-based models to examine the evolution of the mutational correlation, r(mu), the key parameter determining the nature of genetic constraints imposed by M. The model uses a diploid, sexually reproducing population of finite size experiencing stabilizing selection on a two-trait phenotype. We assume that the mutational correlation is a third quantitative trait determined by multiple additive loci. An individual's value of the mutational correlation trait determines the correlation between pleiotropic effects of new alleles when they arise in that individual. Our results show that the mutational correlation, despite the fact that it is not involved directly in the specification of an individual's fitness, does evolve in response to selection on the bivariate phenotype. The mutational variance exhibits a weak tendency to evolve to produce alignment of the M-matrix with the adaptive landscape, but is prone to erratic fluctuations as a consequence of genetic drift. The interpretation of this result is that the evolvability of the population is capable of a response to selection, and whether this response results in an increase or decrease in evolvability depends on the way in which the bivariate phenotypic optimum is expected to move. Interestingly, both analytical and simulation results show that the mutational correlation experiences disruptive selection, with local fitness maxima at -1 and +1. Genetic drift counteracts the tendency for the mutational correlation to persist at these extreme values, however. Our results also show that an evolving M-matrix tends to increase stability of the G-matrix under most circumstances. Previous studies of G-matrix stability, which assume nonevolving M-matrices, consequently may overestimate the level of instability of G relative to what might be expected in natural systems. Overall, our results indicate that evolvability can evolve in natural systems in a way that tends to result in alignment of the G-matrix, the M-matrix, and the adaptive landscape, and that such evolution tends to stabilize the G-matrix over evolutionary time.     

Evolution of adaptive phenotypic variation patterns by direct selection for evolvability

A basic assumption of the Darwinian theory of evolution is that heritable variation arises randomly. In this context, randomness means that mutations arise irrespective of the current adaptive needs imposed by the environment. It is broadly accepted, however, that phenotypic variation is not uniformly distributed among phenotypic traits, some traits tend to covary, while others vary independently, and again others barely vary at all. Furthermore, it is well established that patterns of trait variation differ among species. Specifically, traits that serve different functions tend to be less correlated, as for instance forelimbs and hind limbs in bats and humans, compared with the limbs of quadrupedal mammals. Recently, a novel class of genetic elements has been identified in mouse gene-mapping studies that modify correlations among quantitative traits. These loci are called relationship loci, or relationship Quantitative Trait Loci (rQTL), and affect trait correlations by changing the expression of the existing genetic variation through gene interaction. Here, we present a population genetic model of how natural selection acts on rQTL. Contrary to the usual neo-Darwinian theory, in this model, new heritable phenotypic variation is produced along the selected dimension in response to directional selection. The results predict that selection on rQTL leads to higher correlations among traits that are simultaneously under directional selection. On the other hand, traits that are not simultaneously under directional selection are predicted to evolve lower correlations. These results and the previously demonstrated existence of rQTL variation, show a mechanism by which natural selection can directly enhance the evolvability of complex organisms along lines of adaptive change.     

Phenotypic integration and the evolution of signal repertoires: A case study of treefrog acoustic communication

Animal signals are inherently complex phenotypes with many interacting parts combining to elicit responses from receivers. The pattern of interrelationships between signal components reflects the extent to which each component is expressed, and responds to selection, either in concert with or independently of others. Furthermore, many species have complex repertoires consisting of multiple signal types used in different contexts, and common morphological and physiological constraints may result in interrelationships extending across the multiple signals in species’ repertoires. The evolutionary significance of interrelationships between signal traits can be explored within the framework of phenotypic integration, which offers a suite of quantitative techniques to characterize complex phenotypes. In particular, these techniques allow for the assessment of modularity and integration, which describe, respectively, the extent to which sets of traits covary either independently or jointly. Although signal and repertoire complexity are thought to be major drivers of diversification and social evolution, few studies have explicitly measured the phenotypic integration of signals to investigate the evolution of diverse communication systems. We applied methods from phenotypic integration studies to quantify integration in the two primary vocalization types (advertisement and aggressive calls) in the treefrogs Hyla versicolor, Hyla cinerea, and Dendropsophus ebraccatus. We recorded male calls and calculated standardized phenotypic variance–covariance ( P ) matrices for characteristics within and across call types. We found significant integration across call types, but the strength of integration varied by species and corresponded with the acoustic similarity of the call types within each species. H. versicolor had the most modular advertisement and aggressive calls and the least acoustically similar call types. Additionally, P was robust to changing social competition levels in H. versicolor. Our findings suggest new directions in animal communication research in which the complex relationships among the traits of multiple signals are a key consideration for understanding signal evolution.