The effect of development on the direction of evolution: toward a twenty-first century consensus

Summary One of the most important questions in evolutionary biology is: what orients the evolutionary process? That is, what causes evolution to proceed toward certain developmental trajectories, and hence phenotypes, rather than others? In particular, there has been prolonged controversy over whether the direction of evolution is determined solely by external factors or whether the nature of the ontogenetic process, and the ways in which it can be altered by mutations in developmental genes, may also play a major role. Here, I examine this issue, concentrating on the following: the possible evolutionary orienting role of “developmental bias;” the question of whether selection can and/or will break bias; the extent to which bias is already incorporated in quantitative genetic studies; and ways of approaching the possible role of bias in the origin of evolutionary novelties. Finally, I suggest that developmental bias may provide a focal point for the coming together of conceptual and practical approaches to evo‐devo.     

Animal learning as a source of developmental bias

As a form of adaptive plasticity that allows organisms to shift their phenotype toward the optimum, learning is inherently a source of developmental bias. Learning may be of particular significance to the evolutionary biology community because it allows animals to generate adaptively biased novel behavior tuned to the environment and, through social learning, to propagate behavioral traits to other individuals, also in an adaptively biased manner. We describe several types of developmental bias manifest in learning, including an adaptive bias, historical bias, origination bias, and transmission bias, stressing that these can influence evolutionary dynamics through generating nonrandom phenotypic variation and/or nonrandom environmental states. Theoretical models and empirical data have established that learning can impose direction on adaptive evolution, affect evolutionary rates (both speeding up and slowing down responses to selection under different conditions) and outcomes, influence the probability of populations reaching global optimum, and affect evolvability. Learning is characterized by highly specific, path‐dependent interactions with the (social and physical) environment, often resulting in new phenotypic outcomes. Consequently, learning regularly introduces novelty into phenotype space. These considerations imply that learning may commonly generate plasticity first evolution.     

Bias and Evolution of the Mutationally Accessible Phenotypic Space in a Developmental System

Genetic and developmental architecture may bias the mutationally available phenotypic spectrum. Although such asymmetries in the introduction of variation may influence possible evolutionary trajectories, we lack quantitative characterization of biases in mutationally inducible phenotypic variation, their genotype-dependence, and their underlying molecular and developmental causes. Here we quantify the mutationally accessible phenotypic spectrum of the vulval developmental system using mutation accumulation (MA) lines derived from four wild isolates of the nematodes Caenorhabditis elegans and C. briggsae. The results confirm that on average, spontaneous mutations degrade developmental precision, with MA lines showing a low, yet consistently increased, proportion of developmental defects and variants. This result indicates strong purifying selection acting to maintain an invariant vulval phenotype. Both developmental system and genotype significantly bias the spectrum of mutationally inducible phenotypic variants. First, irrespective of genotype, there is a developmental bias, such that certain phenotypic variants are commonly induced by MA, while others are very rarely or never induced. Second, we found that both the degree and spectrum of mutationally accessible phenotypic variation are genotype-dependent. Overall, C. briggsae MA lines exhibited a two-fold higher decline in precision than the C. elegans MA lines. Moreover, the propensity to generate specific developmental variants depended on the genetic background. We show that such genotype-specific developmental biases are likely due to cryptic quantitative variation in activities of underlying molecular cascades. This analysis allowed us to identify the mutationally most sensitive elements of the vulval developmental system, which may indicate axes of potential evolutionary variation. Consistent with this scenario, we found that evolutionary trends in the vulval system concern the phenotypic characters that are most easily affected by mutation. This study provides an empirical assessment of developmental bias and the evolution of mutationally accessible phenotypes and supports the notion that such bias may influence the directions of evolutionary change.     

Genotype networks shed light on evolutionary constraints

An evolutionary constraint is a bias or limitation in phenotypic variation that a biological system produces. One can distinguish physicochemical, selective, genetic and developmental causes of such constraints. Here, I discuss these causes in three classes of system that bring forth many phenotypic traits and evolutionary innovations: regulatory circuits, macromolecules and metabolic networks. In these systems, genotypes with the same phenotype form large genotype networks that extend throughout a vast genotype space. Such genotype networks can help unify different causes of evolutionary constraints. They can show that these causes ultimately emerge from the process of development; that is, how phenotypes form from genotypes. Furthermore, they can explain important consequences of constraints, such as punctuated stasis and canalization.     

Historical and philosophical perspectives on the study of developmental bias

Throughout the recent history of research at the intersection of evolution and development, notions such as developmental constraint, evolutionary novelty, and evolvability have been prominent, but the term “developmental bias” has scarcely been used. And one may even doubt whether a unique and principled definition of bias is possible. I argue that the concept of developmental bias can still play a vital scientific role by means of setting an explanatory agenda that motivates investigation and guides the formulation of integrative explanatory frameworks. Less crucial is a definition that would classify patterns of phenotypic variation and unify variational patterns involving different traits and taxa as all being “bias.” Instead, what we should want is a concept that generates intellectual identity across various researchers, and that unites the diverse fields and approaches relevant to the study of developmental bias, from paleontology to behavioral biology. I point to some advantages of conducting research specifically under the label of “developmental bias,” compared with employing other, more common terms such as “evolvability.”     

ONTOGENETIC VARIATION IN PATTERNS OF PHENOTYPIC INTEGRATION IN THE LABORATORY RAT

I used confirmatory factor analysis to evaluate the ability of causal developmental models to predict observed phenotypic integration in limb and skull measures at five stages of postnatal ontogeny in the laboratory rat. To analyze the dynamics of phenotypic integration, I fit successive age-classes simultaneously to a common model. Growth was the principal developmental explanation of observed phenotypic covariation in the limb and skull. No complex morphogenetic model more adequately reconstructed observed covariance structure. Models that could not be interpreted in embryological terms, coupled with a growth component, provide the best models for observed phenotypic integration. During postnatal growth, some aspects of integration vary in both the skull and limb. The covariance between factors and the proportion of variance unique to each character differ between some sequential age-classes. The factor-pattern is invariant in the limb; however, repatterning in the skull occurs in the interval between eye-opening and weaning. The temporal variation in the structure of covariation suggests that functional interactions among characters may create observed patterns of phenotypic integration. The developmental constraints responsible for evolutionary modification of phenotypes might be equally dynamic and responsive to embryonic functional interactions.     

Does phenotypic plasticity initiate developmental bias?

The generation of variation is paramount for the action of natural selection. Although biologists are now moving beyond the idea that random mutation provides the sole source of variation for adaptive evolution, we still assume that variation occurs randomly. In this review, we discuss an alternative view for how phenotypic plasticity, which has become well accepted as a source of phenotypic variation within evolutionary biology, can generate nonrandom variation. Although phenotypic plasticity is often defined as a property of a genotype, we argue that it needs to be considered more explicitly as a property of developmental systems involving more than the genotype. We provide examples of where plasticity could be initiating developmental bias, either through direct active responses to similar stimuli across populations or as the result of programmed variation within developmental systems. Such biased variation can echo past adaptations that reflect the evolutionary history of a lineage but can also serve to initiate evolution when environments change. Such adaptive programs can remain latent for millions of years and allow development to harbor an array of complex adaptations that can initiate new bouts of evolution. Specifically, we address how ideas such as the flexible stem hypothesis and cryptic genetic variation overlap, how modularity among traits can direct the outcomes of plasticity, and how the structure of developmental signaling pathways is limited to a few outcomes. We highlight key questions throughout and conclude by providing suggestions for future research that can address how plasticity initiates and harbors developmental bias.     

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.     

Natural selection. II. Developmental variability and evolutionary rate

In classical evolutionary theory, genetic variation provides the source of heritable phenotypic variation on which natural selection acts. Against this classical view, several theories have emphasized that developmental variability and learning enhance nonheritable phenotypic variation, which in turn can accelerate evolutionary response. In this paper, I show how developmental variability alters evolutionary dynamics by smoothing the landscape that relates genotype to fitness. In a fitness landscape with multiple peaks and valleys, developmental variability can smooth the landscape to provide a directly increasing path of fitness to the highest peak. Developmental variability also allows initial survival of a genotype in response to novel or extreme environmental challenge, providing an opportunity for subsequent adaptation. This initial survival advantage arises from the way in which developmental variability smooths and broadens the fitness landscape. Ultimately, the synergism between developmental processes and genetic variation sets evolutionary rate.     

METAMODELS AND PHYLOGENETIC REPLICATION: A SYSTEMATIC APPROACH TO THE EVOLUTION OF DEVELOPMENTAL PATHWAYS

Molecular genetic analysis of phenotypic variation has revealed many examples of evolutionary change in the developmental pathways that control plant and animal morphology. A major challenge is to integrate the information from diverse organisms and traits to understand the general patterns of developmental evolution. This integration can be facilitated by evolutionary metamodels—traits that have undergone multiple independent changes in different species and whose development is controlled by well-studied regulatory pathways. The metamodel approach provides the comparative equivalent of experimental replication, allowing us to test whether the evolution of each developmental pathway follows a consistent pattern, and whether different pathways are predisposed to different modes of evolution by their intrinsic organization. A review of several metamodels suggests that the structure of developmental pathways may bias the genetic basis of phenotypic evolution, and highlights phylogenetic replication as a value-added approach that produces deeper insights into the mechanisms of evolution than single-species analyses.     

The Baldwin effect and genetic assimilation: revisiting two mechanisms of evolutionary change mediated by phenotypic plasticity

Two different, but related, evolutionary theories pertaining to phenotypic plasticity were proposed by James Mark Baldwin and Conrad Hal Waddington. Unfortunately, these theories are often confused with one another. Baldwin's notion of organic selection posits that plasticity influences whether an individual will survive in a new environment, thus dictating the course of future evolution. Heritable variations can then be selected upon to direct phenotypic evolution (i.e., "orthoplasy"). The combination of these two processes (organic selection and orthoplasy) is now commonly referred to as the "Baldwin effect." Alternately, Waddington's genetic assimilation is a process whereby an environmentally induced phenotype, or "acquired character," becomes canalized through selection acting upon the developmental system. Genetic accommodation is a modern term used to describe the process of heritable changes that occur in response to a novel induction. Genetic accommodation is a key component of the Baldwin effect, and genetic assimilation is a type of genetic accommodation. I here define both the Baldwin effect and genetic assimilation in terms of genetic accommodation, describe cases in which either should occur in nature, and propose that each could play a role in evolutionary diversification.     

The extended evolutionary synthesis: its structure,assumptions and predictions

Scientific activities take place within the structured sets of ideas and assumptions that define a field and its practices. The conceptual framework of evolutionary biology emerged with the Modern Synthesis in the early twentieth century and has since expanded into a highly successful research program to explore the processes of diversification and adaptation. Nonetheless, the ability of that framework satisfactorily to accommodate the rapid advances in developmental biology, genomics and ecology has been questioned. We review some of these arguments, focusing on literatures (evo-devo, developmental plasticity, inclusive inheritance and niche construction) whose implications for evolution can be interpreted in two ways—one that preserves the internal structure of contemporary evolutionary theory and one that points towards an alternative conceptual framework. The latter, which we label the ‘extended evolutionary synthesis'' (EES), retains the fundaments of evolutionary theory, but differs in its emphasis on the role of constructive processes in development and evolution, and reciprocal portrayals of causation. In the EES, developmental processes, operating through developmental bias, inclusive inheritance and niche construction, share responsibility for the direction and rate of evolution, the origin of character variation and organism–environment complementarity. We spell out the structure, core assumptions and novel predictions of the EES, and show how it can be deployed to stimulate and advance research in those fields that study or use evolutionary biology.     

Developmental bias in evolution: evolutionary accessibility of phenotypes in a model evo-devo system

SUMMARY The success of the modern synthesis has resulted in forces of evolutionary change other than natural selection being marginalized. However, recent work has attempted to show the importance of non-selective influences in shaping organic form. One such force is developmental bias, in which phenotypes are differentially produced. We use a simulation model of neural development to explore questions of general interest about developmental systems. From this analysis, we find that the pattern of developmental bias varies strongly with the genotype even among phenotypically-neutral genotypes. In addition to this genotype-dependent developmental bias ( local bias ), an intrinsic bias exists in the developmental system ( global bias ). We also show that developmental bias varies among related genotypes that produce the same phenotype. Finally, we illustrate how a pattern of bias emerges from the manner in which mutations affect the regulatory structure of the wild-type genotype. These results suggest that developmental bias could have a strong influence on the direction of evolutionary modification.     

A conceptual framework of evolutionary novelty and innovation

Since 1990 the recognition of deep homologies among metazoan developmental processes and the spread of more mechanistic approaches to developmental biology have led to a resurgence of interest in evolutionary novelty and innovation. Other evolutionary biologists have proposed central roles for behaviour and phenotypic plasticity in generating the conditions for the construction of novel morphologies, or invoked the accessibility of new regions of vast sequence spaces. These approaches contrast with more traditional emphasis on the exploitation of ecological opportunities as the primary source of novelty. This definitional cornucopia reflects differing stress placed on three attributes of novelties: their radical nature, the generation of new taxa, and ecological and evolutionary impact. Such different emphasis has led to conflating four distinct issues: the origin of novel attributes (genes, developmental processes, phenotypic characters), new functions, higher clades and the ecological impact of new structures and functions. Here I distinguish novelty (the origin of new characters, deep character transformations, or new combinations) from innovation, the ecological and evolutionary success of clades. Evidence from the fossil record of macroevolutionary lags between the origin of a novelty and its ecological success demonstrates that novelty may be decoupled from innovation, and only definitions of novelty based on radicality (rather than generativity or consequentiality) can be assessed without reference to the subsequent history of the clade to which a novelty belongs. These considerations suggest a conceptual framework for novelty and innovation, involving: (i) generation of the potential for novelty; (ii) the formation of novel attributes; (iii) refinement of novelties through adaptation; (iv) exploitation of novelties by a clade, which may coincide with a new round of ecological or environmental potentiation; followed by (v) the establishment of innovations through ecological processes. This framework recognizes that there is little empirical support for either the dominance of ecological opportunity, nor abrupt discontinuities (often caricatured as ‘hopeful monsters’). This general framework may be extended to aspects of cultural and social innovation.     

Developmental drive: an important determinant of the direction of phenotypic evolution

SUMMARY Over any period of evolutionary time, the prevailing ontogenetic trajectory within a lineage may either recur unchanged from generation to generation (stasis) or alter (developmental reprogramming). A key question about reprogramming is whether it exhibits intrinsic biases in favor of some sorts of change and against others, which may be referred to respectively as "drive" and "constraint." A simple logical argument suggests that both drive and constraint should be common, and conversely that cases of equiprobable modification in various phenotypic directions should be relatively rare. These proposals, that drive and constraint exist and that they are common, appear to be widely accepted, even among neo-Darwinians, who are sometimes portrayed as rejecting them. What is more controversial is that developmental drive (and constraint) can have a powerful influence on the direction of evolutionary change. It is argued that such an influence will occur, and indeed may be pervasive.     

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 concept of developmental reprogramming and the quest for an inclusive theory of evolutionary mechanisms

SUMMARY Evolutionary developmental biology has already made a major contribution to our understanding of evolutionary patterns, notably homology. However, while it has the potential to make an equally important contribution to our understanding of evolutionary mechanisms, and indeed to the integration of mechanism and pattern, it has not yet done so. This paper explores how this potential may be realized. In particular, I focus on the limitations of present-day neo-Darwinian theory, and indicate how a combination of the neo-Darwinian and "evo-devo" approaches provides a more inclusive view of evolutionary mechanisms with greater explanatory power. There is a particular focus on developmental reprogramming, which lies logically between mutation and selection, yet has been neglected in mainstream evolutionary theory. The inclusion of developmental reprogramming in the list of evolutionary mechanisms leads to a view that the direction of evolutionary change is determined by a combination of internal and external factors, rather than being controlled entirely by the environment.     

Evolutionary developmental biology and genomics

Reciprocal questions often frame studies of the evolution of developmental mechanisms. How can species share similar developmental genetic toolkits but still generate diverse life forms? Conversely, how can similar forms develop from different toolkits? Genomics bridges the gap between evolutionary and developmental biology, and can help answer these evo-devo questions in several ways. First, it informs us about historical relationships, thus orienting the direction of evolutionary diversification. Second, genomics lists all toolkit components, thereby revealing contraction and expansion of the genome and suggesting mechanisms for evolution of both developmental functions and genome architecture. Finally, comparative genomics helps us to identify conserved non-coding elements and their relationship to genome architecture and development.     

Evolvability of cell specification mechanisms

The architecture of gene action during development is relevant to phenotypic evolution as it links genotype to morphological phenotype. Analysis of development at the level of cell fate specification mechanisms illuminates some of the properties of developmental evolution. In this article, we first review examples of evolutionary change in mechanisms of cell fate specification, with an emphasis on evolution in the dependence on inductive signaling and on evolution of the mechanisms that result in spatial asymmetries. We then focus on properties of development that bias possible phenotypic change and present how the distribution of phenotypes that are available by mutational change of the starting genotype can be experimentally tested by systematic mutagenesis. We finally discuss ways in which selection pressures on phenotypes can be inferred from a comparison of the phenotypic spectrum found on mutation with that found in the wild.