PERSPECTIVE: COMPLEX ADAPTATIONS AND THE EVOLUTION OF EVOLVABILITY

The problem of complex adaptations is studied in two largely disconnected research traditions: evolutionary biology and evolutionary computer science. This paper summarizes the results from both areas and compares their implications. In evolutionary computer science it was found that the Darwinian process of mutation, recombination and selection is not universally effective in improving complex systems like computer programs or chip designs. For adaptation to occur, these systems must possess “evolvability,” i.e., the ability of random variations to sometimes produce improvement. It was found that evolvability critically depends on the way genetic variation maps onto phenotypic variation, an issue known as the representation problem. The genotype-phenotype map determines the variability of characters, which is the propensity to vary. Variability needs to be distinguished from variations, which are the actually realized differences between individuals. The genotype-phenotype map is the common theme underlying such varied biological phenomena as genetic canalization, developmental constraints, biological versatility, developmental dissociability, and morphological integration. For evolutionary biology the representation problem has important implications: how is it that extant species acquired a genotype-phenotype map which allows improvement by mutation and selection? Is the genotype-phenotype map able to change in evolution? What are the selective forces, if any, that shape the genotype-phenotype map? We propose that the genotype-phenotype map can evolve by two main routes: epistatic mutations, or the creation of new genes. A common result for organismic design is modularity. By modularity we mean a genotype-phenotype map in which there are few pleiotropic effects among characters serving different functions, with pleiotropic effects falling mainly among characters that are part of a single functional complex. Such a design is expected to improve evolvability by limiting the interference between the adaptation of different functions. Several population genetic models are reviewed that are intended to explain the evolutionary origin of a modular design. While our current knowledge is insufficient to assess the plausibility of these models, they form the beginning of a framework for understanding the evolution of the genotype-phenotype map.     

Genetics, development and evolution of adaptive pigmentation in vertebrates

The study of pigmentation has played an important role in the intersection of evolution, genetics, and developmental biology. Pigmentation's utility as a visible phenotypic marker has resulted in over 100 years of intense study of coat color mutations in laboratory mice, thereby creating an impressive list of candidate genes and an understanding of the developmental mechanisms responsible for the phenotypic effects. Variation in color and pigment patterning has also served as the focus of many classic studies of naturally occurring phenotypic variation in a wide variety of vertebrates, providing some of the most compelling cases for parallel and convergent evolution. Thus, the pigmentation model system holds much promise for understanding the nature of adaptation by linking genetic changes to variation in fitness-related traits. Here, I first discuss the historical role of pigmentation in genetics, development and evolutionary biology. I then discuss recent empirically based studies in vertebrates, which rely on these historical foundations to make connections between genotype and phenotype for ecologically important pigmentation traits. These studies provide insight into the evolutionary process by uncovering the genetic basis of adaptive traits and addressing such long-standing questions in evolutionary biology as (1) are adaptive changes predominantly caused by mutations in regulatory regions or coding regions? (2) is adaptation driven by the fixation of dominant mutations? and (3) to what extent are parallel phenotypic changes caused by similar genetic changes? It is clear that coloration has much to teach us about the molecular basis of organismal diversity, adaptation and the evolutionary process.     

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.     

Trait independence primes convergent trait loss

The repeated, independent evolution of traits (convergent evolution) is often attributed to shared environmental selection pressures. However, developmental dependencies among traits can limit the phenotypic variation available to selection and bias evolutionary outcomes. Here, we determine how changes in developmentally correlated traits may impact convergent loss of the tympanic middle ear, a highly labile trait within toads that currently lack adaptive explanation. The middle ear's lability could reflect evolutionary trade‐offs with other skull features under selection, or the middle ear may evolve independently of the rest of the skull, allowing it to be modified by active or passive processes without pleiotropic trade‐offs with other skull features. We compare the skulls of 55 species (39 eared, 16 earless) within the family Bufonidae, spanning six hypothesized independent middle ear transitions. We test whether shared or lineage‐specific changes in skull shape distinguish earless species from eared species and whether earless skulls lack other late‐forming skull bones. We find no evidence for pleiotropic trade‐offs between the middle ear and other skull structures. Instead, middle ear loss in anurans may provide a rare example of developmental independence contributing to evolutionary lability of a sensory system.     

A test of Darwin's ‘lop‐eared’ rabbit hypothesis

Integration of evolutionary and developmental biology has stimulated novel insights on the origins and maintenance of phenotypic variation. For instance, phenotypic accommodation predicts that trait covariance originates via a novel developmental input caused by genetic change in one trait, but not the other. Darwin provided a striking example of this process in the ‘lop‐eared’ rabbit by demonstrating that artificial selection for long external ears induced variation in the external auditory meatus. Although this intriguing pattern has been interpreted as evidence of phenotypic accommodation, it is unclear whether it exists and, if it does, whether it is selectively maintained in nature. To address this concern, we examined trait covariance in natural woodrat populations that have likely undergone selection for long ears. We demonstrated a remarkably similar covariance pattern as in the ‘lop‐eared’ rabbit, which was associated with climatic variables along a steep arid‐to‐moist longitudinal gradient. Thus, our results suggest that trait covariance is likely a correlated response to selection. We relate these findings to potential origins of trait covariance owing to altered developmental interactions, such as in phenotypic accommodation. Additional evidence is needed to clarify how phenotypic accommodation and correlated selection promote and maintain trait covariance in natural populations. Nonetheless, our study is the first to support a classic Darwinian example concerning domestication and natural selection.     

Fifty years of co‐evolution and beyond: integrating co‐evolution from molecules to species

Fifty years after Ehrlich and Raven's seminal paper, the idea of co‐evolution continues to grow as a key concept in our understanding of organic evolution. This concept has not only provided a compelling synthesis between evolutionary biology and community ecology, but has also inspired research that extends beyond its original scope. In this article, we identify unresolved questions about the co‐evolutionary process and advocate for the integration of co‐evolutionary research from molecular to interspecific interactions. We address two basic questions: (i) What is co‐evolution and how common is it? (ii) What is the unit of co‐evolution? Both questions aim to explore the heart of the co‐evolutionary process. Despite the claim that co‐evolution is ubiquitous, we argue that there is in fact little evidence to support the view that reciprocal natural selection and coadaptation are common in nature. We also challenge the traditional view that co‐evolution only occurs between traits of interacting species. Co‐evolution has the potential to explain evolutionary processes and patterns that result from intra‐ and intermolecular biochemical interactions within cells, intergenomic interactions (e.g. nuclear‐cytoplasmic) within species, as well as intergenomic interactions mediated by phenotypic traits between species. Research that bridges across these levels of organization will help to advance our understanding of the importance of the co‐evolutionary processes in shaping the diversity of life on Earth.     

The interaction between developmental bias and natural selection: from centipede segments to a general hypothesis

Do limitations to the ways in which mutations can alter developmental processes help to determine the direction of phenotypic evolution? In the early days of neo-Darwinism, the answer given to this question was an emphatic 'no'. However, recent work, both theoretical and empirical, argues that the answer should at least be 'sometimes', and possibly even a straightforward 'yes'. Here, I examine the key concept of developmental bias, which encompasses both developmental constraint and developmental drive. I review the case of centipede segment number, which is a particularly clear example of developmental bias, but also a rather unusual one. I then consider how, in general terms, developmental bias and natural selection might interact, with the result that it is their interaction, rather than either process on its own, that determines evolutionary direction. Essentially, the whole argument is about the extent to which phenotypic variation is developmentally structured as opposed to amorphous or random. This issue can be traced back to the very beginning of evolutionary biology, and in particular to a difference of opinion between Darwin and Wallace, who emphasized, respectively, character correlation and character independence.     

THE LOCI OF REPEATED EVOLUTION: A CATALOG OF GENETIC HOTSPOTS OF PHENOTYPIC VARIATION

What is the nature of the genetic changes underlying phenotypic evolution? We have catalogued 1008 alleles described in the literature that cause phenotypic differences among animals, plants, and yeasts. Surprisingly, evolution of similar traits in distinct lineages often involves mutations in the same gene (“gene reuse”). This compilation yields three important qualitative implications about repeated evolution. First, the apparent evolution of similar traits by gene reuse can be traced back to two alternatives, either several independent causative mutations or a single original mutational event followed by sorting processes. Second, hotspots of evolution—defined as the repeated occurrence of de novo mutations at orthologous loci and causing similar phenotypic variation—are omnipresent in the literature with more than 100 examples covering various levels of analysis, including numerous gain‐of‐function events. Finally, several alleles of large effect have been shown to result from the aggregation of multiple small‐effect mutations at the same hotspot locus, thus reconciling micromutationist theories of adaptation with the empirical observation of large‐effect variants. Although data heterogeneity and experimental biases prevented us from extracting quantitative trends, our synthesis highlights the existence of genetic paths of least resistance leading to viable evolutionary change.     

THE LOCI OF EVOLUTION: HOW PREDICTABLE IS GENETIC EVOLUTION?

Is genetic evolution predictable? Evolutionary developmental biologists have argued that, at least for morphological traits, the answer is a resounding yes. Most mutations causing morphological variation are expected to reside in the cis‐regulatory, rather than the coding, regions of developmental genes. This “cis‐regulatory hypothesis” has recently come under attack. In this review, we first describe and critique the arguments that have been proposed in support of the cis‐regulatory hypothesis. We then test the empirical support for the cis‐regulatory hypothesis with a comprehensive survey of mutations responsible for phenotypic evolution in multicellular organisms. Cis‐regulatory mutations currently represent approximately 22% of 331 identified genetic changes although the number of cis‐regulatory changes published annually is rapidly increasing. Above the species level, cis‐regulatory mutations altering morphology are more common than coding changes. Also, above the species level cis‐regulatory mutations predominate for genes not involved in terminal differentiation. These patterns imply that the simple question “Do coding or cis‐regulatory mutations cause more phenotypic evolution?” hides more interesting phenomena. Evolution in different kinds of populations and over different durations may result in selection of different kinds of mutations. Predicting the genetic basis of evolution requires a comprehensive synthesis of molecular developmental biology and population genetics.     

A spectrum of pleiotropic consequences in development due to changes in a regulatory pathway

Regulatory evolution has frequently been proposed as the primary mechanism driving morphological evolution. This is because regulatory changes may be less likely to cause deleterious pleiotropic effects than changes in protein structure, and consequently have a higher likelihood to be beneficial. We examined the potential for mutations in trans acting regulatory elements to drive phenotypic change, and the predictability of such change. We approach these questions by the study of the phenotypic scope and size of controlled alteration in the developmental network of the bacterium Myxococcus xanthus. We perturbed the expression of a key regulatory gene (fruA) by constructing independent in-frame deletions of four trans acting regulatory loci that modify its expression. While mutants retained developmental capability, the deletions caused changes in the expression of fruA and a dramatic shortening of time required for completion of development. We found phenotypic changes in the majority of traits measured, indicating pleiotropic effects of changes in regulation. The magnitude of the change for different traits was variable but the extent of differences between the mutants and parental type were consistent with changes in fruA expression. We conclude that changes in the expression of essential regulatory regions of developmental networks may simultaneously lead to modest as well as dramatic morphological changes upon which selection may subsequently act.     

生物进化研究的回顾与展望

生物进化是自然科学的永恒之迷。随着历史的发展和科学的进步,生物进化思想从早期的萌芽,到自然选择学说、新达尔文主义,从现代综合理论,到分子进化的中性学说。再到新灾变论和点断平衡论等。当前,由于生物学各分支学科的飞速发展．它们就各自的研究对象在宏观和微观上不断地拓展和深入,并在不同的层次上形成了广泛的交叉、渗透和融合,现代的进化生物学研究从宏观的表型到微观的分子,从群体遗传改变的微进化到成种事件以及地史上生物类群谱系演化的宏进化,从直接的化石证据到基于形态性状、分子证据和环境变迁的综合推理,从基于遗传基础的比较基因组学到演化机理的进化发育生物学等。可以预见,在新的世纪里,在哲学和具体方法论(如系统论、控制论和信息论)的指导下,在生命科学、其他自然科学乃至社会科学工作者的通力合作下,综合遗传、发育和进化等研究领域的各种理论成果,生物进化理论即将出现也一定会出现的一个新的大综合和新的大统一。     

Finalism in Darwinian and Lamarckian Evolution: Lessons from Epigenetics and Developmental Biology

Finalist (teleological) implications have been described for both Darwinian and Lamarckian theories, even though finalism appears to be more commonly associated with Lamarckism. Biologists have focused on finding final causes to explain evolutionary novelties through, for example, applying the ??what for??? question to address experimental observations. Now epigenetics, together with developmental biology, may allow us to focus on the efficient causes leading to evolutionary change, asking the ??how??? question, considering environmental influences as inducers of genomic change. This is a whole under-studied dimension in evolutionary studies. In this paper, I discuss how epigenetics and developmental biology can help integrate two important ways in which the environment affects evolution: through inducing or through restricting the emergence of new phenotypes. I also discuss which aspects of both theories should be reconsidered in the face of current knowledge in epigenetics and where the emphasis of evolutionary experiments should be placed. Important goals of evolution related epigenetic studies should be: (i) to experimentally consider the separation among the origin of characters in a lineage and its further fixation, in order to address these processes in a proper dimension, (ii) to build the cause-effect relation between the factors inducing epigenetic changes and consequent changes in population parameters, and (iii) to consider that the arising of new characters is modulated by physiological and developmental constraints, and that this process is not related to a purpose or focused to solve an ecological, physiological or evolutionary challenge.     

Extending and expanding the Darwinian synthesis: the role of complex systems dynamics

Darwinism is defined here as an evolving research tradition based upon the concepts of natural selection acting upon heritable variation articulated via background assumptions about systems dynamics. Darwin's theory of evolution was developed within a context of the background assumptions of Newtonian systems dynamics. The Modern Evolutionary Synthesis, or neo-Darwinism, successfully joined Darwinian selection and Mendelian genetics by developing population genetics informed by background assumptions of Boltzmannian systems dynamics. Currently the Darwinian Research Tradition is changing as it incorporates new information and ideas from molecular biology, paleontology, developmental biology, and systems ecology. This putative expanded and extended synthesis is most perspicuously deployed using background assumptions from complex systems dynamics. Such attempts seek to not only broaden the range of phenomena encompassed by the Darwinian Research Tradition, such as neutral molecular evolution, punctuated equilibrium, as well as developmental biology, and systems ecology more generally, but to also address issues of the emergence of evolutionary novelties as well as of life itself.     

Diverse phenotypic and genetic responses to short‐term selection in evolving Escherichia coli populations

Beneficial mutations fuel adaptation by altering phenotypes that enhance the fit of organisms to their environment. However, the phenotypic effects of mutations often depend on ecological context, making the distribution of effects across multiple environments essential to understanding the true nature of beneficial mutations. Studies that address both the genetic basis and ecological consequences of adaptive mutations remain rare. Here, we characterize the direct and pleiotropic fitness effects of a collection of 21 first‐step beneficial mutants derived from naïve and adapted genotypes used in a long‐term experimental evolution of Escherichia coli. Whole‐genome sequencing was able to identify the majority of beneficial mutations. In contrast to previous studies, we find diverse fitness effects of mutations selected in a simple environment and few cases of genetic parallelism. The pleiotropic effects of these mutations were predominantly positive but some mutants were highly antagonistic in alternative environments. Further, the fitness effects of mutations derived from the adapted genotypes were dramatically reduced in nearly all environments. These findings suggest that many beneficial variants are accessible from a single point on the fitness landscape, and the fixation of alternative beneficial mutations may have dramatic consequences for niche breadth reduction via metabolic erosion.     

Why don't zebras have machine guns? Adaptation, selection, and constraints in evolutionary theory

In an influential paper, Stephen Jay Gould and Richard Lewontin (1979) contrasted selection-driven adaptation with phylogenetic, architectural, and developmental constraints as distinct causes of phenotypic evolution. In subsequent publications Gould (e.g., 1997a,b, 2002) has elaborated this distinction into one between a narrow "Darwinian Fundamentalist" emphasis on "external functionalist" processes, and a more inclusive "pluralist" emphasis on "internal structuralist" principles. Although theoretical integration of functionalist and structuralist explanations is the ultimate aim, natural selection and internal constraints are treated as distinct causes of evolutionary change. This distinction is now routinely taken for granted in the literature in evolutionary biology. I argue that this distinction is problematic because the effects attributed to non-selective constraints are more parsimoniously explained as the ordinary effects of selection itself. Although it may still be a useful shorthand to speak of phylogenetic, architectural, and developmental constraints on phenotypic evolution, it is important to understand that such "constraints" do not constitute an alternative set of causes of evolutionary change. The result of this analysis is a clearer understanding of the relationship between adaptation, selection and constraints as explanatory concepts in evolutionary theory.     

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.     

Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution

Biologists have long sought to understand which genes and what kinds of changes in their sequences are responsible for the evolution of morphological diversity. Here, I outline eight principles derived from molecular and evolutionary developmental biology and review recent studies of species divergence that have led to a genetic theory of morphological evolution, which states that (1) form evolves largely by altering the expression of functionally conserved proteins, and (2) such changes largely occur through mutations in the cis-regulatory sequences of pleiotropic developmental regulatory loci and of the target genes within the vast networks they control.     

Tinker where the tinkering's good

Do general principles govern the genetic causes of phenotypic evolution? One promising idea is that mutations in cis-regulatory regions play a predominant role in phenotypic evolution because they can alter gene activity without causing pleiotropic effects. Recent evidence that revealed the genetic basis of pigmentation pattern evolution in Drosophila santomea supports this notion. Multiple mutations that disrupt an abdominal enhancer of the pleiotropic gene tan partly explain the reduced pigmentation observed in this species.