Plasticity in the timing of physiological development: physiological heterokairy--what is it, how frequent is it, and does it matter?

The study of developmental sequences of physiological traits could be an important way of placing comparative developmental physiology (CDP) within the research agenda being forged by work on developmental plasticity. Here we focus on the concept of heterokairy defined by Spicer & Burggren in 2003 as changes in the timing of physiological development in an individual. The role of this concept in the future of the CDP is discussed. First we provide an historical perspective of the ideas that have led to the investigation of sequences in CDP. This is followed by a re-examination and clarification of the definition of physiological heterokairy before empirical case studies that (explicitly or implicitly) demonstrate physiological heterokairy are reviewed. We suggest that physiological heterokairy can be demonstrated through a wide range of invertebrate and vertebrate examples. However, care must be taken when inferring that heterokairy as a pattern is always the result of heterokairic processes as there is evidence that physiological heterokairy could result from the altered timing of both homologous or analogous physiological mechanisms. We conclude by discussing the potential link between heterokairy and heterochrony and suggest that the investigation of this link should be a major goal for workers in both CDP and developmental plasticity.     

Plasticity in the timing of physiological development: Physiological heterokairy — What is it, how frequent is it, and does it matter?

The study of developmental sequences of physiological traits could be an important way of placing comparative developmental physiology (CDP) within the research agenda being forged by work on developmental plasticity. Here we focus on the concept of heterokairy defined by Spicer & Burggren in 2003 as changes in the timing of physiological development in an individual. The role of this concept in the future of the CDP is discussed. First we provide an historical perspective of the ideas that have led to the investigation of sequences in CDP. This is followed by a re-examination and clarification of the definition of physiological heterokairy before empirical case studies that (explicitly or implicitly) demonstrate physiological heterokairy are reviewed. We suggest that physiological heterokairy can be demonstrated through a wide range of invertebrate and vertebrate examples. However, care must be taken when inferring that heterokairy as a pattern is always the result of heterokairic processes as there is evidence that physiological heterokairy could result from the altered timing of both homologous or analogous physiological mechanisms. We conclude by discussing the potential link between heterokairy and heterochrony and suggest that the investigation of this link should be a major goal for workers in both CDP and developmental plasticity.     

Analyzing evolutionary patterns in amniote embryonic development

Heterochrony (differences in developmental timing between species) is a major mechanism of evolutionary change. However, the dynamic nature of development and the lack of a universal time frame makes heterochrony difficult to analyze. This has important repercussions in any developmental study that compares patterns of morphogenesis and gene expression across species. We describe a method that makes it possible to quantify timing shifts in embryonic development and to map their evolutionary history. By removing a direct dependence on traditional staging series, through the use of a relative time frame, it allows the analysis of developmental sequences across species boundaries. Applying our method to published data on vertebrate development, we identified clear patterns of heterochrony. For example, an early onset of various heart characters occurs throughout amniote evolution. This suggests that advanced (precocious) heart development arose in evolutionary history before endothermy. Our approach can be adapted to analyze other forms of comparative dynamic data, including patterns of developmental gene expression.     

Dispelling dog dogma: an investigation of heterochrony in dogs using 3D geometric morphometric analysis of skull shape

Heterochrony is an evolutionary mechanism that generates diversity via perturbations of the rate or timing of development that requires very little genetic innovation. As such, heterochrony is thought to be a common evolutionary mechanism in the generation of diversity. Previous research has suggested that dogs evolved via heterochrony and are paedomorphic wolves. This study uses three-dimensional landmark-based coordinate data to investigate heterochronic patterns within the skull morphology of the domestic dog. A total of 677 adult dogs representing 106 different breeds were measured and compared with an ontogenetic series of 401 wolves. Geometric morphometric analysis reveals that the cranial shape of none of the modern breeds of dogs resembles the cranial shapes of adult or juvenile wolves. In addition, investigations of regional heterochrony in the face and neurocranium also reject the hypothesis of heterochrony. Throughout wolf cranial development the position of the face and the neurocranium remain in the same plane. Dogs, however, have a de novo cranial flexion in which the palate is tilted dorsally in brachycephalic and mesaticephalic breeds or tilted ventrally in dolichocephalic and down-face breeds. Dogs have evolved very rapidly into an incredibly morphologically diverse species with very little genetic variation. However, the genetic alterations to dog cranial development that have produced this vast range of phylogenetically novel skull shapes do not coincide with the expectations of the heterochronic model. Dogs are not paedomorphic wolves.     

Using heterochrony plots to detect the dissociated coevolution of characters

The comparison of developmental sequences among species is notoriously difficult. Here, heterochrony plots are introduced as a new graphic method to detect temporal shifts in the development of characters in pair-wise species comparisons. Plotting the timing of character development in one species against the timing of character development in another species allows us to compare a principally unlimited number of characters simultaneously and can detect whether suites of characters are dissociated from one another or not. Such heterochrony plots can be embedded into a comparative phylogenetic analysis in order to establish whether observed patterns of character codissociation are indeed due to their dissociated coevolution. Comparative phylogenetic analysis may also reveal multiple independent events of dissociated coevolution of the same suite of characters in a certain lineage, suggesting that the characters of this suite reciprocally constrain their evolutionary modifiability, thereby forming a unit of evolution. This ability to identify units of evolution is a prerequisite for assessing the validity of recently proposed scenarios, suggesting that modules of development and/or function tend to act as units of evolution. Starting from a detailed heterochrony plot comparing development in the direct developing frog Eleutherodactylus coqui and in the biphasically developing frog Discoglossus pictus, this comparative approach is illustrated focusing on the evolution of development of limbs, the nervous system and the pharyngeal arches in amphibians.     

Physiological and metabolic aspects of experimental heterochrony in colonial hydroids

Hydractiniid hydroids display a range of morphological variation from sheet-like to runner-like forms, thus exemplifying the patterns of heterochrony found in many colonial animals. Experimental studies of clonal replicates of a Podocoryne carnea colony demonstrate a relationship between these heterochronic traits and physiological and metabolic factors. While colonies exposed to dilute solutions of 2, 4-dinitrophenol (an uncoupler of oxidative phosphorylation) for 4 hours per day show a strong dose-response relationship between within-colony gastrovascular flow rate and the timing of morphological development, colonies exposed for 20 hours per day fail to show this relationship. Spectrofluorometric measures of redox state suggest that the degree of “loose-coupling” of oxidative phosphorylation is proportional to the exposure time. Thus colonies exposed for 20 hours have significantly diminished ATP production relative to colonies exposed for 4 hours. Two underlying factors may be responsible for the breakdown of the dose-response relationship between flow rate and development: (1) colonies exposed to a high dose of uncoupler for 20 hours per day allocate a larger-than-normal share of their total energy budget into maintaining the minimal flow rate required physiologically, and (2) colonies' redox state has a direct effect on the timing of morphological development. The latter effect is particularly intriguing, given the extensive literature relating “metabolic activity” to development. In general, these results suggest a relationship between energy allocation, metabolism, and development in these hydroids, and these interrelationships may be central to the evolutionary process of heterochrony.     

Is Sequence Heterochrony an Important Evolutionary Mechanism in Mammals?

It is postulated widely that changes in developmental timing (i.e., heterochrony) represent a major mechanism of evolutionary change. However, it is only with recent methodological advances that changes in the order in which development proceeds (sequence heterochrony) can be identified and quantified. We apply these techniques to examine whether heterochrony in the early embryonic (organogenetic) period has played an important role in the diversification of mammals. Although we find clear instances of sequence heterochrony in mammals, particularly between eutherians and marsupials, the majority of mammalian lineages that we could examine (those within the major clades Euarchontoglires and Laurasiatheria) show few or no heterochronic changes in the 116 events examined (e.g., Artiodactyla, Euarchonta, Fereuungulata, Glires, Primates, Rodentia). This is in contrast with the timing shifts reported between and within other tetrapod clades. Our results suggest that sequence heterochrony in embryonic stages has not been a major feature of mammalian evolution. This might be because mammals, and perhaps amniotes in general, develop for an extended time in a protected environment, which could shield the embryos from strong diversifying selection. Our results are also consistent with the view that mammal embryos are subject to special developmental constraints. Therefore, other mechanisms explaining the diversity of extant mammals must be sought.     

Spatiotemporal reorganization of growth rates in the evolution of ontogeny

Abstract. Heterochrony, evolutionary changes in rate or timing of development producing parallelism between ontogeny and phylogeny, is viewed as the most common type of evolutionary change in development. Alternative hypotheses such as heterotopy, evolutionary change in the spatial patterning of development, are rarely entertained. We examine the evidence for heterochrony and heterotopy in the evolution of body shape in two clades of piranhas. One of these is the sole case of heterochrony previously reported in the group; the others were previously interpreted as cases of heterotopy. To compare ontogenies of shape, we computed ontogenetic trajectories of shape by multivariate regression of geometric shape variables (i.e., partial warp scores and shape coordinates) on centroid size. Rates of development relative to developmental age and angles between the trajectories were compared statistically. We found a significant difference in developmental rate between species of Serrasalmus , suggesting that heterochrony is a partial explanation for the evolution of body shape, but we also found a significant difference between their ontogenetic transformations; the direction of the difference between them suggests that heterotopy also plays a role in this group. In Pygocentrus we found no difference in developmental rate among species, but we did find a difference in the ontogenies, suggesting that heterotopy, but not heterochrony, is the developmental basis for shape diversification in this group. The prevalence of heterotopy as a source of evolutionary novelty remains largely unexplored and will not become clear until the search for developmental explanations looks beyond heterochrony.     

Of coiled oysters and big brains: how to rescue the terminology of heterochrony, now gone astray

SUMMARY During the past decade, the terminology of heterochrony, heretofore consistent and workable, has become internally illogical and incoherent as the unfortunate result of an extension of terms, properly devised to describe shifts in developmental timing of shapes and features, to the rates and timings that cause these shifts. All the resulting, and extensive, confusion in the literature arises as a pure consequence of this error in logic and nomenclature, and not at all from disagreement about the important empirical questions described by this central concept and phenomenon in the integration of evolution and development. In particular, the claim that the same feature in human evolution (the paedomorphic shape of the human cranium) expresses either neoteny or the apparently opposite phenomenon of hypermorphosis only records the terminological error, and not any factual disagreement—for this neotenic feature has probably arisen by a prolongation of juvenile growth patterns inappropriately designated as "hypermorphosis of rate." I show that a prominent and unchallenged case of neoteny in fossil oysters arises by exactly the same evolutionary mode. When we restore the terminology of heterochrony by the "paedomorphic" intellectual event of dropping these inadaptive terminal accretions (the illogical extension of shape categories to describe rates), then the concept of heterochrony will again make proper distinctions by designating a clearly meaningful category of evolutionary changes originating by shifts in timing for features already present in ancestors. "It's not all heterochrony"—and this particular statement of "less is more" represents heterochrony's strength as an interesting subset with definite meaning, rather than an illogical hodge-podge apparently applicable to all phenomena, and therefore explaining nothing.     

A genetic basis for intraspecific differences in developmental timing?

Heterochrony, altered developmental timing between ancestors and their descendents, has been proposed as a pervasive evolutionary feature and recent analytical approaches have confirmed its existence as an evolutionary pattern. Yet, the mechanistic basis for heterochrony remains unclear and, in particular, whether intraspecific variation in the timing of developmental events generates, or has the potential to generate, future between‐species differences. Here we make a key step in linking heterochrony at the inter‐ and intraspecific level by reporting an association between interindividual variation in both the absolute and relative timing (position within the sequence of developmental events) of key embryonic developmental events and genetic distance for the pond snail, Radix balthica. We report significant differences in the genetic distance of individuals exhibiting different levels of dissimilarity in their absolute and relative timing of developmental events such as spinning activity, eyespot formation, heart ontogeny, and hatching. This relationship between genetic and developmental dissimilarity is consistent with there being a genetic basis for variation in developmental timing and so suggests that intraspecific heterochrony could provide the raw material for natural selection to produce speciation.     

Time's arrow: heterochrony and the evolution of development

The concept of heterochrony, which denotes a change in the relative timing of developmental events and processes in evolution, has accompanied attempts to link evolution and development for well over a century. During this time the definition of heterochrony and the application of the concept have varied and by the late 1990's, many questioned the usefulness of the concept. However, in the past decade studies of heterochrony have been revitalized by a new focus on developmental sequence, an examination of heterochrony in explicit phylogenetic contexts and increasing tendencies to examine the heterochrony of many kinds of events, including cellular, molecular and genetic events. Examples of such studies are reviewed in this paper and it is argued that this new application of heterochrony provides an extraordinarily rich opportunity for understanding the developmental basis of evolutionary change.     

Heterochrony and allometry: the analysis of evolutionary change in ontogeny

The connection between development and evolution has become the focus of an increasing amount of research in recent years, and heterochrony has long been a key concept in this relation. Heterochrony is defined as evolutionary change in rates and timing of developmental processes; the dimension of time is therefore an essential part in studies of heterochrony. Over the past two decades, evolutionary biologists have used several methodological frameworks to analyse heterochrony, which differ substantially in the way they characterize evolutionary changes in ontogenies and in the resulting classification, although they mostly use the same terms. This review examines how these methods compare ancestral and descendant ontogenies, emphasizing their differences and the potential for contradictory results from analyses using different frameworks. One of the two principal methods uses a clock as a graphical display for comparisons of size, shape and age at a particular ontogenic stage, whereas the other characterizes a developmental process by its time of onset, rate, and time of cessation. The literature on human heterochrony provides particularly clear examples of how these differences produce apparent contradictions when applied to the same problem. Developmental biologists recently have extended the concept of heterochrony to the earliest stages of development and have applied it at the cellular and molecular scale. This extension brought considerations of developmental mechanisms and genetics into the study of heterochrony, which previously was based primarily on phenomenological characterizations of morphological change in ontogeny. Allometry is the pattern of covariation among several morphological traits or between measures of size and shape; unlike heterochrony, allometry does not deal with time explicitly. Two main approaches to the study of allometry are distinguished, which differ in the way they characterize organismal form. One approach defines shape as proportions among measurements, based on considerations of geometric similarity, whereas the other focuses on the covariation among measurements in ontogeny and evolution. Both are related conceptually and through the use of similar algebra. In addition, there are close connections between heterochrony and changes in allometric growth trajectories, although there is no one-to-one correspondence. These relationships and outline links between different analytical frameworks are discussed.     

Ontogeny and phylogeny of the trunk lateral line system in cichlid fishes

An examination of the ontogeny of the lateral line trunk canal and the diversity of adult trunk canal patterns among cichlids indicates that bidirectional canal formation is a general ontogenetic pattern in the Cichlidae with the exception of Cichla and those few species with a complete trunk canal pattern. In addition to the tubed scales which make up the trunk canal, some lateral line scales have pits containing superficial neuromasts. These are recognized as components of the lateral line system of the trunk in adult cichlids for the first time. Eight trunk canal patterns that are variations on a simple disjunct pattern are defined among the 17 cichlid genera examined. Using bidirectional canal formation as a developmental model, these patterns can be placed along an ontogenetic spectrum. This suggests that heterochrony (alterations in the timing of development) is an important mechanism of evolutionary change in the lateral line system of the trunk in cichlid fishes.     

Functional evolutionary developmental biology (evo-devo) of morphological novelties in plants

The origin of morphological and ecological novelties is a long-standing problem in evolutionary biology.Understanding these processes requires investigation from both the development and evolution standpoints,which promotes a new research field called evolutionary developmental biology (evo-devo).The fundamental mechanism for the origin of a novel structure may involve heterotopy,heterochrony,ectopic expression,or loss of an existing regulatory factor.Accordingly,the morphological and ecological traits cont...     

Heterochrony in plant evolutionary studies through the twentieth century

The evolution of plant morphology is the result of changes in developmental processes. Heterochrony, the evolutionary change in developmental rate or timing, is a major cause of ontogenetic modification during evolution. It is responsible for both interspecific and intraspecific morphological differences. Other causes include heterotopy, the change of structural position, and homeosis, the replacement of a structure by another. This paper discusses and reviews the role of heterochrony in plant evolution at the organismal, organ, tissue, cellular, and molecular levels, as well as the relationships among heterochrony, heterotopy, and homeosis. An attempt has been made to include all published studies through late 1999. It is likely that most heterochronic change involves more than one of the six classic pure heterochronic processes. Of these processes, we found neoteny (decreased developmental rate in descendant), progenesis (earlier offset), and acceleration (increased rate) to be more commonly reported than hypermorphosis (delayed offset) or predisplacement (earlier onset). We found no reports of postdisplacement (delayed onset). Therefore, although rate changes are common (both neoteny and acceleration), shifts in timing most commonly involve earlier termination in the descendant (progenesis). These relative frequencies may change as more kinds of structures are analyzed. Phenotypic effects of evolutionary changes in onset or offset timing can be exaggerated, suppressed, or reversed by changes in rate. Because not all developmental changes responsible for evolution result from heterochrony, however, we propose that plant evolution be studied from a viewpoint that integrates these different developmental mechanisms.     

Physiological regulatory networks: ecological roles and evolutionary constraints

Ecological and evolutionary physiology has traditionally focused on one aspect of physiology at a time. Here, we discuss the implications of considering physiological regulatory networks (PRNs) as integrated wholes, a perspective that reveals novel roles for physiology in organismal ecology and evolution. For example, evolutionary response to changes in resource abundance might be constrained by the role of dietary micronutrients in immune response regulation, given a particular pathogen environment. Because many physiological components impact more than one process, organismal homeostasis is maintained, individual fitness is determined and evolutionary change is constrained (or facilitated) by interactions within PRNs. We discuss how PRN structure and its system-level properties could determine both individual performance and patterns of physiological evolution.     

Synchrony and heterochrony in ontogeny (of fish)

The ontogeny of an organism is a complex process that strongly depends on the timing of developmental processes. In this article, I discuss ontogeny of fish (and other organisms) in temporal terms, based on the hypothesis that organisms as self-organized entities may create their own times for their development, and that this development consists of a sequence of longer stabilized states (steps) with shorter, intermittent less-stable intervals (thresholds). If viewed within the context of structure-to-structure, organ-to-organ and/or organism-to-environment relationships, then the saltatory pattern of ontogeny emerges at each transition from one stabilized state to another. I consider two timing mechanisms essential to ontogeny - synchrony (coordinating) and heterochrony (implementing); their possible roles are discussed. Besides this, a new context and understanding for the term heterochrony is proposed. At least three levels of heterochrony should be distinguished: interspecific, intraspecific and intraindividual. However, the difference among these three types of heterochrony is not in the phenomenon itself but in the way we perceive and classify it.     

Environmentally cued hatching across taxa: embryos respond to risk and opportunity

Most animals begin life in eggs, protected and constrained by a capsule, shell, or other barrier. As embryos develop, their needs and abilities change, altering the costs and benefits of encapsulation, and the risks and opportunities of the outside world. When the cost/benefit ratio is better outside the egg, animals should hatch. Adaptive timing of hatching evolves in this context. However, many environmental variables affect the optimal timing of hatching so there is often no consistent best time. Across a broad range of animals, from flatworms and snails to frogs and birds, embryos hatch at different times or at different developmental stages in response to changing risks or opportunities. Embryos respond to many types of cues, assessed via different sensory modalities. Some responses appear simple. Others are surprisingly complex and sophisticated. Parents also manipulate the timing of hatching. The number and breadth of examples of cued hatching suggest that, in the absence of specific information, we should not assume that hatching timing is fixed. Our challenge now is to integrate information on the timing of hatching across taxa to better understand the diversity of patterns and how they are structured in relation to different types of environmental and developmental variation. As starting points for comparative studies, I: (1) suggest a framework based on heterokairy-individual, plastic variation in the rate, timing, or sequence of developmental events and processes-to describe patterns and mechanisms of variation in the timing of hatching; (2) briefly review the distribution of environmentally cued hatching across the three major clades of Bilateria, highlighting the diverse environmental factors and mechanisms involved; and (3) discuss factors that shape the diversity of plastic and fixed timing of hatching, drawing on evolutionary theory on phenotypic plasticity which directs our attention to fitness trade-offs, environmental heterogeneity, and predictive cues. Combining mechanistic and evolutionary perspectives is necessary because development changes organismal interactions with the environment. Integrative and comparative studies of the timing of hatching will improve our understanding of embryos as both evolving and developing organisms.