No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Integration and the Developmental Genetics of Allometry
Abstract
Allometry refers to the ways in which organismal shape is associated with size. It is a special case of integration, or the tendency for traits to covary, in that variation in size is ubiquitous and evolutionarily important. Allometric variation is so commonly observed that it is routinely removed from morphometric analyses or invoked as an explanation for evolutionary change. In this case, familiarity is mistaken for understanding because rarely do we know the mechanisms by which shape correlates with size or understand their significance. As with other forms of integration, allometric variation is generated by variation in developmental processes that affect multiple traits, resulting in patterns of covariation. Given this perspective, we can dissect the genetic and developmental determinants of allometric variation. Our work on the developmental and genetic basis for allometric variation in craniofacial shape in mice and humans has revealed that allometric variation is highly polygenic. Different measures of size are associated with distinct but overlapping patterns of allometric variation. These patterns converge in part on a common genetic basis. Finally, environmental modulation of size often generates variation along allometric trajectories, but the timing of genetic and environmental perturbations can produce deviations from allometric patterns when traits are differentially sensitive over developmental time. These results question the validity of viewing allometry as a singular phenomenon distinct from morphological integration more generally.
... Although it lacks the 3D approach of GMM, the use of linear distances showed on several instances that large cranial regions display different allometries relative to the entire skull (Slijper, 1962;Monteiro et al., 1999;Ross & Metzger, 2004;Marroig & Cheverud, 2004). These studies have highlighted complex allometric trends on the mammalian skull, which are likely determined by multiple and interacting developmental processes (Hallgrímsson et al., 2019). In fact, much remains to be discovered about these complex morphological patterns especially in the way that allometric growth differentially affects the various parts of the skull and induces cranial shape changes during ontogeny. ...
... Studies have shown that the size-related changes of traits, called allometry, indeed represent a pervasive pattern in morphological evolution (Gould, 1966;Hallgrímsson et al., 2019). However, the variation of this pattern, within and among species, remains poorly known for many taxa. ...
... Allometric variation may indeed differ between closely related species (e.g., Frost et al., 2003), and thus analyses of size-related shape changes within one species are not sufficient to infer allometric patterns within other species or within an entire clade. Allometry constitutes a complex and highly polygenic phenomenon (Zelditch et al., 2003;Klingenberg, 2010;Pélabon et al., 2014;Hallgrímsson et al., 2019). Various factors (e.g., ecology) may influence size variation and thus indirectly impact morphological variation through allometric processes in several species (e.g., Esquérré et al., 2017). ...
Morphological variation is a complex phenomenon whose use in phylogenetic analyses is often criticized. Many studies have called for a broader exploration of patterns of morphological variation and a better identification of the covariation among traits to improve morphological phylogenetics. Cingulates represent an ideal case study for this objective since they illustrate a typical case of conflict between morphological and molecular phylogenetic reconstructions, especially for the origins of the extinct glyptodonts. In this work, we first highlight this incongruence and point out the existing gaps concerning our knowledge of the internal cranial anatomy and the patterns of integration on the skull of cingulates. An exploration of these two aspects is relevant to the enrichment of morphological matrices and to a better understanding of the existing covariations among characters, which can mislead morphological phylogenetics. Our work starts with an in-depth study of the internal anatomy of the skull (focused on selected canals and cavities related to cranial vascularization, innervation or tooth insertion) in a diverse sample of Cingulata. We tentatively reconstruct the evolutionary scenarios of eight selected traits on these structures. These suggest a greater resemblance of glyptodonts with pampatheres, with the genus Proeutatus and/or with chlamyphorines, which is partly congruent with molecular phylogenies. Then, we explore patterns of cranial integration within several species of extant armadillos and test if the patterns found at the instrapecific level are also supported at the evolutionary level, i.e., among species, using a rich sample of extant and extinct cingulates. We first focus on one of the most powerful integration factors known in mammals - allometry - in order to target cranial covariation patterns related to size variation. Our analysis of cranial allometry enabled us to highlight several cranial allometric patterns that are widespread in cingulates. One of the strongest allometric patterns detected corresponds to the craniofacial allometry (relatively long face in large crania), but strong and widespread allometric changes were also detected for the postorbital constriction, the zygomatic arch, the nuchal crests, the mastoid process of the petrosal, the cranial roof and the foramen magnum. Second, we perform a selective exploration of pairs of strongly covarying distances in the same samples which enable us to highlight additional strong cranial correlations. The correlations supported at both the intraspecific and evolutionary levels concern in particular the anterior root of zygomatic arch, a region particularly rich in muscular insertions. Third, we present the very first exploration of cranial modularity in cingulates at the intraspecific level that reveals a partitioning of the integration into three anteroposteriorly distributed modules on the skull. Our results are finally compared with existing morphological matrices and phylogenetic hypotheses. Although it hints at a necessary revision of several characters, the comparison of the detected patterns of integration with morphological matrices proves difficult. This highlights the necessity to further explore alternative coding strategies for a better evaluation of the covariation and allometry among scored characters and for an overall improvement of our character constructions.
... In chicken and mice, bone formation appears to be dependent on functional muscles that perform embryonic muscle contraction . Third, the extreme snout elongation of myrmecophagous placentals, particularly anteaters, should add increasing amounts of variance in this part of the skull Cardini & Polly, 2013;Cardini, 2019a), somatic growth of bone tissues being one of the main processes contributing to structural covariation on the mammalian skull (Hallgrímsson et al., , 2019Gonzalez et al., 2013). ...
... The structure of these parts of the skull is quite conserved and correspond to those in previously proposed architectures (Cheverud, 1982;). These regions originate from the mesoderm in the very early stages of skull development (e.g., Hallgrímsson et al., 2019). In addition to their common tissue origin, covariance-generating processes such as muscle-bone interaction, tooth eruption, 187 or occlusion (Hallgrímsson et al., , 2019Bookstein & Mitteroecker, 2014) mostly occur anterior to the temporal fossa. ...
... These regions originate from the mesoderm in the very early stages of skull development (e.g., Hallgrímsson et al., 2019). In addition to their common tissue origin, covariance-generating processes such as muscle-bone interaction, tooth eruption, 187 or occlusion (Hallgrímsson et al., , 2019Bookstein & Mitteroecker, 2014) mostly occur anterior to the temporal fossa. ...
The subject of this thesis is the morphological convergence in the skull of ant- and termite-eating placentals. Its goals are to characterize tooth reduction, covariance patterns, and morphological variation of the skull, and explore their link to the selective pressures associated to myrmecophagy.The first chapter focuses on the evolutionary, ontogenetic, and static variations of the skull in pangolins, a group of myrmecophagous animals that include the most threatened mammalian species on Earth. The morphological delimitation between seven of the eight species is demonstrated. Their ontogenetic allometric trajectories are described and the implications of the size variation on systematics are discussed. Additionally, intraspecific variation was partly associated to molecular distinctiveness of recently diverged cryptic species within the white-bellied pangolin. These results were obtained with the use of three-dimensional geometric morphometric methods.The second chapter was dedicated to the comparative anatomy of the mandible and masticatory apparatus. First, I investigate the internal mandibular anatomy on a comparative sample of placental mammals using µ-CT tomography and histology. Structures putatively associated to tooth innervation (dorsal canaliculi) are present in toothless anteaters, while they are absent in pangolins, which are equally toothless. Comparative anatomy performed intra- and interspecifically allowed to: i) show that dorsal canaliculi are invariably present in anteaters; ii) confirm the relationship between dorsal canaliculi and early tooth development; iii) show the independent evolution of dorsal canaliculi in anteaters and toothless whales. Dorsal canaliculi are vascularized and innervated in the collared anteater, despite its tooth loss. This suggests that despite tooth loss, tooth pulp innervation likely maintained its sensorial role on the dorsal part of the mandible of anteaters. The second part of chapter 2 is devoted to the comparative anatomy of the head musculature of the three extant anteater genera. Classical and digital dissections confirmed the reduction of the masticatory apparatus in anteaters. The masticatory apparatus of the pygmy anteater is found to significantly differ from that the other two genera. A comparison with the head musculatures of pangolins and aardvarks was done, based on previously published studies. Despite being myrmecophagous, the head musculature of aardvarks and pangolins shows some key differences from that of anteaters. This suggests that the feeding apparatus of ant- and termite-eating placentals varies at the functional level.The last chapter of this thesis covers the patterns of phenotypic covariance of the skull of 15 myrmecophagous species. A geometric morphometrics approach is used in order to explore and confirm hypotheses of modularity. Results show that patterns of modularity in myrmecophagous mammals resemble those of other placentals mammals. No common shift in the parcellation was found, other than that expected from the null hypothesis. Results suggest instead that skull elongation might have resulted on a slight remodeling of modularity patterns on the rostrum region in myrmecophagid anteaters. A preliminary analysis of ontogenetic trajectories of phenotypic covariance matrices in two myrmecophagous species shows that covariance patterns significantly change during ontogeny. This indicates that functional interpretations of static modularity and integration must be taken with caution.
... For all that allometry exemplifies the simplest of constraints, and can be viewed as the simplest case of morphological integration, allometry itself is not biologically simple (Hallgrimsson et al., 2019). Growth allometry is not simple because it arises from multiple, partially overlapping processes that are related through their common influences on size; thus, growth allometry depends on the relative contributions of those various global and local processes (Hallgrimsson et al., 2019;Larson et al., 2018). ...
... For all that allometry exemplifies the simplest of constraints, and can be viewed as the simplest case of morphological integration, allometry itself is not biologically simple (Hallgrimsson et al., 2019). Growth allometry is not simple because it arises from multiple, partially overlapping processes that are related through their common influences on size; thus, growth allometry depends on the relative contributions of those various global and local processes (Hallgrimsson et al., 2019;Larson et al., 2018). Allometry within a single age class (static allometry) is even more complex because that is determined not only by growth allometry, but also by the covariance between the allometric slope and body size (Pelabon et al., 2013). ...
Allometry has been a paradigm of constraints, including intrinsic constraints on the evolvability of allometry, as a source of developmental and genetic constraints on the evolution of form, and of functional constraints, maintaining functional equivalence as body size evolves. Yet, allometry may be the simplest case of varied constraints, and of morphological integration, even though allometry itself is not simple. Evolutionary allometry may be especially complex because it depends not only on developmental origins of allometry and determinants of allometric variation but also on the evolutionary dynamics of size and shape. It should also depend on the ecological opportunity for size-dependent ecomorphological specialization. We predict that lineages that converge in those would exhibit similar evolutionary allometries but otherwise, evolutionary allometries would be heterogeneous. Countering this expectation are familiar craniofacial evolutionary allometries, often ascribed to developmental bias. To test both those hypotheses, we compare evolutionary allometries of mandibles across lineages of squirrels and evolutionary to growth allometries. As expected, lineages that converge on size-dependent specializations exhibit similar evolutionary allometries, but otherwise their allometries are no more similar than expected by chance. Growth allometries of squirrels (and a cricetid rodent) slightly resemble the evolutionary allometry of one lineage, but growth allometries of species from other lineages are orthogonal to their own lineages’ evolutionary allometry. We would expect that craniofacial allometries that are not brain-driven would, like mandibular evolutionary allometries, be predictable only from size-dependent ecological specializations.
... In addition, recent analyses of variation in the allometric relationship between brain and body size across a variety of mammalian and avian clades have illuminated the macroevolutionary history of encephalization (Ksepka et al., 2020;Smaers et al., 2012;Weisbecker et al., 2021). Regardless of the comparative method used, choosing appropriate measures of both brain size and organismal size is critical for producing valid and interpretable encephalization measures (Hallgrímsson et al., 2019). ...
... interpretations of additive strain encephalization effects within our results. It also confirms that different body size measures can lead to notably different conclusions (see alsoHallgrímsson et al., 2019). ...
Brain and skull tissues interact through molecular signalling and mechanical forces during head development, leading to a strong correlation between the neurocranium and the external brain surface. Therefore, when brain tissue is unavailable, neurocranial endocasts are often used to approximate brain size and shape. Evolutionary changes in brain morphology may have resulted in secondary changes to neurocranial morphology, but the developmental and genetic processes underlying this relationship are not well understood. Using automated phenotyping methods, we quantified the genetic basis of endocast variation across large genetically varied populations of laboratory mice in two ways: (1) to determine the contributions of various genetic factors to neurocranial form and (2) to help clarify whether a neurocranial variation is based on genetic variation that primarily impacts bone development or on genetic variation that primarily impacts brain development, leading to secondary changes in bone morphology. Our results indicate that endocast size is highly heritable and is primarily determined by additive genetic factors. In addition, a non‐additive inbreeding effect led to founder strains with lower neurocranial size, but relatively large brains compared to skull size; suggesting stronger canalization of brain size and/or a general allometric effect. Within an outbred sample of mice, we identified a locus on mouse chromosome 1 that is significantly associated with variation in several positively correlated endocast size measures. Because the protein‐coding genes at this locus have been previously associated with brain development and not with bone development, we propose that genetic variation at this locus leads primarily to variation in brain volume that secondarily leads to changes in neurocranial globularity. We identify a strain‐specific missense mutation within Akt3 that is a strong causal candidate for this genetic effect. Whilst it is not appropriate to generalize our hypothesis for this single locus to all other loci that also contribute to the complex trait of neurocranial skull morphology, our results further reveal the genetic basis of neurocranial variation and highlight the importance of the mechanical influence of brain growth in determining skull morphology. The genetic basis neurocranial size variation was analyzed in inbred and outbred mouse populations, indicating high heritability, with strong additive genetic contributions, as well as significant non‐additive contributions. A chromosome 1 locus encompassing protein‐coding genes of brain development is associated with several size measures, suggesting that genetic variation at this locus leads primarily to variation in brain volume that secondarily leads to changes in skull form.
... Placental mammals repeatedly evolved a wide range of body sizes in their history and span over eight orders of magnitude in size today (Alroy 1998;Baker et al. 2015;Price and Hopkins 2015;Bokma et al. 2016). Allometry, the size-related changes of traits, constitutes a major and pervasive pattern in morphological evolution (Gould 1966;Hallgrímsson et al. 2019), and yet it remains only sporadically documented in placentals. Scaling relationships were probably important along with their diversification in size and impacted several aspects of their skull (Nummela 1995;Cardini and Polly 2013). ...
... While choosing a local measure of size (molar field), we assumed that molar proportions were more closely linked to local processes than to those determining variation in overall body size or size of other organs (Hallgrímsson et al. 2019). Yet, the absolute size of molars is also roughly indicative of body sizes in mammals (e.g., Copes and Schwartz 2010). ...
Iterative segments such as teeth or limbs are a widespread characteristic of living organisms. While their proportions may be governed by similar developmental rules in vertebrates, there is no emerging pattern as regards their relation to size. Placental mammals span eight orders of magnitude in body size and show a wide spectrum of dietary habits associated with size and reflected in their dentitions, especially molars. Although variation in size constitutes an important determinant for variation in biological traits, few major allometric trends have been documented on placental molars so far. Molar proportions have been intensively explored in placentals in relation to developmental models, but often at a small phylogenetic scale. Here, we analyzed the diversity of upper molar proportions in relation to absolute size in a large sample of placental species (n = 286) encompassing most of the group's dental diversity. Our phylogenetically informed analyses revealed a twofold pattern of evolutionary integration among upper molars: while molars covary in size with each other, their proportions covary with the absolute size of the entire molar field. With increasing absolute size, posterior molars increase in size relative to anterior ones, meaning that large-sized species have relatively large rear molars while the opposite is true for small-sized species. The directionality of proportional increase in the molar row exhibits a previously unsuspected allometric patterning among placentals, showing how large-scale variations in size may have influenced variation in dental morphology. This finding provides new evidence that processes regulating the size of individual molars are integrated with overall patterns of growth and calls for further testing of allometric variation in the dentition and in other segmental series of the vertebrate body.
... Although it lacks the 3D approach of GMMs, the use of linear distances in several instances showed that large cranial regions display different allometries relative to the entire skull (Slijper, 1962;Monteiro et al., 1999;Ross & Metzger, 2004;Marroig & Cheverud, 2004). These studies have highlighted complex allometric trends on the mammalian skull, which are probably determined by multiple and interacting developmental processes (Hallgrímsson et al., 2019). In fact, much remains to be discovered about these complex morphological patterns, especially in the way that allometric growth differentially affects the various parts of the skull and induces cranial shape changes during ontogeny. ...
... Slight methodological artefacts (e.g. number of landmarks per object) and the multiplicity of developmental and genetic processes at stake during local cranial morphogenesis (Hallgrímsson et al., 2019) may explain the heterogeneous pattern found in our study. In addition, the proportion of total shape variation of each cranial unit explained by an independent variable, here size, may also depend on how much other variables (e.g. ...
A large part of extant and past mammalian morphological diversity is related to variation in size through allometric effects. Previous studies suggested that craniofacial allometry is the dominant pattern underlying mammalian skull shape variation, but cranial allometries were rarely characterized within cranial units such as individual bones. Here, we used 3D geometric morphometric methods to study allometric patterns of the whole skull (global) and of cranial units (local) in a postnatal developmental series of nine-banded armadillos (Dasypus novemcinctus ssp.). Analyses were conducted at the ontogenetic and static levels, and for successive developmental stages. Our results support craniofacial allometry as the global pattern along with more local allometric trends, such as the relative posterior elongation of the infraorbital canal, the tooth row reduction on the maxillary, and the marked development of nuchal crests on the supraoccipital with increasing skull size. Our study also reports allometric proportions of shape variation varying substantially among cranial units and across ontogenetic stages. The multi-scale approach advocated here allowed unveiling previously unnoticed allometric variations, indicating an untapped complexity of cranial allometric patterns to further explain mammalian morphological evolution.
... [1][2][3] These studies paved the way for many future studies in developmental and evolutionary biology. [4][5][6][7][8][9][10][11][12] The present work is focused on the evolution and development of cellular architecture and in particular the structural connectivity of the human brain. Many of the tools available for study, in sauropsid embryology, [6][7][8][9][10][11][12] are unavailable to the study of the human brain. ...
... [4][5][6][7][8][9][10][11][12] The present work is focused on the evolution and development of cellular architecture and in particular the structural connectivity of the human brain. Many of the tools available for study, in sauropsid embryology, [6][7][8][9][10][11][12] are unavailable to the study of the human brain. The lack of appropriate tools in human neuroscience has precluded our ability to visualize connections and trace cell populations in as much detail in humans as in model organisms. ...
The brain is composed of a complex web of networks but we have yet to map the structural connections of the human brain in detail. Diffusion MR imaging is a high‐throughput method that relies on the principle of diffusion to reconstruct tracts (i.e., pathways) across the brain. Although diffusion MR tractography is an exciting method to explore the structural connectivity of the brain in development and across species, the tractography has at times led to questionable interpretations. There are at present few if any alternative methods to trace structural pathways in the human brain. Given these limitations and the potential of diffusion MR imaging to map the human connectome, it is imperative we develop new approaches to validate neuroimaging techniques. I discuss our recent studies integrating neuroimaging with transcriptional and anatomical variation across humans and other species over the course of development and in adulthood. Developing novel frameworks to harness the potential of diffusion MR tractography provides new and exciting opportunities to study the evolution of developmental mechanisms responsible for variation in connections and bridge the gap between model systems and humans. This article is protected by copyright. All rights reserved.
... This spatially-patterned growth is different in different species, resulting in characteristic differences in wing shape ( Nijhout et al. 2014). The regulatory processes that coordinate systemic hormonal signaling with cell-autonomous growth responses are still a mystery, as also pointed out in the presentation by Hallgr ımsson et al. (2019). Lavine et al. (2019) reported on studies with the Asian rhinoceros beetle, Trypoxylus dichotomus, whose males possess exaggerated head and thoracic horns that have a strongly positive allometry with body size. ...
... It seems reasonable to assume that the cellular and molecular response to various physical forces would be mediated by mechanisms not usually considered when thinking about the control of growth and scaling. Such considerations almost certainly account, at least in part, for some of the puzzling associations between genes and allometries (Hallgr ımsson et al. 2019). Rodriguez and Eberhard (2019) reported on the interaction between sexual selection and static allometry. ...
Until recently, the study of allometry has been mostly descriptive, and consisted of a diversity of methods for fitting regressions to bivariate or multivariate morphometric data. During the past decade, researchers have been developing methods to extract biological information from allometric data that could be used to deduce the underlying mechanisms that gave rise to the allometry. In addition, an increasing effort has gone into understanding the kinetics of growth and the regulatory mechanisms that control growth of the body and its component parts. The study of allometry and scaling has now become an exceptionally diverse field, with different investigators applying state of the art methods and concepts in evolution, developmental biology, cell biology and genetics. Diversity has caused divergence, and we felt that although there is general agreement about the new goals for the study of allometry (understanding underlying mechanisms and how those evolve to produce different morphologies), progress is hindered by lack of coordination among the different approaches. We felt the time was right to bring these diverse practitioners together in a symposium to discuss their most recent work in the hope of forging new functional, conceptual, and collaborative connections among established and novice practitioners.
... Although allometric scaling may be harder to modify than mean trait sizes (Egset et al. 2012;Bolstad et al. 2015;Houle et al. 2019), artificial selection, quantitative genetics, and phylogenetic studies have demonstrated sufficient standing genetic variation to permit changes over short time spans (Wilkinson 1993;Emlen 1996;Baker and Wilkinson 2001;Frankino et al. 2005; Rodr ıguez and Al-Wathiqui 2012; Stillwell et al. 2016;summary Nijhout and McKenna 2017). The likelihood that high numbers of growth parameters are involved in determining the allometric relationships of different structures (Nijhout and McKenna 2017), and the complexity of the mechanisms that determine the allometries of different aspects of any given structure (Hallgrimmsson et al. 2019), both imply that genetic variation on which selection can act is common. Another possible limit to the evolution of functional allometries concerns the possibility that selection in favor of a particular allometric state is spread over many pleiotropic effects (Houle et al. 2019). ...
... The same multiplicity of growth mechanisms just mentioned, the covariance between them (Nijhout and McKenna 2017;Hallgrimmsson et al. 2019), and the apparent general importance of nutrition and insulin in various species (Shingleton et al. 2007;McKenna and Nijhout 2019;Casasa et al. 2019) imply that pleiotropy is common in the variables that control the growth of the types of structures that we have discussed above. Nevertheless, the fact that our results show that sexually selected structures with different functions show the predicted allometric patterns supports the notion that pleiotropic constraints on allometry have not been severe. ...
Sexually-selected traits often show positive static allometry, with large individuals bearing disproportionately large structures. But many other sexually-selected traits show isometry or even negative allometry, with trait size varying relatively little with body size. We recently proposed that the functions of these traits (as aggressive signals, weapons, courtship signals, and contact courtship devices) determine their allometries. Positive allometry is generally favored for aggressive signals, because aggressive signals are selected to emphasize body size (and thus fighting prowess). In contrast, the biomechanics of force application in weapons only sometimes select for positive allometry; the content of courtship signals is even less often related to body size; and contact courtship devices are selected to be relatively invariant across body sizes. Here we summarize the arguments in favor of this "functional allometry" hypothesis and expand a comparative test of its predictions. Our results indicate that sexual traits have the allometric slopes predicted by our hypothesis, regardless of which body part bears the structure.
... We compare the static modularity patterns of Xenopus and Salamandra, testing the hypothesis that they share similar modularity patterns despite having different mandibular morphologies, life cycles and ecologies. Because allometry is sometimes thought to be an important factor influencing trait integration (Bright et al., 2016;Hallgrímsson et al., 2019), we also quantified the strength and significance of allometry on mandibular morphology. Finally, we examine the effects of sex on jaw morphology in Xenopus. ...
Modularity describes the degree to which the components of complex phenotypes vary semi-autonomously due to developmental, genetic and functional correlations. This is a key feature underlying the potential for evolvability, as it can allow individual components to respond to different selective pressures semi-independently. The vertebrate lower jaw has become a model anatomical system for understanding modularity, but to date most of this work has focused on the mandible of mammals and other amniotes. In contrast, modularity in the mandible of lissamphibians has been less well studied. Here, we used geometric morphometrics to quantify the static (intraspecific) modularity patterns in Xenopus laevis and Salamandra salamandra gigliolii. We tested developmental and functional hypotheses of modularity and demonstrate that both species exhibit significant modularity. Functional modularity was supported in both Xenopus and Salamandra. Allometry has a small yet significant impact on lower jaw shape in both taxa and sex has a significant effect on shape in Xenopus. The high lower jaw modularity in both species observed here, combined with the well-established modularity of the amphibian cranium, suggests that modularity is a ubiquitous feature of the tetrapod head.
... CREA alleges that, among closely related species, the smaller-sized of the group would appear paedomorphic, possessing proportionally smaller rostra and larger braincases 14,15 . Morphological evolutionary allometry is a ubiquitous phenotypic phenomenon that can be interpreted as a form of integration (i.e., the tendency of multiple traits to covary throughout a biological structure 16 ; in line with the concept of epigenetic interaction sensu Waddington 17,18 ) and is often maintained by natural selection acting on the genetic and pleiotropic architecture that underlies this evolutionary pattern 19,20 . Because CREA pattern describes the size-shape relationship between different parts of the cranium (i.e., rostrum versus braincase size and shape), the concept is intrinsically linked to that of phenotypic integration 21,22 . ...
Among evolutionary trends shaping phenotypic diversity over macroevolutionary scales, CREA (CRaniofacial Evolutionary Allometry) describes a tendency, among closely related species, for the smaller-sized of the group to have proportionally shorter rostra and larger braincases. Here, we used a phylogenetically broad cranial dataset, 3D geometric morphometrics, and phylogenetic comparative methods to assess the validity and strength of CREA in extinct and living felids. To test for the influence of biomechanical constraints, we quantified the impact of relative canine height on cranial shape evolution. Our results provided support to CREA at the family level. Yet, whereas felines support the rule, big cats, like Pantherinae and Machairodontinae, conform weakly if not at all with CREA predictions. Our findings suggest that Machairodontinae constitute one of the first well-supported exceptions to this biological rule currently known, probably in response to the biomechanical demands and developmental changes linked with their peculiar rostral adaptations. Our results suggest that the acquisition of extreme features concerning biomechanics, evo-devo constraints, and/or ecology is likely to be associated with peculiar patterns of morphological evolution, determining potential exceptions to common biological rules, for instance, by inducing variations in common patterns of evolutionary integration due to heterochronic changes under ratchet-like evolution.
... From our work, for example, we observe that mutations in mice that affect growth at the cranial synchondroses produce very similar patterns of shape change across the mouse skull, even if they involve very dif fer ent mechanisms or even dif fer ent kinds of perturbations to the synchondroses at the cellular level (Parsons et al. 2015). Similarly, mutations that affect overall growth are often associated with similar patterns of allometric change that would count as shared patterns of pleiotropy (Hallgrímsson et al. 2019). ...
Essays on evolvability from the perspectives of quantitative and population genetics, evolutionary developmental biology, systems biology, macroevolution, and the philosophy of science.
Evolvability—the capability of organisms to evolve—wasn't recognized as a fundamental concept in evolutionary theory until 1990. Though there is still some debate as to whether it represents a truly new concept, the essays in this volume emphasize its value in enabling new research programs and facilitating communication among the major disciplines in evolutionary biology. The contributors, many of whom were instrumental in the development of the concept of evolvability, synthesize what we have learned about it over the past thirty years. They focus on the historical and philosophical contexts that influenced the emergence of the concept and suggest ways to develop a common language and theory to drive further evolvability research.
The essays, drawn from a workshop on evolvability hosted in 2019–2020 by the Center of Advanced Study at the Norwegian Academy of Science and Letters, in Oslo, provide scientific and historical background on evolvability. The contributors represent different disciplines of evolutionary biology, including quantitative and population genetics, evolutionary developmental biology, systems biology, and macroevolution, as well as the philosophy of science. This plurality of approaches allows researchers in disciplines as diverse as developmental biology, molecular biology, and systems biology to communicate with those working in mainstream evolutionary biology. The contributors also discuss key questions at the forefront of research on evolvability.
Contributors:J. David Aponte, W. Scott Armbruster, Geir H. Bolstad, Salomé Bourg, Ingo Brigandt, Anne Calof, James M. Cheverud, Josselin Clo, Frietson Galis, Mark Grabowski, Rebecca Green, Benedikt Hallgrímsson, Thomas F. Hansen, Agnes Holstad, David Houle, David Jablonski, Arthur Lander, Arnaud LeRouzic, Alan C. Love, Ralph Marcucio, Michael B. Morrissey, Laura Nuño de la Rosa, Øystein H. Opedal, Mihaela Pavličev, Christophe Pélabon, Jane M. Reid, Heather Richbourg, Jacqueline L. Sztepanacz, Masahito Tsuboi, Cristina Villegas, Marta Vidal-García, Kjetil L. Voje, Andreas Wagner, Günter P. Wagner, Nathan M. Young
... Allometric variation is analyzed because it is generated by variation in developmental processes that affect multiple traits, resulting in overall patterns of covariation, and it contributes to morphological integration and modularity (Klingenberg, 2013;Mitteroecker & Bookstein, 2007;Hallgrímsson et al., 2019). To explore regionalization, we used segmented linear regression (SLR) (Head & Polly, 2015;Jones et al., 2018), which provides information on the most probable changes in the pattern of covariation and suggests possible regions. ...
Serially homologous structures may have complex patterns of regionalization and morphological integration, influenced by developmental Hox gene expression and functional constraints. The vertebral column, consisting of a number of repeated, developmentally constrained, and highly integrated units-vertebrae-is such a complex serially homologous structure. Functional diversification increases regionalization and modularity of the vertebral column, particularly in mammals. For salamanders, three concepts of regionalization of the vertebral column have been proposed, recognizing one, two, or three presacral regions. Using three-dimensional geometric morphometrics on vertebra models acquired with microcomputerized tomography scanning, we explored the covariation of vertebrae in four closely related taxa of small-bodied newts in the genus Lissotriton. The data were analyzed by segmented linear regression to explore patterns of vertebral regionalization and by a two-block partial least squares method to test for morphological integration. All taxa show a morphological shift posterior to the fifth trunk vertebra, which corresponds to the two-region concept. However, morphological integration is found to be strongest in the mid-trunk. Taken jointly, these results indicate a highly integrated presacral vertebral column with a subtle two-region differentiation. The results are discussed in relation to specific functional requirements, developmental and phylogenetic constraints, and specific requirements posed by a biphasic life cycle and different locomotor modes (swimming vs. walking). Further research should be conducted on different ontogenetic stages and closely related but ecologically differentiated species.
... Arguments against a singular explanation for allometries have been made since the conception of the MTE (Glazier 2005(Glazier , 2014(Glazier , 2015(Glazier , 2018a(Glazier , 2018bPrice et al. 2012;Halgrímsson et al. 2019) and even before (von Bertalanffy 1957). Our findings also pose conceptual problems for the MTE and other proposed singleexponent hypotheses for metabolic allometries. ...
Many attempts at providing a single-scale exponent and mechanism to explain metabolic rate assert a monolithic selective mechanism for allometries, characterized by a universal allometric scale power (usually chosen to be 0.75). To test for the deviations from universal allometric scaling, we gathered data from previously published metabolic measurements on 903 bird species and performed regressions of log(basal metabolic rate) and log(body mass) for (1) all birds and (2) 20 monophyletic clades within birds. We constructed two Bayesian linear mixed models-one included ecological variables and the other included data for mammals from Sieg et al. (2009). Overall allometric patterns differed significantly among clades of birds, and some clades were not consistent with the 0.75 scale power. We were unable to find apparent physiological, morphological, phylogenetic, or ecological characteristics among clades, predicting a difference in allometry or consistency with any previously proposed universal allometry. The Bayesian analysis illuminated novel bivariate, clade-specific differences in scaling slope-intercept space, separating large groups of birds and mammals. While significantly related to basal metabolic rate, feeding guild and migratory tendency had small effects compared to clade and body mass. We propose that allometric hypotheses, in general, must extend beyond simple overarching mechanisms to allow for conflicting and interacting influences that produce allometric patterns at narrower taxonomic scales-perhaps including other processes whose optimization may interfere with that of the system proposed by the metabolic theory of ecology.
... Devils have shown their capacity to respond to this disease-induced increased adult mortality with a 16fold increase in the proportion of individuals exhibiting precocious sexual maturity 7.7 A dimensionless invariant: age at maturity/adult lifespan The term "allometry" describes the relationship between various morphological and physiological traits and body size. Allometry can be viewed as a special case of integration or the tendency for traits to covary (Cheverud 1996;Klingenberg 2008;Armbruster et al. 2014;Hallgrímsson et al. 2019), and similar to developmental integration, morphological allometry has been considered both a possible constraint on adaptive evolution (Huxley 1932;Gould 1966;Pélabon et al. 2014;Voje et al. 2014), and itself an adaptation to functional needs (Schmidt-Nielsen 1984;Boduriansky & Day 2003;Frankino et al. 2009;Armbruster et al. 2014). Allometric relationships result from the regulation of scale and proportion by strong natural selection in living organisms (West et al. 1997(West et al. , 1999Bonner & Horn 2000;Frankino et al. 2005; and have a genetic basis (Wu et al. 2002Long et al. 2006;Wu & Hou 2006;Li et al. 2007;Vasseur et al. 2012). ...
... Allometric scaling laws can be described mathematically by a power function B = aM b , where B is a biological variable, a is a constant representing the proportionality coefficient, M is the body weight, a standard measure of body size, and b is the scaling exponent (Calder 1984;Schmidt-Nielsen 1984). Allometry can be viewed as a special case of integration or the tendency for traits to covary (Cheverud 1996;Klingenberg 2008;Hallgrímsson et al. 2019). Allometric relationships result from the regulation of scale and proportion by strong natural selection (Sinervo et al. 1992;West et al. 1997West et al. , 1999Bonner & Horn 2000;Frankino et al. 2005;West & Brown 2005;Houle et al. 2019) in living organisms and are thought to have a genetic component (Wu et al. 2002(Wu et al. , 2003Wu & Hou 2006;Li et al. 2007;Vasseur et al. 2012). ...
... Indeed, in chicken and mice, bone formation depends on functional muscles that perform embryonic muscle contraction [61,62]. Third, the extreme snout elongation of some myrmecophagous placentals, particularly giant and collared anteaters, might have required changes in integration of traits in the rostrum related to myrmecophagy [5,63,64], as somatic growth of bone tissues is one of the main processes contributing to structural covariation on the mammalian skull [3,4,65,66]. To test these predictions, we used geometric morphometrics and both exploratory and confirmatory methods to investigate the previously unexplored modular architecture of the skull in 13 myrmecophagous placental species ( Fig. 1 and Additional file 2: Fig. S1; Additional file 3: Table S1 and S2). ...
Background
The skull of placental mammals constitutes one of the best studied systems for phenotypic modularity. Several studies have found strong evidence for the conserved presence of two- and six-module architectures, while the strength of trait correlations (integration) has been associated with major developmental processes such as somatic growth, muscle-bone interactions, and tooth eruption. Among placentals, ant- and termite-eating (myrmecophagy) represents an exemplar case of dietary convergence, accompanied by the selection of several cranial morphofunctional traits such as rostrum elongation, tooth loss, and mastication loss. Despite such drastic functional modifications, the covariance patterns of the skull of convergently evolved myrmecophagous placentals are yet to be studied in order to assess the potential consequences of this dietary shift on cranial modularity.
Results
Here, we performed a landmark-based morphometric analysis of cranial covariance patterns in 13 species of myrmecophagous placentals. Our analyses reveal that most myrmecophagous species present skulls divided into six to seven modules (depending on the confirmatory method used), with architectures similar to those of non-myrmecophagous placentals (therian six modules). Within-module integration is also similar to what was previously described for other placentals, suggesting that most covariance-generating processes are conserved across the clade. Nevertheless, we show that extreme rostrum elongation and tooth loss in myrmecophagid anteaters have resulted in a shift in intermodule correlations in the proximal region of the rostrum. Namely, the naso-frontal and maxillo-palatine regions are strongly correlated with the oro-nasal module, suggesting an integrated rostrum conserved from pre-natal developmental processes. In contrast, the similarly toothless pangolins show a weaker correlation between the anterior rostral modules, resembling the pattern of toothed placentals.
Conclusions
These results reveal that despite some integration shifts related to extreme functional and morphological features of myrmecophagous skulls, cranial modular architectures have conserved the typical mammalian scheme.
... Jerison's extensive study of static brain/body size allometry of adult vertebrates established a method for studying mammalian brains; it did not, however, include their ontogenetic development [9]. Since, however, static allometry is a result of variations in developmental (ontogenetic) processes [10], study of ontogenetic brain size/body size allometry is important. This has been recently summarised by Montgomery et al. [11], and further discussed by Packard (2019) and Tsuboi (2019) [12,13]. ...
There exists a negative allometry between vertebrate brain size and body size. It has been
well studied among placental mammals but less is known regarding marsupials. Consequently, this study explores brain/body ontogenetic growth in marsupials and compares it with placental mammals. Pouch young samples of 43 koalas (Phascolarctos cinereus), 28 possums (Trichosurus vulpecula), and 36 tammar wallabies (Macropus eugenii) preserved in a solution of 10% buffered formalin, as well as fresh juveniles and adults of 43 koalas and 40 possums, were studied. Their brain size/body size allometry was compared to that among humans, rhesus monkeys, dogs, cats, rats, guinea pigs, rabbits, wild pigs, and mice. Two patterns of allometric curves were found: a logarithmic one (marsupials, rabbits, wild pigs, and guinea pigs) and a logistic one (the rest of mammals)
... Shared developmental pathways lead to correlated morphological variation, or morphological integration [51][52][53][54][55][56][57] . To enable analyses of integration, we added landmark configurations and segmentations to different regions of the adult skull atlas. ...
Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses. To enable meta-analyses of morphological variation, particularly in the craniofacial complex and brain, we created MusMorph, a database of standardized mouse morphology data spanning numerous genotypes and developmental stages, including E10.5, E11.5, E14.5, E15.5, E18.5, and adulthood. To standardize data collection, we implemented an atlas-based phenotyping pipeline that combines techniques from image registration, deep learning, and morphometrics. Alongside stage-specific atlases, we provide aligned micro-computed tomography images, dense anatomical landmarks, and segmentations (if available) for each specimen ( N = 10,056). Our workflow is open-source to encourage transparency and reproducible data collection. The MusMorph data and scripts are available on FaceBase ( www.facebase.org , 10.25550/3-HXMC ) and GitHub ( https://github.com/jaydevine/MusMorph ).
... Since allometry generates shape variation that is totally concentrated in one dimension of the shape space, it is certainly a factor that could contribute to integration trough a complete morphological structure. Consequently, it is highly relevant to consider allometry when carrying out analyses concerning morphological integration and morphological variation [8,22,24,26,52,55,[63][64][65][66][67][68]. We assessed the covariance matrices of the residual values of the multivariate regression of shape on centroid size at the different levels, discovering that irrespective of size correction, the values of integration throughout the entire structure and between parts were not influenced. ...
Static, developmental, and evolutionary variation are different sources of morphological variation which can be quantified using morphometrics tools. In the present study we have carried out a comparative multiple level study of integration (i.e., static, developmental, and evolutionary) to acquire insight about the relationships that exist between different integration levels, as well as to better understand their involvement in the evolutionary processes related to the diversification of Drosophila’s wing shape. This approach was applied to analyse wing evolution in 59 species across the whole genus in a large dataset (~10,000 wings were studied). Static integration was analysed using principal component analysis, thus providing an integration measurement for overall wing shape. Developmental integration was studied between wing parts by using a partial least squares method between the anterior and posterior compartments of the wing. Evolutionary integration was analysed using independent contrasts. The present results show that all Drosophila species exhibit strong morphological integration at different levels. The strong integration and overall similarities observed at multiple integration levels suggest a shared mechanism underlying this variation, which could result as consequence of genetic drift acting on the wing shape of Drosophila.
... We managed to collect BM estimation for only 34 of the 53 taxa constituting our sample. Consequently, we also consider the centroid size (CS) of each bone, which is classically used to address allometric variation, i.e. the shape variation linked to size (Zelditch et al., 2012;Mitteroecker et al., 2013;Klingenberg, 2016;Hallgrímsson et al., 2019). CS is defined as the square root of the sum of the square of the distance of each point to the centroid of the landmark set (Zelditch et al., 2012). ...
Weight support is a strong functional constraint modelling limb bones in heavy quadrupeds. However, the complex relations between bone shape, mass, size and body proportions have been poorly explored. Rhinocerotoidea is one of the groups showing the highest body mass reached by terrestrial mammals through time. Here, we explore the evolutionary variation of shape in hindlimb stylopod and zeugopod bones and its relationship with mass, size and gracility in this superfamily. Our results show that bones undergo a general increase in robustness towards high masses, associated with reinforcements of the main muscle insertions. The shape of the femur, carrying a marked phylogenetic signal, varies conjointly with mass, size and gracility, whereas that of the tibia appears related to gracility and mass only. The shape of the fibula does not vary according to that of the tibia. Moreover, congruent variation of shape between the distal part of the femur and the complete tibia underlines the potentially strong covariation of the elements constituting the knee joint. These results, coupled with those previously obtained from forelimb study, allow a better comprehension of the relationship between bone shape and mass among Rhinocerotoidea, and a refining of the concept of 'graviportality' in this superfamily.
... We managed to collect BM estimation for only 40 of the 69 taxa constituting our sample. Consequently, we chose to also consider the centroid size (CS) of each bone, which is classically used to address allometric variation, i.e. shape variation linked to size (Zelditch et al., 2012;Mitteroecker et al., 2013;Klingenberg, 2016;Hallgrímsson et al., 2019). Centroid size, defined as the square root of the sum of the square of the distance of each point to the centroid of the landmark set (Zelditch et al., 2012), is known to be a good proxy of the mass of the animal (Ercoli & Prevosti, 2011;Cassini et al., 2012), especially for limb bones of rhinoceros (Mallet et al., 2019;Etienne et al., 2020). ...
In quadrupeds, limb bones are strongly affected by functional constraints linked to weight support, but few studies have addressed the complementary effects of mass, size and body proportions on limb bone shape. During their history, Rhinocerotoidea have displayed a great diversity of body masses and relative size and proportions of limb bones, from small tapir-like forms to giant species. Here, we explore the evolutionary variation of shapes in forelimb bones and its relationship with body mass in Rhinocerotoidea. Our results indicate a general increase in robustness and greater development of muscular insertions in heavier species, counteracting the higher weight loadings induced by an increased body mass. The shape of the humerus changes allometrically and exhibits a strong phylogenetic signal. Shapes of the radius and ulna display a stronger link with body mass repartition than with the absolute mass itself. Congruent shape variation between the humerus and the proximal part of the ulna suggests that the elbow joint is comprised of two strongly covariant structures. In addition, our work confirms the uniqueness of giant Paraceratheriidae among Rhinocerotoidea, whose shape variation is related to both a high body mass and a cursorial forelimb construction.
... In both substructures, allometry represents a small but significant component of shape variation: UBB and MAN shape are significantly positively associated with their respective centroid size (UBB R 2 = 0.109, p < 0.001; MAN R 2 = 0.069, p < 0.001); birds with larger head skeletons have a straighter, longer UBB and wider MAN (Supplemental Figure 8A-C). Allometry is an evolutionarily important associate of shape (De Beer 1940;Alberch et al. 1979;Hallgrímsson et al. 2019); however, we focused our further analyses on non-allometric shape variation within the Pom x Scan F 2 population by using the residuals from the shape ~ centroid size regression. ...
Deciphering the genetic basis of vertebrate craniofacial variation is a longstanding biological problem with broad implications in evolution, development, and human pathology. One of the most stunning examples of craniofacial diversification is the adaptive radiation of birds, in which the beak serves essential roles in virtually every aspect of their life histories. The domestic pigeon (Columba livia) provides an exceptional opportunity to study the genetic underpinnings of craniofacial variation because of its unique balance of experimental accessibility and extraordinary phenotypic diversity within a single species. We used traditional and geometric morphometrics to quantify craniofacial variation in an F2 laboratory cross derived from the straight-beaked Pomeranian Pouter and curved-beak Scandaroon pigeon breeds. Using a combination of genome-wide quantitative trait locus scans and multi-locus modeling, we identified a set of genetic loci associated with complex shape variation in the craniofacial skeleton, including beak shape, braincase shape, and mandible shape. Some of these loci control coordinated changes between different structures, while others explain variation in the size and shape of specific skull and jaw regions. We find that in domestic pigeons, a complex blend of both independent and coupled genetic effects underlie three-dimensional craniofacial morphology.
... Tree dimensions and their proportions (i.e., allometry) are influenced by the surrounding environment [58,59], as well as by a tree's fitness [60] and genetic potential [61]. The differences in tree dimensions among QURO varieties observed in this study are in line with the high variation in the biomass production of QURO across the different provenances [46]. ...
This paper presents an analysis of the radial growth, tree dimensions, and allometry of three phenological pedunculate oak (Quercus robur L.; QURO) varieties (early (E-QURO), typical (T-QURO), and late (L-QURO)), from a common garden experiment. We focused on the resistance and resilience of each variety to drought events, which occurred in 2012 and 2017, as well as their recovery potential during juvenile and mature growth phases, with the goal of clarifying how QURO drought sensitivity is influenced by tree phenology and growth stage. Our results indicate that E-QURO is more drought resistant, while T-QURO and L-QURO exhibit greater recovery potential after a drought event. Hence, typical and late QURO varieties are better prepared to withstand climate change. We also noted differences in the physical dimensions and the allometry of the studied QURO varieties. On average, 21-year-old QURO specimens from the analyzed stand are 9.35 m tall, have a crown width (CW) of 8.05 m, and a diameter at breast height (DBH) of 23.71 cm. Although T-QURO varieties had the greatest DBH and CW, they were shorter than E- and L-QURO, which are similar in height. T-QURO is also shorter relative to DBH, while L-QURO has a wider crown relative to tree height (TH). Intra-variety variations are higher than variations among half-sib (open-pollinated) families of each variety. Moreover, the adopted regression model provided a better fit to the CW/DBH ratio than to TH/DBH and CW/TH.
... Required relationships were those dictated by genetic, mechanical or developmental forces within an individual, whereas functional relationships are caused by natural selection favouring particular trait combinations. More recently, 'required' relationships have been cast in terms of genetic cascades and pleiotropy [10][11][12]. A single gene promoting growth in both fore-and hindlimb modules is an example of a required constraint. ...
Adaptive radiations fill ecological and morphological space during evolutionary diversification. Why do some trait combinations evolve during such radiations, whereas others do not? ‘Required’ constraints of pleiotropy and developmental interaction frequently are implicated in explanations for such patterns, but selective forces also may discourage particular trait combinations. Here, we use a dataset of 351 species to demonstrate the dearth of some theoretically plausible trait combinations of limb, toe and tail length in Anolis lizards. For example, disproportionately few Anolis species display long limbs and short toes. We evaluate recovered patterns within three species of Anolis , and find that cladewide patterns are not evident at intraspecific levels. For example, within species, the combination of long limbs and short toes is not significantly rarer than long limbs and long toes. Differences in scale complicate inter- and intraspecific comparisons and disallow concrete conclusions of cause. However, the absence of the interspecific pattern at the intraspecific level is more compatible with selection favouring particular trait combinations than with ‘required’ forces dictating which trait combinations are available for selection. We also demonstrate the isometry of toe, tail and hindlimb length relative to body length between species but allometry in four of nine trait–body comparisons within species.
... For instance, if a trait is disproportionately large in larger species relative to smaller species or disproportionately large in small species relative to large species, then this might suggest that historical selection favouring larger trait size has been stronger within larger or smaller species, respectively (Frankino et al., 2005). Because body size is often a target of selection directly (Siepielski et al., 2019) and may be strongly correlated with trait size, phenotypic response to selection acting on the size of a trait may be constrained or facilitated by the correlation that that trait shares with body size (Hallgrímsson et al., 2019). Thus, understanding the evolution of primary sexual traits is not complete without understanding how its relationship to body size changes across species' divergence. ...
Because ‘primary’ sexual characteristics (i.e. those directly associated with reproduction) can be extremely variable, evolve quickly, and can be impacted by both natural and sexual selection, they are often considered excellent model systems in which to study evolution. Here, we explore the evolution of the anal sheath, a trait hypothesized to facilitate the release and proper placement of eggs on the spawning substrate, and its relationship to spawning habitat and maximum body size in a family of fish (Fundulidae). In addition to using phylogenetically informed statistics to determine the role of preferred spawning habitat and maximum body size on the evolution of anal sheath length, we reconstruct the evolutionary history of the anal sheath and preferred spawning habitat. We then test for significant phylogenetic signal and evolutionary rate shifts in the size of the anal sheath and the preferred spawning habitat. Our results indicate that preferred spawning habitat, and not maximum body length, significantly influences anal sheath size, which is associated with a significant phylogenetic signal, and an evolutionary rate similar to that of preferred spawning substrate. We discuss these results in terms of potential evolutionary mechanisms driving anal sheath length.
... These two phenomenological interpretations of allometry (referring to the Huxley-Jolicoeur and Gould-Mosimann schools, respectively) differ significantly in terms of the methods used for approaching the issue. Nevertheless, both approaches agree on defining allometry as the tendency of different biological attributes to co-vary under the influence of developmental processes regulating body size [24]. More explicitly, allometry explores the consequences of the variation in size of whole organisms on the variation in size, shape and/or function of single traits. ...
Joint hypermobility is a common characteristic in humans. Its non-casual association with various musculoskeletal complaints is known and currently defined as "the spectrum". It includes hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). hEDS is recognized by a set of descriptive criteria, while HSD is the background diagnosis for individuals not fulfilling these criteria. Little is known about the etiopathogenesis of "the spectrum". It may be intended as a complex trait according to the integration model. Particularly, "the spectrum" is common in the general population, affects morphology, presents extreme clinical variability, and is characterized by marked sex bias without a clear Mendelian or hormonal explanation. Joint hypermobility and the other hEDS "systemic" criteria are intended as qualitative derivatives of continuous traits of normal morphological variability. The need for a minimum set of criteria for hEDS diagnosis implies a tendency to co-vary these underlying continuous traits. In evolutionary biology, such a covariation (i.e. integration) is driven by multiple forces, including genetic, developmental, functional and environmental/acquired interactors. The etiopathogenesis of "the spectrum" may be resolved by a deeper understanding of phenotypic variability, which, superimposes with normal morphological variability.
... I managed to collect BM estimation for only 40 over the 69 taxa constituting my sample. Consequently, I chose to also consider the centroid size (CS) of each bone, which is classically used to address allometric variation, i.e. the shape variation linked to size (Zelditch et al., 2012;Mitteroecker et al., 2013;Klingenberg, 2016;Hallgrímsson et al., 2019). Centroid size, defined as the square root of the sum of the square of the distance of each point to the centroid of the landmark set (Zelditch et al., 2012), is known to be a good proxy of the mass of the animal (Ercoli & Prevosti, 2011;Cassini, Vizcaíno & Bargo, 2012), especially for limb bones of rhinoceros (Mallet et al., 2019;Etienne et al., 2020). ...
In terrestrial vertebrates, the shape of the limb bones is influenced, among other factors, by functional constraints, notably the need to resist loading stresses due to gravity. This led, in quadrupeds weighting hundreds of kilograms, to morphological modifications of the limb bones to avoid crushing. Such architectural modifications related to a heavy weight have been historically qualified as “graviportal”. Rhinocerotoidea are of particular interest to study the morphological changes of the limb bones related to body mass, as they are represented by five extant species and dozens of fossil genera, some being among the heaviest land mammals that ever existed. Several independent occurrences of an increase of body mass are observed in this superfamily, making it relevant to study the variation of shape in relation to weight. This work explores the shape variation of the limb long bones relatively to body mass and body proportions among Rhinocerotoidea along their evolutionary history, in order to better understand how the skeleton modifies to meet the functional requirements of a coordinated locomotion and the support of a heavy weight. To do so, I used a 3D geometric morphometrics approach to qualify and quantify the shape of the six bones composing the stylopodium and zeugopodium of a sample of modern and fossil specimens. The exploration of the long bone shape variation and covariation in relation to body mass and to the evolutionary legacy in modern rhinos has been completed by the study of numerous fossil representatives to cover a large range of weight and body proportions, taking into account the evolutionary history of the group. My work highlights an increase of bone robustness common to all heavy rhinos. The development of the insertions for powerful extensor muscles and the likely presence of passive-stay apparatuses at shoulder and knee joints in heavy rhino taxa allow to better resist flexion caused by loading forces. My results show that forelimb bones are more influenced by body mass variation than hind limb ones in Rhinocerotoidea, likely due to the different proportion of body mass that they support and to their distinct respective roles of brake and propulsion. The shape of the stylopodium bones is simultaneously related to evolutionary legacy and body mass, while that of the zeugopodium is mostly associated with the degree of brachypody (i.e., relative limb length). The fibula is the only bone showing puzzling patterns of shape variation dominated by intraspecific variations, which questions its functional role in weight bearing. The shape variation in Rhinocerotoidea carries a dual signal with uniform aspects shared by all heavy species coupled with specific features in the different taxa, corresponding to the multiplicity of limb constructions observed in the superfamily. In addition to modifications related to heavy weight, most Rhinocerotoidea retain features of running quadrupeds while displaying different ways to sustain a high mass, questioning the classical definition of graviportality mainly based on elephants. This highlights the necessity to redefine graviportality by highlighting what are the repeated features potentially linked to it in each group with independent occurrences of heavy weight.
... Theoretically, RRM has been used to model genetic changes of growth and developmental traits with age in plant and animals, and was able to analyze both static and ontogenetic allometry scalings. When growth and developmental traits were repeatedly measured, the RRM for ontogenetic allometry scalings could better characterize genetic changes in allometries by additionally taking into account time dependent permanent environment effects [42]. In this study, application of RRM to genetic analysis for static allometry scalings was conducted because the traits were measured only once in slaughter period. ...
In animal breeding, body components and metabolic traits always fall behind body weights in genetic improvement, which leads to the decline in standards and qualities of animal products. Phenotypically, the relative growth of multiple body components and metabolic traits relative to body weights are characterized by using joint allometric scaling models, and then random regression models (RRMs) are constructed to map quantitative trait loci (QTLs) for relative grwoth allometries of body compositions and metabolic traits in chicken. Referred to as real joint allometric scaling models, statistical utility of the so-called LASSO-RRM mapping method is given a demonstration by computer simulation analysis. Using the F2 population by crossing broiler × Fayoumi, we formulated optimal joint allometric scaling models of fat, shank weight (shank-w) and liver as well as thyroxine (T4) and glucose (GLC) to body weights. For body compositions, a total of 9 QTLs, including 4 additive and 5 dominant QTLs, were detected to control the allometric scalings of fat, shank-w, and liver to body weights; while a total of 10 QTLs of which 6 were dominant, were mapped to govern the allometries of T4 and GLC to body weights. We characterized relative growths of body compositions and metabolic traits to body weights in broilers with joint allometric scaling models and detected QTLs for the allometry scalings of the relative growths by using RRMs. The identified QTLs, including their highly linked genetic markers, could be used to order relative growths of the body components or metabolic traits to body weights in marker-assisted breeding programs for improving the standard and quality of broiler meat products.
... If these constituted the state of the CLCA, then each would have required re-establishment to the primitive state in the hominin lineage in Prang's (2019) scenario. Such reversals are, of course, not impossible as the genetic foundation of linear traits is complex (Hallgrímsson et al., 2019), with some 'atavistic' soft-tissue traits appearing often as anomalies in humans (Chaney et al., 2018;Boyle et al., 2020). However, simply ignoring these traits unnecessarily limits the use of available evidence. ...
... Metabolic allometry during development is receiving considerable attention, and its underlying mechanisms being debated (Hallgrímsson et al., 2019;Vollmer et al., 2017). Ironically, a basic tenet of development is that physiological state constantly changes, yet a basic tenet of allometry is that animals must be compared only in the same physiological state, potentially nullifying traditional analytical approaches used in interspecific allometry. ...
The August Krogh principle has guided many comparative physiological studies, being especially useful for developmental physiology. Several attributes of unusual, if not unique, animals enable researchers to understand developmental phenomena more generally – the essence of the Krogh principle. This article provides examples of unusual traits of animals currently being used to understand development and reproduction. 1) Accelerated development greatly minimizes time spent examining how animals develop across time from egg to adult. For example, the tropical gar begins to breath air within as little as 2.5 days after hatching – much faster than other air-breathing fishes - facilitating study of the development of respiratory reflexes in fishes. 2) Transparency of the body wall has been exploited to image cardiac output in near-microscopic larvae of the zebrafish and mahi mahi, and to capitalize on bacterial biosensors to investigate development of in vivo digestive function in Caenorhabditis elegans. 3) Gigantism, as in the chicken-sized embryos of the emu, or the larvae of the paradoxical frog, allows surgeries not otherwise feasible. 4) Reproductive traits such as polyembryony in armadillos and parthenogenesis in planaria have informed us about classic gene vs. environment questions. Finally, 5) large body mass range enables clearer allometric analyses. Insects like the silk moth, show a more than a 1000-fold difference between eggs and adults. The August Krogh principle, then, is not simply to justify the study of exotic animals (as interesting as that is!), but has been used to generate a broader synthesis and understanding of all taxa.
... At a mechanistic level, such a coordination of individual development can arise from mechanical interactions and chemical signaling across developing tissues or from growth factors with systemic effects. At the population level, integrated variation of otherwise independent elements can result from the evolutionary fine-tuning of pleiotropic gene effects (Cheverud 1982(Cheverud , 1984Zelditch et al. 2006;Hallgrimsson et al. 2007b;Mitteroecker et al. 2012;Pavlicev and Wagner 2012;Armbruster et al. 2014;Hall 2015;Hallgrímsson et al. 2019). Some of these genetic and developmental factors may have similarly directed effects on related structures, causing coordinated variation. ...
It is a classic aim of quantitative and evolutionary biology to infer genetic architecture and potential evolutionary responses to selection from the variance-covariance structure of measured traits. But a meaningful genetic or developmental interpretation of raw covariances is difficult, and classic concepts of morphological integration do not directly apply to modern morphometric data. Here we present a new morphometric strategy based on the comparison of morphological variation across different spatial scales. If anatomical elements vary completely independently, then their variance accumulates at larger scales or for structures composed of multiple elements: morphological variance would be a power function of spatial scale. Deviations from this pattern of "variational self-similarity" (serving as a null-model of completely uncoordinated growth) indicate genetic or developmental co-regulation of anatomical components. We present biometric strategies and R scripts for identifying patterns of coordination and compensation in the size and shape of composite anatomical structures. In an application to human cranial variation, we found that coordinated variation and positive correlations are prevalent for the size of cranial components, whereas their shape was dominated by compensatory variation, leading to strong canalization of cranial shape at larger scales. We propose that mechanically induced bone formation and remodeling are key mechanisms underlying compensatory variation in cranial shape. Such epigenetic coordination and compensation of growth are indispensable for stable, canalized development and may also foster the evolvability of complex anatomical structures by preserving spatial und functional integrity during genetic responses to selection.
The mammalian cranium (skull without lower jaw) is representative of mammalian diversity and is thus of particular interest to mammalian biologists across disciplines. One widely retrieved pattern accompanying mammalian cranial diversification is referred to as ‘craniofacial evolutionary allometry’ (CREA). This posits that adults of larger species, in a group of closely related mammals, tend to have relatively longer faces and smaller braincases. However, no process has been officially suggested to explain this pattern, there are many apparent exceptions, and its predictions potentially conflict with well‐established biomechanical principles. Understanding the mechanisms behind CREA and causes for deviations from the pattern therefore has tremendous potential to explain allometry and diversification of the mammalian cranium. Here, we propose an amended framework to characterise the CREA pattern more clearly, in that ‘longer faces’ can arise through several kinds of evolutionary change, including elongation of the rostrum, retraction of the jaw muscles, or a more narrow or shallow skull, which all result in a generalised gracilisation of the facial skeleton with increased size. We define a standardised workflow to test for the presence of the pattern, using allometric shape predictions derived from geometric morphometrics analysis, and apply this to 22 mammalian families including marsupials, rabbits, rodents, bats, carnivores, antelopes, and whales. Our results show that increasing facial gracility with size is common, but not necessarily as ubiquitous as previously suggested. To address the mechanistic basis for this variation, we then review cranial adaptations for harder biting. These dictate that a more gracile cranium in larger species must represent a structural sacrifice in the ability to produce or withstand harder bites, relative to size. This leads us to propose that facial gracilisation in larger species is often a product of bite force allometry and phylogenetic niche conservatism, where more closely related species tend to exhibit more similar feeding ecology and biting behaviours and, therefore, absolute (size‐independent) bite force requirements. Since larger species can produce the same absolute bite forces as smaller species with less effort, we propose that relaxed bite force demands can permit facial gracility in response to bone optimisation and alternative selection pressures. Thus, mammalian facial scaling represents an adaptive by‐product of the shifting importance of selective pressures occurring with increased size. A reverse pattern of facial ‘shortening’ can accordingly also be found, and is retrieved in several cases here, where larger species incorporate novel feeding behaviours involving greater bite forces. We discuss multiple exceptions to a bite force‐mediated influence on facial proportions across mammals which lead us to argue that ecomorphological specialisation of the cranium is likely to be the primary driver of facial scaling patterns, with some developmental constraints as possible secondary factors. A potential for larger species to have a wider range of cranial functions when less constrained by bite force demands might also explain why selection for larger sizes seems to be prevalent in some mammalian clades. The interplay between adaptation and constraint across size ranges thus presents an interesting consideration for a mechanistically grounded investigation of mammalian cranial allometry.
The diversity of functional anatomy related to feeding is particularly impressive in fishes and correlates with various ecological specializations across species. Polymorphism within species can manifest in divergent feeding morphology and ecology, often along a benthic pelagic axis. Arctic charr (Salvelinus alpinus) is a freshwater salmonid known for morphological variation and sympatric polymorphism. In Lake Þingvallavatn, Iceland, four morphs of arctic charr coexist that differ in preferred prey, behaviour, habitat use, and external feeding morphology. We studied variation in upper and lower jaw bones (six bones total) related to feeding, in adults of the four morphs using geometric morphometrics and univariate statistics. We tested for allometric differences in bone size and shape among morphs, morph effects on bone size and shape, and if benthic and pelagic ecologies associate with bone size and shape. We also examined the degree of integration between bone pairs. We found differences in bone size between pelagic and benthic morphs for two bones (dentary and premaxilla). There was clear bone shape divergence along a benthic pelagic axis in four bones (dentary, articular-angular, premaxilla and maxilla), as well as allometric differences between morphs in the dentary. Most dramatic was the dentary, where morph explained more shape variation than bone size. Comparatively, benthic morphs possess a compact and taller dentary, with shorter dentary palate, consistent with visible (but less prominent) differences in external morphology. As these morphs emerged in the last 10,000 years, these results indicate rapid functional evolution of specific feeding structures in arctic charr. This sets the stage for studies of the genetics and development of rapid and parallel craniofacial evolution.
Podocopa ostracods have abounded in various marine and non‐marine habitats since the early Palaeozoic and left a diverse fossil record in strata worldwide. This is particularly useful for stratigraphic correlation and palaeoenvironmental and palaeogeographical reconstructions. However, despite being the most numerous ostracods during the Palaeozoic, their origins, evolution, ontogeny and phylogeny remain poorly defined. This paper represents the first study of morphological variation in Devonian Platycopida ostracods (an order of Podocopa) using a geometric morphometric approach. Our results identify substantial shape variation in Cribroconcha honggulelengensis Song & Crasquin from the Upper Devonian Hongguleleng Formation of western Junggar, northwest China, demonstrating a remarkable change in juveniles between stages A‐3 and A‐2. Using linear regressions between principal component scores from right lateral view and carapace length, we demonstrate allometric growth patterns for this species. The body plan of C. honggulelengensis developed along an ontological variable: from an ovate outline with rare pores to an oblong outline with dense and large pores. Environmental factors should play an important role in shape determination during ontogeny of C. honggulelengensis.
Evolvability is best addressed from a multi-level, macroevolutionary perspective through a comparative approach that tests for among-clade differences in phenotypic diversification in response to an opportunity, such as encountered after a mass extinction, entering a new adaptive zone, or entering a new geographic area. Analyzing the dynamics of clades under similar environmental conditions can (partially) factor out shared external drivers to recognize intrinsic differences in evolvability, aiming for a macroevolutionary analog of a common-garden experiment. Analyses will be most powerful when integrating neontological and paleontological data: determining differences among extant populations that can be hypothesized to generate large-scale, long-term contrasts in evolvability among clades; or observing large-scale differences among clade histories that can by hypothesized to reflect contrasts in genetics and development observed directly in extant populations. However, many comparative analyses can be informative on their own, as explored in this overview. Differences in clade-level evolvability can be visualized in diversity-disparity plots, which can quantify positive and negative departures of phenotypic productivity from stochastic expectations scaled to taxonomic diversification. Factors that evidently can promote evolvability include modularity—when selection aligns with modular structure or with morphological integration patterns; pronounced ontogenetic changes in morphology, as in allometry or multiphase life cycles; genome size; and a variety of evolutionary novelties, which can also be evaluated using macroevolutionary lags between the acquisition of a trait and phenotypic diversification, and dead-clade-walking patterns that may signal a loss of evolvability when extrinsic factors can be excluded. High speciation rates may indirectly foster phenotypic evolvability, and vice versa. Mechanisms are controversial, but clade evolvability may be higher in the Cambrian, and possibly early in the history of clades at other times; in the tropics; and, for marine organisms, in shallow-water disturbed habitats.
Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses. To enable meta-analyses of morphological variation, particularly in the craniofacial complex and brain, we created MusMorph, a database of standardized mouse morphology data spanning numerous genotypes and developmental stages, including E10.5, E11.5, E14.5, E15.5, E18.5, and adulthood. To standardize data collection, we implemented an atlas-based phenotyping pipeline that combines techniques from image registration, deep learning, and morphometrics. Alongside stage-specific atlases, we provide aligned micro-computed tomography images, dense anatomical landmarks, and segmentations (if available) for each specimen (N=10,056). Our workflow is open-source to encourage transparency and reproducible data collection. The MusMorph data and scripts are available on FaceBase (www.facebase.org, doi.org/10.25550/3-HXMC) and GitHub (https://github.com/jaydevine/MusMorph).
Vertebrate craniofacial morphogenesis is a highly orchestrated process that is directed by evolutionarily conserved developmental pathways.1,2 Within species, canalized development typically produces modest morphological variation. However, as a result of millennia of artificial selection, the domestic pigeon displays radical craniofacial variation within a single species. One of the most striking cases of pigeon craniofacial variation is the short-beak phenotype, which has been selected in numerous breeds. Classical genetic experiments suggest that pigeon beak length is regulated by a small number of genetic factors, one of which is sex linked (Ku2 locus).3-5 However, the genetic underpinnings of pigeon craniofacial variation remain unknown. Using geometric morphometrics and quantitative trait locus (QTL) mapping on an F2 intercross between a short-beaked Old German Owl (OGO) and a medium-beaked Racing Homer (RH), we identified a single Z chromosome locus that explains a majority of the variation in beak morphology in the F2 population. Complementary comparative genomic analyses revealed that the same locus is strongly differentiated between breeds with short and medium beaks. Within the Ku2 locus, we identified an amino acid substitution in the non-canonical Wnt receptor ROR2 as a putative regulator of pigeon beak length. The non-canonical Wnt pathway serves critical roles in vertebrate neural crest cell migration and craniofacial morphogenesis.6,7 In humans, ROR2 mutations cause Robinow syndrome, a congenital disorder characterized by skeletal abnormalities, including a widened and shortened facial skeleton.8,9 Our results illustrate how the extraordinary craniofacial variation among pigeons can reveal genetic regulators of vertebrate craniofacial diversity.
Intra‐specific variation pattern is informative to understanding the evolution of morphological traits, but has been rarely studied in jumping spiders. Here we investigate the intra‐specific variation of non‐genitalic and genitalic traits in two euophryine jumping spider species that show considerable difference in sexual dimorphism: Chapoda recondita (Peckham & Peckham, 1896) and Antillattus cambridgei (Bryant, 1943). The results show the pre‐copulatory sexually selected traits (e.g. male chelicerae) tend to have positive intra‐specific allometry, and thus may have evolved under strong directional selection. The genitalic traits and some non‐genitalic traits tend to show negative allometries. Unlike non‐genitalic traits, the genitalic traits usually have high size‐corrected intra‐specific variation (CV’). Factors that may account for the negative allometry and high size‐corrected intra‐specific variation in genitalic traits are discussed. Pre‐ and post‐copulatory sexual selection may coexist in species and whether there is a trade‐off between these two selection mechanisms remains to be investigated. We found that the genitalic and non‐genitalic traits show different intra‐specific variation patterns in two euophryine jumping spider species, Chapoda recondita and Antillattus cambridgei. The genitalic traits show negative intra‐specific allometry but high size‐corrected intra‐specific variation, whereas the pre‐copulatory sexually‐selected traits (e.g. male chelicerae) that may have evolved under strong directional selection show positive allometry.
Geometric morphometrics is the statistical analysis of landmark-based shape variation and its covariation with other variables. Over the past two decades, the gold standard of landmark data acquisition has been manual detection by a single observer. This approach has proven accurate and reliable in small-scale investigations. However, big data initiatives are increasingly common in biology and morphometrics. This requires fast, automated, and standardized data collection. We combine techniques from image registration, geometric morphometrics, and deep learning to automate and optimize anatomical landmark detection. We test our method on high-resolution, micro-computed tomography images of adult mouse skulls. To ensure generalizability, we use a morphologically diverse sample and implement fundamentally different deformable registration algorithms. Compared to landmarks derived from conventional image registration workflows, our optimized landmark data show up to a 39.1% reduction in average coordinate error and a 36.7% reduction in total distribution error. In addition, our landmark optimization produces estimates of the sample mean shape and variance–covariance structure that are statistically indistinguishable from expert manual estimates. For biological imaging datasets and morphometric research questions, our approach can eliminate the time and subjectivity of manual landmark detection whilst retaining the biological integrity of these expert annotations.
The biology of how faces are built and come to differ from one another is complex. Discovering normal variants that contribute to differences in facial morphology is one key to untangling this complexity, with important implications for medicine and evolutionary biology. This study maps quantitative trait loci (QTL) for skeletal facial shape using Diversity Outbred (DO) mice. The DO is a randomly outcrossed population with high heterozygosity that captures the allelic diversity of eight inbred mouse lines from three subspecies. The study uses a sample of 1147 DO animals (the largest sample yet employed for a shape QTL study in mouse), each characterized by 22 three-dimensional landmarks, 56,885 autosomal and X-chromosome markers, and sex and age classifiers. We identified 37 facial shape QTL across 20 shape principal components (PCs) using a mixed effects regression that accounts for kinship among observations. The QTL include some previously identified intervals as well as new regions that expand the list of potential targets for future experimental study. Three QTL characterized shape associations with size (allometry). Median support interval size was 3.5 Mb. Narrowing additional analysis to QTL for the five largest magnitude shape PCs, we found significant overrepresentation of genes with known roles in growth, skeletal and facial development, and sensory organ development. For most intervals, one or more of these genes lies within 0.25 Mb of the QTL's peak. QTL effect sizes were small, with none explaining more than 0.5% of facial shape variation. Thus, our results are consistent with a model of facial diversity that is influenced by key genes in skeletal and facial development and, simultaneously, is highly polygenic.
The study of phenotypic variation in time and space is central to evolutionary biology. Modern geometric morphometrics is the leading family of methods for the quantitative analysis of biological forms. This set of techniques relies heavily on technological innovation for data acquisition, often in the form of 2D or 3D digital images, and on powerful multivariate statistical tools for their analysis. However, neither the most sophisticated device for computerized imaging nor the best statistical test can produce accurate, robust and reproducible results, if it is not based on really good samples and an appropriate use of the 'measurements' extracted from the data. Using examples mostly from my own work on mammal craniofacial variation and museum specimens, I will show how easy it is to forget these most basic assumptions, while focusing heavily on analytical and visualization methods, and much less on the data that generate potentially powerful analyses and visually appealing diagrams.
The biology of how faces are built and come to differ from one another is complex. Discovering the genes that contribute to differences in facial morphology is one key to untangling this complexity, with important implications for medicine and evolutionary biology. This study maps quantitative trait loci (QTL) for skeletal facial shape using Diversity Outbred (DO) mice. The DO is a randomly outcrossed population with high heterozygosity that captures the allelic diversity of eight inbred mouse lines from three subspecies. The study uses a sample of 1147 DO animals (the largest sample yet employed for a shape QTL study in mouse), each characterized by 22 three-dimensional landmarks, 56,885 autosomal and X-chromosome markers, and sex and age classifiers. We identified 37 facial shape QTL across 20 shape principal components (PCs) using a mixed effects regression that accounts for kinship among observations. The QTL include some previously identified intervals as well as new regions that expand the list of potential targets for future experimental study. Three QTL characterized shape associations with size (allometry). Median support interval size was 3.5 Mb. Narrowing additional analysis to QTL for the five largest magnitude shape PCs, we found significant overrepresentation of genes with known roles in growth, skeletal development, and sensory organ development. For most intervals, one or more of these genes lies within 0.25 Mb of the QTL’s peak. QTL effect sizes were small, with none explaining more than 0.5% of facial shape variation. Thus, our results are consistent with a model of facial diversity that is influenced by key genes in skeletal and facial development and, simultaneously, is highly polygenic.
Author Summary
The mammalian face is a complex structure serving many functions. We studied the genetic basis for facial skeletal diversity in a large sample of mice from an experimental population designed for the study of complex traits. We quantified the contribution of genetic variation to variation in three-dimensional facial shape across more than 55,000 genetic markers spread throughout the mouse genome. We found 37 genetic regions which are very likely to contribute to differences in facial shape. We then conducted a more detailed analysis of the genetic regions associated with the most variable aspects of facial shape. For these regions, a disproportionately large number of genes are known to be important to growth and to skeletal and facial development. The magnitude of these genetic contributions to differences in facial shape are consistently small. Our results therefore support the notion that facial skeletal diversity is influenced by many genes of small effect, but that some of these small effects may be related to genes that are fundamental to skeletal and facial development.
It has been suggested that larger species of mammals tend to become long-faced when they diverge in size during an evolutionary radiation. However, whether this allometric pattern, reminiscent of ontogenetic changes in skull proportions, is indeed a rule has yet to be thoroughly tested. Using ~ 6000 adult specimens from 14 phylogenetically well separated and ecomorphologically distinctive lineages, 11 orders, and all superorders of the placentals, I tested each group for positive craniofacial allometry (CREA). The evidence supporting CREA is overwhelming, with virtually all analyses showing proportionally longer faces in bigger species. This corroborates previous studies in other groups, consolidates CREA as a pervasive morphological trend in placental evolution and opens important research avenues for connecting micro- and macro-evolution. If found in even more lineages of non-placental mammals, confirmed in birds, and possibly discovered in other tetrapods, CREA could become one of the most general rules of morphological evolution in land vertebrates.
R/qtl2 is an interactive software environment for mapping quantitative trait loci (QTL) in experimental populations. The R/qtl2 software expands the scope of the widely-used R/qtl software package to include multiparental populations, better handles modern high-dimensional data....
R/qtl2 is an interactive software environment for mapping quantitative trait loci (QTL) in experimental populations. The R/qtl2 software expands the scope of the widely used R/qtl software package to include multiparent populations derived from more than two founder strains, such as the Collaborative Cross and Diversity Outbred mice, heterogeneous stocks, and MAGIC plant populations. R/qtl2 is designed to handle modern high-density genotyping data and high-dimensional molecular phenotypes, including gene expression and proteomics. R/qtl2 includes the ability to perform genome scans using a linear mixed model to account for population structure, and also includes features to impute SNPs based on founder strain genomes and to carry out association mapping. The R/qtl2 software provides all of the basic features needed for QTL mapping, including graphical displays and summary reports, and it can be extended through the creation of add-on packages. R/qtl2, which is free and open source software written in the R and C++ programming languages, comes with a test framework.
Background:
Previous analysis suggested that the relative contribution of individual bones to regional skull lengths differ between inbred mouse strains. If the negative correlation of adjacent bone lengths is associated with genetic variation in a heterogeneous population, it would be an example of negative pleiotropy, which occurs when a genetic factor leads to opposite effects in two phenotypes. Confirming negative pleiotropy and determining its basis may reveal important information about the maintenance of overall skull integration and developmental constraint on skull morphology.
Results:
We identified negative correlations between the lengths of the frontal and parietal bones in the midline cranial vault as well as the zygomatic bone and zygomatic process of the maxilla, which contribute to the zygomatic arch. Through gene association mapping of a large heterogeneous population of Diversity Outbred (DO) mice, we identified a quantitative trait locus on chromosome 17 driving the antagonistic contribution of these two zygomatic arch bones to total zygomatic arch length. Candidate genes in this region were identified and real-time PCR of the maxillary processes of DO founder strain embryos indicated differences in the RNA expression levels for two of the candidate genes, Camkmt and Six2.
Conclusions:
A genomic region underlying negative pleiotropy of two zygomatic arch bones was identified, which provides a mechanism for antagonism in component bone lengths while constraining overall zygomatic arch length. This type of mechanism may have led to variation in the contribution of individual bones to the zygomatic arch noted across mammals. Given that similar genetic and developmental mechanisms may underlie negative correlations in other parts of the skull, these results provide an important step toward understanding the developmental basis of evolutionary variation and constraint in skull morphology.
Objectives:
Morphological integration, or the tendency for covariation, is commonly seen in complex traits such as the human face. The effects of growth on shape, or allometry, represent a ubiquitous but poorly understood axis of integration. We address the question of to what extent age and measures of size converge on a single pattern of allometry for human facial shape.
Methods:
Our study is based on two large cross-sectional cohorts of children, one from Tanzania and the other from the United States (N = 7,173). We employ 3D facial imaging and geometric morphometrics to relate facial shape to age and anthropometric measures.
Results:
The two populations differ significantly in facial shape, but the magnitude of this difference is small relative to the variation within each group. Allometric variation for facial shape is similar in both populations, representing a small but significant proportion of total variation in facial shape. Different measures of size are associated with overlapping but statistically distinct aspects of shape variation. Only half of the size-related variation in facial shape can be explained by the first principal component of four size measures and age while the remainder associates distinctly with individual measures.
Conclusions:
Allometric variation in the human face is complex and should not be regarded as a singular effect. This finding has important implications for how size is treated in studies of human facial shape and for the developmental basis for allometric variation more generally.
Morphological traits can be highly variable over time in a particular geographical area. Different selective pressures shape those traits, which is crucial in evolutionary biology. Among these traits, insect wing morphometry has already been widely used to describe phenotypic variability at the inter-specific level. On the contrary, fewer studies have focused on intra-specific wing morphometric variability. Yet, such investigations are relevant to study potential convergences of variation that could highlight micro-evolutionary processes. The recent sampling and sequencing of three solitary bees of the genus Melitta across their entire species range provides an excellent opportunity to jointly analyse genetic and morphometric variability. In the present study, we first aim to analyse the spatial distribution of the wing shape and centroid size (used as a proxy for body size) variability. Secondly, we aim to test different potential predictors of this variability at both the intra- and inter-population
The human face is an array of variable physical features that together make each of us unique and distinguishable. Striking familial facial similarities underscore a genetic component, but little is known of the genes that underlie facial shape differences. Numerous studies have estimated facial shape heritability using various methods. Here, we used advanced 3D imaging technology and quantitative human genetics analysis to estimate narrow-sense heritability, heritability explained by common genetic variation, and pairwise genetic correlations of 38 measures of facial shape and size in normal African Bantu children from Tanzania. Specifically, we fit a linear mixed model of genetic relatedness between close and distant relatives to jointly estimate variance components that correspond to heritability explained by genomewide common genetic variation and variance explained by uncaptured genetic variation, the sum representing total narrow sense heritability. Our significant estimates for narrow sense heritability of specific facial traits range from 28% - 67%, with horizontal measures being slightly more heritable than vertical or depth measures. Furthermore, for over half of facial traits >90% of narrow-sense heritability can be explained by common genetic variation. We also find high absolute genetic correlation between most traits, indicating large overlap in underlying genetic loci. Not surprisingly, traits measured in the same physical orientation (i.e., both horizontal or both vertical) have high positive genetic correlations, whereas traits in opposite orientations have high negative correlations. The complex genetic architecture of facial shape informs our understanding of the intricate relationships among different facial features as well as overall facial development.
The naked mole-rat (NMR) is the longest-lived rodent with a maximum lifespan >31 years. Intriguingly, fully-grown naked mole-rats (NMRs) exhibit many traits typical of neonatal rodents. However, little is known about NMR growth and maturation, and we question whether sustained neotenous features when compared to mice, reflect an extended developmental period, commensurate with their exceptionally long life. We tracked development from birth to 3 years of age in the slowest maturing organ, the brain, by measuring mass, neural stem cell proliferation, axonal, and dendritic maturation, synaptogenesis and myelination. NMR brain maturation was compared to data from similar sized rodents, mice, and to that of long-lived mammals, humans, and non-human primates. We found that at birth, NMR brains are significantly more developed than mice, and rather are more similar to those of newborn primates, with clearly laminated hippocampi and myelinated white matter tracts. Despite this more mature brain at birth than mice, postnatal NMR brain maturation occurs at a far slower rate than mice, taking four-times longer than required for mice to fully complete brain development. At 4 months of age, NMR brains reach 90% of adult size with stable neuronal cytostructural protein expression whereas myelin protein expression does not plateau until 9 months of age in NMRs, and synaptic protein expression continues to change throughout the first 3 years of life. Intriguingly, NMR axonal composition is more similar to humans than mice whereby NMRs maintain expression of three-repeat (3R) tau even after brain growth is complete; mice experience an abrupt downregulation of 3R tau by postnatal day 8 which continues to diminish through 6 weeks of age. We have identified key ages in NMR cerebral development and suggest that the long-lived NMR may provide neurobiologists an exceptional model to study brain developmental processes that are compressed in common short-lived laboratory animal models.
The human face is a complex assemblage of highly variable yet clearly heritable anatomic structures that together make each of us unique, distinguishable, and recognizable. Relatively little is known about the genetic underpinnings of normal human facial variation. To address this, we carried out a large genomewide association study and two independent replication studies of Bantu African children and adolescents from Mwanza, Tanzania, a region that is both genetically and environmentally relatively homogeneous. We tested for genetic association of facial shape and size phenotypes derived from 3D imaging and automated landmarking of standard facial morphometric points. SNPs within genes SCHIP1 and PDE8A were associated with measures of facial size in both the GWAS and replication cohorts and passed a stringent genomewide significance threshold adjusted for multiple testing of 34 correlated traits. For both SCHIP1 and PDE8A, we demonstrated clear expression in the developing mouse face by both whole-mount in situ hybridization and RNA-seq, supporting their involvement in facial morphogenesis. Ten additional loci demonstrated suggestive association with various measures of facial shape. Our findings, which differ from those in previous studies of European-derived whites, augment understanding of the genetic basis of normal facial development, and provide insights relevant to both human disease and forensics.
C57BL/6J is one of the most commonly used inbred mouse strains in biomedical research, including studies of craniofacial development and teratogenic studies of craniofacial malformation. The current study quantitatively assessed the development of the skull in male C57BL/6J mice by using high-resolution 3D imaging of 55 landmarks from 48 male mice over 10 developmental time points from postnatal day 0 to 90. The growth of the skull plateaued at approximately postnatal day 60, and the shape of the skull did not change markedly thereafter. The amount of asymmetry in the craniofacial skeleton seemed to peak at birth, but considerable variation persisted in all age groups. For C57BL/6J male mice, postnatal day 60 is the earliest time point at which the skull achieves its adult shape and proportions. In addition, C57BL/6J male mice appear to have an inherent susceptibility to craniofacial malformation. ©2016 by the American Association for Laboratory Animal Science.
Allometry refers to the size-related changes of morphological traits and remains an essential concept for the study of evolution and development. This review is the first systematic comparison of allometric methods in the context of geometric morphometrics that considers the structure of morphological spaces and their implications for characterizing allometry and performing size correction. The distinction of two main schools of thought is useful for understanding the differences and relationships between alternative methods for studying allometry. The Gould-Mosimann school defines allometry as the covariation of shape with size. This concept of allometry is implemented in geometric morphometrics through the multivariate regression of shape variables on a measure of size. In the Huxley-Jolicoeur school, allometry is the covariation among morphological features that all contain size information. In this framework, allometric trajectories are characterized by the first principal component, which is a line of best fit to the data points. In geometric morphometrics, this concept is implemented in analyses using either Procrustes form space or conformation space (the latter also known as size-and-shape space). Whereas these spaces differ substantially in their global structure, there are also close connections in their localized geometry. For the model of small isotropic variation of landmark positions, they are equivalent up to scaling. The methods differ in their emphasis and thus provide investigators with flexible tools to address specific questions concerning evolution and development, but all frameworks are logically compatible with each other and therefore unlikely to yield contradictory results.
Mechanisms of resource allocation are essential for maternal and fetal survival, particularly when the availability of nutrients is limited. We investigated the responses of feto-placental development to maternal chronic protein malnutrition to test the hypothesis that maternal low protein diet produces differential growth restriction of placental and fetal tissues, and adaptive changes in the placenta that may mitigate impacts on fetal growth. C57BL/6J female mice were fed either a low-protein diet (6% protein) or control isocaloric diet (20% protein). On embryonic days E10.5, 17.5 and 18.5 tissue samples were prepared for morphometric, histological and quantitative RT-PCR analyses, which included markers of trophoblast cell subtypes. Potential endocrine adaptations were assessed by the expression of Prolactin-related hormone genes. In the low protein group, placenta weight was significantly lower at E10.5, followed by reduction of maternal weight at E17.5, while the fetuses became significantly lighter no earlier than at E18.5. Fetal head at E18.5 in the low protein group, though smaller than controls, was larger than expected for body size. The relative size and shape of the cranial vault and the flexion of the cranial base was affected by E17.5 and more severely by E18.5. The junctional zone, a placenta layer rich in endocrine and energy storing glycogen cells, was smaller in low protein placentas as well as the expression of Pcdh12, a marker of glycogen trophoblast cells. Placental hormone gene Prl3a1 was altered in response to low protein diet: expression was elevated at E17.5 when fetuses were still growing normally, but dropped sharply by E18.5 in parallel with the slowing of fetal growth. This model suggests that nutrients are preferentially allocated to sustain fetal and brain growth and suggests the placenta as a nutrient sensor in early gestation with a role in mitigating impacts of poor maternal nutrition on fetal growth.
With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size-with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for more than 70% of genetic variation present in all the 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or non-additive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map has important consequences for gene identification and may shed light on the evolvability of organisms.
Growth of the craniofacial skeleton is a complex process controlled by both genetic and epigenetic factors, perturbations of which can lead to varying degrees of dysmorphology. Mouse models that recapitulate clinical craniofacial phenotypes are instrumental in studying the morphogenetic progression of diseases as well as uncovering their genetic and molecular bases. Commonly encountered phenotypes in these models include defects in the cranial base synchondroses, calvarial sutures, mandible or the midface, or any combination thereof, with the concurrent presence of altered overall craniofacial growth. However, the literature lacks an adequate normative timeline of developmental events and growth trends that shape the mouse craniofacial skeleton. In this report, we analyzed the postnatal craniofacial ontogeny (from postnatal day 7 [P7] through to P112) of male mice from the most widely used inbred mouse strain, C57BL/6J, using high-resolution microcomputed tomography (μCT) in combination with classic morphometric approaches. We also evaluated cranial base synchondroses at the histological level, and compared it to μCT-generated data to assess the timing and pattern of closure of these structures. Our data underscore the complex and unique growth patterns of individual bones and cranial regions and highlight the need to include younger animals in studies aimed at analyzing craniofacial growth processes. Furthermore, these data serve as a reference standard for future quantitative work.
Adult body size in animals is determined by the duration of the growth period and the amount of mass gained during that period. Few models of body size regulation distinguish between these two components or explicitly address the mechanisms that control the duration of the growth period. Body size in the tobacco hornworm Manduca sexia is controlled by three underlying physiological factors: growth rate; timing of the onset of juvenile hormone decay (which initiates the processes leading to pupation), as measured by the critical weight; and the timing of prothoracicotropic hormone (PTTH, which stimulates ecdysteroid secretion) and ecdysteroid secretion, as measured by the interval to cessation of growth (ICG, the time interval between the attainment of the critical weight and entry into the pre-pupal wandering stage). The critical weight and the ICG determine the duration of the growth period, while growth rate determines how much mass accumulates during that period. We studied how phenotypic plasticity of body size in M. sexia, in response to variation in temperature and diet quality, is affected by phenotypic plasticity of these three physiological determinants of body size. We show that plasticity of size in response to diet quality is regulated by variation in growth rate and critical weight, while plasticity of size in response to temperature is regulated by variation in growth rate and the ICG. These results demonstrate the importance of the timing of hormonal events in the regulation of phenotypic plasticity. We suggest that the differential sensitivity of the physiological processes that regulate body size may enable insects to adjust adult body size in response to simultaneous variation in multiple types of environmental stimuli.
Morphological allometry refers to patterns of covariance between body parts resulting from variation in body size. Whether measured during growth (ontogenetic allometry), among individuals at similar developmental stage (static allometry), or among populations or species (evolutionary allometry), allometric relationships are often tight and relatively invariant. Consequently, it has been suggested that allometries have low evolvability and could constrain phenotypic evolution by forcing evolving species along fixed trajectories. Alternatively, allometric relationships may result from natural selection for functional optimization. Despite nearly a century of active research, distinguishing between these alternatives remains difficult, partly due to wide differences in the meaning assigned to the term allometry. In particular, a broad use of the term, encompassing any monotonic relationship between body parts, has become common. This usage breaks the connection to the proportional growth regulation that motivated Huxley's original narrow-sense use of allometry to refer to power-law relationships between traits. Focusing on the narrow-sense definition of allometry, we review here evidence for and against the allometry-as-a-constraint hypothesis. Although the low evolvability and the evolutionary invariance of the static allometric slope observed in some studies suggest a possible constraining effect of this parameter on phenotypic evolution, the lack of knowledge about selection on allometry prevents firm conclusions.
Mice reproduce many features of human pregnancy and have been widely used to model disorders of pregnancy. However, it has not been known whether fetal mice reproduce the physiologic response to hypoxia known as brain sparing, where blood flow is redistributed to preserve oxygenation of the brain at the expense of other fetal organs. In the present study, blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and Doppler ultrasound were used to determine the effect of acute hypoxia on the fetal blood flow in healthy, pregnant mice. As the maternal inspired gas mixture was varied between 100% and 8% oxygen on the timescale of minutes, the BOLD signal intensity decreased by 44±18% in the fetal liver and by 12±7% in the fetal brain. Using Doppler ultrasound measurements, mean cerebral blood velocity was observed to rise by 15±8% under hypoxic conditions relative to hyperoxia. These findings are consistent with active regulation of cerebral oxygenation and clearly show brain sparing in fetal mice.Journal of Cerebral Blood Flow & Metabolism advance online publication, 9 April 2014; doi:10.1038/jcbfm.2014.62.
Morphological traits often covary within and among species according to simple power laws referred to as allometry. Such allometric relationships may result from common growth regulation, and this has given rise to the hypothesis that allometric exponents may have low evolvability and constrain trait evolution. We formalize hypotheses for how allometry may constrain morphological trait evolution across taxa, and test these using more than three-hundred empirical estimates of static (within-species) allometric relations of animal morphological traits. Although we find evidence for evolutionary changes in allometric parameters on million-year, cross-species time scales, there is limited evidence for microevolutionary changes in allometric slopes. Accordingly, we find that static allometries often predict evolutionary allometries on the subspecies level, but less so across species. Although there is a large body of work on allometry in a broad sense that includes all kinds of morphological trait-size relationships, we found relatively little information about the evolution of allometry in the narrow sense of a power relationship. Despite the many claims of microevolutionary changes of static allometries in the literature, hardly any of these apply to narrow-sense allometry, and we argue that the hypothesis of strongly constrained static allometric slopes remains viable. This article is protected by copyright. All rights reserved.
Intrauterine growth restriction (IUGR) is associated with perinatal morbidity and mortality. IUGR is defined as fetus that fails to achieve his growth potential. Antenatal small for gestational age (SGA) is defined as fetus with weight <10th percentile. IUGR and SGA are commonly used interchangeably. The identification of IUGR is important. IUGR identification begins with assessment of risk factor(s), and the diagnosis is made by ultrasound using biometry when this confirms an estimated fetal weight (EFW) of <10th percentile. The common risk factors include maternal causes (hypertension, diabetes, cardiopulmonary disease, anemia, malnutrition, smoking, drug use), fetal causes (genetic disease including aneuploidy, congenital malformations, fetal infection, multiple pregnancies), and placental causes (placental insufficiency, placental infarction, placental mosaicism). Intrauterine growth determines the perinatal, postnatal, and adult life development. IUGR is associated with increased risk of development in adult life of metabolic diseases including but not limited to hypertension, diabetes, obesity, dyslipidemia, and the metabolic syndrome.
Divergence of serially homologous elements of organisms is a common evolutionary pattern contributing to increased phenotypic complexity. Here we study the genomic intervals affecting the variational independence of fore- and hind limb traits within an experimental mouse population. We use an advanced intercross of inbred mouse strains to map the loci associated with the degree of autonomy between fore and hind limb long bone lengths (loci affecting the relationship between traits, relationship QTL or rQTL). These loci have been proposed to interact locally with the products of pleiotropic genes, thereby freeing the local trait from the variational constraint due to pleiotropic mutations. Using the known polymorphisms (SNP) between the parental strains, we characterized and compared the genomic regions in which the relationship QTL, as well as their interaction partners (intQTL), reside. We find that these two classes of QTL intervals harbor different kinds of molecular variation. SNPs in rQTL intervals more frequently reside in limb-specific cis-regulatory regions than SNPs in intQTL intervals. The intQTL loci modified by the rQTL, in contrast, show the signature of protein coding variation. This result is consistent with the widely accepted view that protein-coding mutations have broader pleiotropic effects than cis-regulatory polymorphisms. For both types of QTL intervals the underlying candidate genes are enriched for genes involved in protein binding. This finding suggests that rQTL effects are caused by local interactions among the products of the causal genes harbored in rQTL and intQTL intervals. This is the first study to systematically document the population-level molecular variation underlying the evolution of character individuation.
Facial length is one of the best known examples of heterochrony. Changes in the timing of facial growth have been invoked as a mechanism for the origin of our short human face from our long-faced extinct relatives. Such heterochronic changes arguably permit great evolutionary flexibility, allowing the mammalian face to be remodelled simply by modifying postnatal growth. Here we present new data that show that this mechanism is significantly constrained by adult size. Small mammals are more brachycephalic (short faced) than large ones, despite the putative independence between adult size and facial length. This pattern holds across four phenotypic lineages: antelopes, fruit bats, tree squirrels and mongooses. Despite the apparent flexibility of facial heterochrony, growth of the face is linked to absolute size and introduces what seems to be a loose but clade-wide mammalian constraint on head shape.
We briefly and informally review the concepts of size, shape, and form and how they are estimated in geometric morphometrics using Procrustes analysis. We demonstrate how deformation grids and reconstructed shapes or forms can be used as powerful tools to visualize shape and form differ- ences. Complex patterns of individual or group differences can be studied effectively by ordinations of shape space or form space. Allometry, the statistical relationship between size and shape, is es- timated in geometric morphometrics by regression of the Procrustes shape coordinates on centroid size. We illustrate these methods by an application to human face shape. We reveal shape cues to body size in the adult male face, partly resembling ontogenetic allometry. Facial allometry might thus be an important confounding factor in studies of face perception and human mate choice.
Synopsis. Allometry designates the changes in relative dimensions of parts of the body that are correlated with changes in overall size. Julian Huxley and Georges Teissier coined this term in 1936. In a joint paper, they agreed to use this term in order to avoid confusion in the field of relative growth. They also agreed on the conventional symbols to use in the algebraic formula: y = bxα. Julian Huxley is often said to have discovered the “law of constant differential growth” in 1924, but a similar formula had been used earlier by several authors, in various contexts, and under various titles. Three decades before Huxley, Dubois and Lapicque used a power law and logarithmic coordinates for the description of the relation between brain size and body size in mammals, both from an intraspecific, and an interspecific, point of view. Later on, in the 1910s and early 1920s, Pézard and Champy's work on sexual characters provided decisive experimental evidence in favor of a law of relative growth at the level of individual development.
This paper examines: (1) early works on relative growth, and their relation to Huxley and Teissier's “discovery”; (2) Teissier and Huxley's joint paper of 1936, in particular their tacit disagreement on the signification of the coefficient “b”; and (3) the status of allometry in evolutionary theory after Huxley, especially in the context of paleobiology.
Quantitative genetic theory predicts that functionally and developmentally related characters will be morphologically integrated and tend to be inherited together. Furthermore, coinheritance and environmental integration of functionally related characters may be important in facilitating adaptive evolution. The hypothesis that functionally and developmentally related features of the cranium are phenotypically, genetically, and environmentally integrated in the saddle-back tamarin (Saguinus fuscicollis) cranium is tested. Thirty-nine craniofacial measurements were taken on 209 animals from the Oak Ridge Associated Universities' Marmoset Research Center. Heritabilities and phenotypic, genetic, and environmental correlations were calculated using maximum likelihood methods after the data were corrected for sex and specified environmental effects. The correlation matrices were compared to a series of theoretical intertrait connectivities representing expected patterns of morphological integration using Mantel's test. The patterns of phenotypic, genetic, and environmental correlation among craniofacial traits matched patterns predicted on the basis of developmental and functional relationships among cranial traits. The similarity between functional and developmental integration and correlation was largely due to the relatively high correlations among cranial vault traits and among oral traits. Both genetic and environmental correlation among developmentally and functionally related characters may enhance the rate of evolutionary change.
The Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multi parental recombinant inbred panel derived from eight laboratory mouse inbred strains. Breeding of the CC lines was initiated at multiple international sites using mice from The Jackson Laboratory. Currently, this innovative project is breeding independent CC lines at the University of North Carolina (UNC), at Tel Aviv University (TAU), and at Geniad in Western Australia (GND). These institutions aim to make publicly available the completed CC lines and their genotypes and sequence information. We genotyped, and report here, results from 458 extant lines from UNC, TAU, and GND using a custom genotyping array with 7500 SNPs designed to be maximally informative in the CC and used a novel algorithm to infer inherited haplotypes directly from hybridization intensity patterns. We identified lines with breeding errors and cousin lines generated by splitting incipient lines into two or more cousin lines at early generations of inbreeding. We then characterized the genome architecture of 350 genetically independent CC lines. Results showed that founder haplotypes are inherited at the expected frequency, although we also consistently observed highly significant transmission ratio distortion at specific loci across all three populations. On chromosome 2, there is significant overrepresentation of WSB/EiJ alleles, and on chromosome X, there is a large deficit of CC lines with CAST/EiJ alleles. Linkage disequilibrium decays as expected and we saw no evidence of gametic disequilibrium in the CC population as a whole or in random subsets of the population. Gametic equilibrium in the CC population is in marked contrast to the gametic disequilibrium present in a large panel of classical inbred strains. Finally, we discuss access to the CC population and to the associated raw data describing the genetic structure of individual lines. Integration of rich phenotypic and genomic data over time and across a wide variety of fields will be vital to delivering on one of the key attributes of the CC, a common genetic reference platform for identifying causative variants and genetic networks determining traits in mammals.
Organisms represent a complex arrangement of anatomical structures and individuated parts that must maintain functional associations through development. This integration of variation between functionally related body parts and the modular organization of development are fundamental determinants of their evolvability. This is because integration results in the expression of coordinated variation that can create preferred directions for evolutionary change, while modularity enables variation in a group of traits or regions to accumulate without deleterious effects on other aspects of the organism. Using our own work on both model systems (e.g., lab mice, avians) and natural populations of rodents and primates, we explore in this paper the relationship between patterns of phenotypic covariation and the developmental determinants of integration that those patterns are assumed to reflect. We show that integration cannot be reliably studied through phenotypic covariance patterns alone and argue that the relationship between phenotypic covariation and integration is obscured in two ways. One is the superimposition of multiple determinants of covariance in complex systems and the other is the dependence of covariation structure on variances in covariance-generating processes. As a consequence, we argue that the direct study of the developmental determinants of integration in model systems is necessary to fully interpret patterns of covariation in natural populations, to link covariation patterns to the processes that generate them, and to understand their significance for evolutionary explanation.
The estimation of genetic correlations is central to the study of evolutionary change in populations. However, sample sizes required to achieve a small standard error are typically enormous. This precludes large-scale comparative analyses. Cheverud has conjectured that in some circumstances the phenotypic correlation can be substituted for the genetic correlation. This suggestion is examined using a large set of morphological traits in the sand cricket, Gryllus firmus. In this case the difference between the two estimates is very small. Further, by simulation it is shown that the phenotypic correlations are as good as, or better than, the estimated genetic correlations as estimates of the true genetic correlations. Examination of other data sets of morphological traits suggests that the phenotypic correlation may, in general, be a suitable substitute for the estimated genetic correlation. However, because the number of such examinations is still small, a protocol is suggested in which two sets of genetic analyses are undertaken to confirm the assumption in a large comparative analysis.Keywords: bias, evolution, genetic correlation, Pearson product-moment correlation, phenotypic correlation
The Diversity Outbred (DO) population is a heterogeneous stock derived from the same eight founder strains as the Collaborative Cross (CC) inbred strains. Genetically heterogeneous DO mice display a broad range of phenotypes. Natural levels of heterozygosity provide genetic buffering and, as a result, DO mice are robust and breed well. Genetic mapping analysis in the DO presents new challenges and opportunities. Specialized algorithms are required to reconstruct haplotypes from high-density SNP array data. The eight founder haplotypes can be combined into 36 possible diplotypes, which must be accommodated in QTL mapping analysis. Population structure of the DO must be taken into account here. Estimated allele effects of eight founder haplotypes provide information that is not available in two-parent crosses and can dramatically reduce the number of candidate loci. Allele effects can also distinguish chance colocation of QTL from pleiotropy, which provides a basis for establishing causality in expression QTL studies. We recommended sample sizes of 200-800 mice for QTL mapping studies, larger than for traditional crosses. The CC inbred strains provide a resource for independent validation of DO mapping results. Genetic heterogeneity of the DO can provide a powerful advantage in our ability to generalize conclusions to other genetically diverse populations. Genetic diversity can also help to avoid the pitfall of identifying an idiosyncratic reaction that occurs only in a limited genetic context. Informatics tools and data resources associated with the CC, the DO, and their founder strains are developing rapidly. We anticipate a flood of new results to follow as our community begins to adopt and utilize these new genetic resource populations.
We develop an approach to risk classification based on quantile contours and allometric modelling of multivariate anthropometric measurements. We propose the definition of allometric direction tangent to the directional quantile envelope, which divides ratios of measurements into half-spaces. This in turn provides an operational definition of directional quantile that can be used as cutoff for risk assessment. We show the application of the proposed approach using a large dataset from the Vermont Oxford Network containing observations of birthweight (BW) and head circumference (HC) for more than 150,000 preterm infants. Our analysis suggests that disproportionately growth-restricted infants with a larger HC-to-BW ratio are at increased mortality risk as compared to proportionately growth-restricted infants. The role of maternal hypertension is also investigated.
Variation in the shape of the human face and in stature is determined by complex interactions between genetic and environmental influences. One such environmental influence is malnourishment, which can result in growth faltering, usually diagnosed by means of comparing an individual's stature with a set of age-appropriate standards. These standards for stature, however, are typically ascertained in groups where people are at low risk for growth faltering. Moreover, genetic differences among populations with respect to stature are well established, further complicating the generalizability of stature-based diagnostic tools. In a large sample of children aged 5–19 years, we obtained high-resolution genomic data, anthropometric measures and 3D facial images from individuals within and around the city of Mwanza, Tanzania. With genome-wide complex trait analysis, we partitioned genetic and environmental variance for growth outcomes and facial shape. We found that children with growth faltering have faces that look like those of older and taller children, in a direction opposite to the expected allometric trajectory, and in ways predicted by the environmental portion of covariance at the community and individual levels. The environmental variance for facial shape varied subtly but significantly among communities, whereas genetic differences were minimal. These results reveal that facial shape preserves information about exposure to undernourishment, with important implications for refining assessments of nutritional status in children and the developmental-genetics of craniofacial variation alike.
Genetic variances and correlations lie at the center of quantitative evolutionary theory. They are often difficult to estimate, however, due to the large samples of related individuals that are required. I investigated the relationship of genetic- and phenotypic-correlation magnitudes and patterns in 41 pairs of matrices drawn from the literature in order to determine their degree of similarity and whether phenotypic parameters could be used in place of their genetic counterparts in situations where genetic variances and correlations cannot be precisely estimated. The analysis indicates that squared genetic correlations were on average much higher than squared phenotypic correlations and that genetic and phenotypic correlations had only broadly similar patterns. These results could be due either to biological causes or to imprecision of genetic-correlation estimates due to sampling error. When only those studies based on the largest sample sizes (effective sample size of 40 or more) were included, squared genetic-correlation estimates were only slightly greater than their phenotypic counterparts and the patterns of correlation were strikingly similar. Thus, much of the dissimilarity between phenotypic- and genetic-correlation estimates seems to be due to imprecise estimates of genetic correlations. Phenotypic correlations are likely to be fair estimates of their genetic counterparts in many situations. These further results also indicate that genetic and environmental causes of phenotypic variation tend to act on growth and development in a similar manner.
The relationship between organ and body size, known as morphological allometry, has fascinated biologists for over a century because changes in allometry generate the vast diversity of organism shapes. Nevertheless, progress has been limited in understanding the genetic mechanisms that regulate allometries and how these mechanisms evolve. This is perhaps because allometry is measured at the population level, however adult organ and body size depends on genetic background and the developmental environment of individuals. Recent findings have enhanced our understanding of how insects regulate their organ and body sizes in response to environmental conditions, particularly nutritional availability. We argue that merging these developmental insights with a population genetics approach will provide a powerful system for understanding the evolution of allometry.
Using eight inbred founder strains of the mouse Collaborative Cross (CC) project and their reciprocal F1 hybrids, we quantified variation in craniofacial morphology across mouse strains, explored genetic contributions to craniofacial variation that distinguish the founder strains, and tested whether specific or summary measures of craniofacial shape display stronger additive genetic contributions. This study thus provides critical information about phenotypic diversity among CC founder strains and about the genetic contributions to this phenotypic diversity, which is relevant to understanding the basis of variation in standard laboratory strains and natural populations. Craniofacial shape was quantified as a series of size-adjusted linear dimensions (RDs) and by principal components (PC) analysis of morphological landmarks captured from computed tomography images from 62 of the 64 reciprocal crosses of the CC founder strains. We first identified aspects of skull morphology that vary between these phenotypically 'normal' founder strains and that are defining characteristics of these strains. We estimated the contributions of additive and various non-additive genetic factors to phenotypic variation using diallel analyses of a subset of these strongly differing RDs and the first eight PCs of skull shape variation. We find little difference in the genetic contributions to RD measures and PC scores, suggesting fundamental similarities in the magnitude of genetic contributions to both specific and summary measures of craniofacial phenotypes. Our results indicate that there are stronger additive genetic effects associated with defining phenotypic characteristics of specific founder strains, suggesting these distinguishing measures are good candidates for use in genotype-phenotype association studies of CC mice. Our results add significantly to understanding of genotype-phenotype associations in the skull, which serve as a foundation for modeling the origins of medically and evolutionarily relevant variation.
Regional differences in modern human facial features are present at birth, and ontogenetic allometry contributes to variation in adults. However, details regarding differential rates of growth and timing among regional groups are lacking. We explore ontogenetic and static allometry in a cross-sectional sample spanning Africa, Europe and North America, and evaluate tempo and mode in two regional groups with very different adult facial morphology, the Khoisan and Inuit.
Semilandmark geometric morphometric methods, multivariate statistics and growth simulations were used to quantify and compare patterns of facial growth and development.
Regional-specific facial morphology develops early in ontogeny. The Inuit has the most distinct morphology and exhibits heterochronic differences in development compared to other regional groups. Allometric patterns differ during early postnatal development, when significant increases in size are coupled with large amounts of shape changes. All regional groups share a common adult static allometric trajectory, which can be attributed to sexual dimorphism, and the corresponding allometric shape changes resemble developmental patterns during later ontogeny.
The amount and pattern of growth and development may not be shared between regional groups, indicating that a certain degree of flexibility is allowed for in order to achieve adult size. In early postnatal development the face is less constrained compared to other parts of the cranium allowing for greater evolvability. The early development of region-specific facial features combined with heterochronic differences in timing or rate of growth, reflected in differences in facial size, suggest different patterns of postnatal growth. Am J Phys Anthropol, 2015. © 2015 Wiley Periodicals, Inc.
© 2015 Wiley Periodicals, Inc.