Cranial modularity and sequence heterochrony in mammals

Heterochrony, the temporal shifting of developmental events relative to each other, requires a degree of autonomy among those processes or structures. Modularity, the division of larger structures or processes into autonomous sets of internally integrated units, is often discussed in relation to the concept of heterochrony. However, the relationship between the developmental modules derived from studies of heterochrony and evolutionary modules, which should be of adaptive importance and relate to the genotype-phenotype map, has not been explicitly studied. I analyzed a series of sectioned and whole cleared-and-stained embryological and neonatal specimens, supplemented with published ontogenetic data, to test the hypothesis that bones within the same phenotypic modules, as determined by morphometric analysis, are developmentally integrated and will display coordinated heterochronic shifts across taxa. Modularity was analyzed in cranial bone ossification sequences of 12 therian mammals. A dataset of 12-18 developmental events was used to assess if modularity in developmental sequences corresponds to six phenotypic modules, derived from a recent morphometric analysis of cranial modularity in mammals. Kendall's tau was used to measure rank correlations, with randomization tests for significance. If modularity in developmental sequences corresponds to observed phenotypic modules, bones within a single phenotypic module should show integration of developmental timing, maintaining the same timing of ossification relative to each other, despite differences in overall ossification sequences across taxa. Analyses did not find any significant conservation of developmental timing within the six phenotypic modules, meaning that bones that are highly integrated in adult morphology are not significantly integrated in developmental timing.     

Mosaic evolution,preadaptation, and the evolution of evolvability in apes

A major goal in postsynthesis evolutionary biology has been to better understand how complex interactions between traits drive movement along and facilitate the formation of distinct evolutionary pathways. I present analyses of a character matrix sampled across the haplorrhine skeleton that revealed several modules of characters displaying distinct patterns in macroevolutionary disparity. Comparison of these patterns to those in neurological development showed that early ape evolution was characterized by an intense regime of evolutionary and developmental flexibility. Shifting and reduced constraint in apes was met with episodic bursts in phenotypic innovation that built a wide array of functional diversity over a foundation of shared developmental and anatomical structure. Shifts in modularity drove dramatic evolutionary changes across the ape body plan in two distinct ways: (1) an episode of relaxed integration early in hominoid evolution coincided with bursts in evolutionary rate across multiple character suites; (2) the formation of two new trait modules along the branch leading to chimps and humans preceded rapid and dramatic evolutionary shifts in the carpus and pelvis. Changes to the structure of evolutionary mosaicism may correspond to enhanced evolvability that has a “preadaptive” effect by catalyzing later episodes of dramatic morphological remodeling.     

Evolution of the Mammalian Neck from Developmental,Morpho-Functional,and Paleontological Perspectives

The mammalian neck adopts a variety of postures during daily life and generates numerous head trajectories. Despite its functional diversity, the neck is constrained to seven cervical vertebrae in (almost) all mammals. Given this low number, an unexpectedly high degree of modularity of the mammalian neck has more recently been uncovered. This work aims to review neck modularity in mammals from a developmental, morpho-functional, and paleontological perspective and how high functional diversity evolved in the mammalian neck after the occurrence of meristic limitations. The fixed number of cervical vertebrae and the developmental modularity of the mammalian neck are closely linked to anterior Hox genes expression and strong developmental integration between the neck and other body regions. In addition, basic neck biomechanics promote morpho-functional modularity due to preferred motion axes in the cranio-cervical and cervico-thoracic junction. These developmental and biomechanical determinants result in the characteristic and highly conserved shape variation among the vertebrae that delimits morphological modules. The step-wise acquisition of these unique cervical traits can be traced in the fossil record. The increasing functional specialization of neck modules, however, did not evolve all at once but started much earlier in the upper than in the lower neck. Overall, the strongly conserved modularity in the mammalian neck represents an evolutionary trade-off between the meristic constraints and functional diversity. Although a morpho-functional partition of the neck is common among amniotes, the degree of modularity and the way neck disparity is realized is unique in mammals.

     

Modularity as a source of new morphological variation in the mandible of hybrid mice

ABSTRACT: BACKGROUND: Hybridization is often seen as a process dampening phenotypic differences accumulated between diverging evolutionary units. For a complex trait comprising several relatively independent modules, hybridization may however simply generate new phenotypes, by combining into a new mosaic modules inherited from each parental groups and parts intermediate with respect to the parental groups. We tested this hypothesis by studying mandible size and shape in a set of first and second generation hybrids resulting from inbred wild-derived laboratory strains documenting two subspecies of house mice, Musmusculusdomesticus and Musmusculusmusculus. Phenotypic variation of the mandible was divided into nested partitions of developmental, evolutionary and functional modules. RESULTS: The size and shape of the modules were differently influenced by hybridization. Some modules seemed to be the result of typical additive effects with hybrids intermediate between parents, some displayed a pattern expected in the case of monogenic dominance, whereas in other modules, hybrids were transgressive. The result is interpreted as the production of novel mandible morphologies. Beyond this modularity, modules in functional interaction tended to display significant covariations. CONCLUSIONS: Modularity emerges as a source of novel morphological variation by its simple potential to combine different parts of the parental phenotypes into a novel offspring mosaic of modules. This effect is partly counterbalanced by bone remodeling insuring an integration of the mosaic mandible into a functional ensemble, adding a non-genetic component to the production of transgressive phenotypes in hybrids.     

The integrated phenotype

Proper functioning of complex phenotypes requires that multiple traits work together. Examination of relationships among traits within and between complex characters and how they interact to function as a whole organism is critical to advancing our understanding of evolutionary developmental plasticity. Phenotypic integration refers to the relationships among multiple characters of a complex phenotype, and their relationships with other functional units (modules) in an organism. In this review, I summarize a brief history of the concept of phenotypic integration in plant and animal biology. Following an introduction of concepts, including modularity, I use an empirical case-study approach to highlight recent advance in clarifying the developmental and genomic basis of integration. I end by highlighting some novel approaches to genomic and epigenetic perturbations that offer promise in further addressing the role of phenotypic integration in evolutionary diversification. In the age of the phenotype, studies that examine the genomic and developmental changes in relationships of traits across environments will shape the next chapter in our quest for understanding the evolution of complex characters.     

DISSECTION OF EVOLUTIONARY NETWORKS TO ASSESS THEIR ROLE IN THE EVOLUTION OF ROBUSTNESS,FUNCTION, AND DIVERSIFICATION

Biological systems are remarkably robust in the face of environmental, mutational, and developmental perturbations. Analyses of molecular networks reveal recurrent features, such as modularity, that have been implicated in robustness and evolvability. Multiple theoretical models account for these features, yet few empirical tests of these models exist. Here I develop a set of broadly applicable methodologies to enable expanded empirical evaluation of model predictions. The methodologies focus on the inference and analysis of networks that depict evolutionary correlations among characters. I apply these methodologies to analyze an evolutionary network at a larger scale of organization among 42 stem anatomical and morphological characters of 52 species in the genus Adenia (Passifloraceae). I evaluate a model predicting that modular evolutionary networks will evolve in response to environmental change. The evolutionary network of Adenia is modular and “small‐world,” and the three diagnosed modules correspond roughly to functions of transport, storage, and mechanical support. The phylogenetically informed analyses suggest that the storage module is more impacted by environmental change than expected by chance. These results corroborate the hypothesis that modularity reduces the impact of environmental change, but this result requires further empirical evaluation that can be aided by the proposed methods in additional study systems.     

Cranial modularity shifts during mammalian evolution

The mammalian skull has been studied as several separate functional components for decades, but the study of modularity is a more recent, integrative approach toward quantitative examination of independent subsets of highly correlated traits, or modules. Although most studies of modularity focus on developmental and genetic systems, phenotypic modules have been noted in many diverse morphological structures. However, few studies have provided empirical data for comparing modules across higher taxonomic levels, limiting the ability to assess the broader evolutionary significance of modularity. This study uses 18-32 three-dimensional cranial landmarks to analyze phenotypic modularity in 106 mammalian species and demonstrates that cranial modularity is generally conserved in the evolution of therian mammals (marsupials and placentals) but differs between therians and monotremes, the two extant subclasses of Mammalia. Within therians, cluster analyses identify six distinct modules, but only three modules display significant integration in all species. Monotremes display only two highly integrated modules. Specific hypotheses of functional and developmental influences on cranial bones were tested. Theoretical correlation matrices for bones were constructed on the basis of shared function, tissue origin, or mode of ossification, and all three of these models are significantly correlated with observed correlation matrices for the mammalian cranium.     

Morphological integration and serial homology: A case study of the cranium and anterior vertebrae in salamanders

Serial homology or the repetition of equivalent developmental units and their derivatives is a phenomenon encountered in a variety of organisms, with the vertebrate axial skeleton as one of the most notable examples. Serially homologous structures can be viewed as an appropriate model system for studying morphological integration and modularity, due to the strong impact of development on their covariation. Here, we explored the pattern of morphological integration of the cranium and the first three serially homologous structures (atlas, first, and second trunk vertebrae) in salamandrid salamanders, using micro-CT scanning and three-dimensional geometric morphometrics. We explored the integration between structures at static and evolutionary levels. Effects of allometry on patterns of modularity were also taken into account. At the static level (within species), we analyzed inter-individual variation in shape to detect functional modules and intra-individual variation to detect developmental modules. Significant integration (based on inter-individual variation) among all structures was detected and allometry is shown to be an important integrating factor. The pattern of intra-individual, asymmetric variation indicates statistically significant developmental integration between the cranium and the atlas and between the first two trunk vertebrae. At the evolutionary level (among species), the cranium, atlas, and trunk vertebrae separate as different modules. Our results show that morphological integration at the evolutionary level coincides with morphological and functional differentiation of the axial skeleton, allowing the more or less independent evolutionary changes of the cranial skeleton and the vertebral column, regardless of the relatively strong integration at the static level. The observed patterns of morphological integration differ across levels, indicating different impacts of developmental and phylogenetic constraints and functional demands.     

Modularity and sense organs in the blind cavefish, Astyanax mexicanus

SUMMARY Mexican tetra (Astyanax mexicanus) exist as two morphs: a sighted (surface) form and a blind (cavefish) form. In the cavefish, some modules are lost, such as the eye and pigment modules, whereas others are expanded, such as the taste bud and cranial neuromast modules. We suggest that modularity can be viewed as being nested in a manner similar to Baupläne so that modules express unique sets of genes, cells, and processes. In terms of evolution, we conclude that natural selection can act on any of these hierarchical levels within modules or on all the sensory modules as a whole. We discuss interactions within and between modules with reference to the blind cavefish from both genetic and developmental perspectives. The cavefish represents an illuminating example of module interaction, uncoupling of modules, and module expansion.     

Modularity in the evolution of yeast protein interaction network

Protein interaction networks are known to exhibit remarkable structures: scale-free and small-world and modular structures. To explain the evolutionary processes of protein interaction networks possessing scale-free and small-world structures, preferential attachment and duplication-divergence models have been proposed as mathematical models. Protein interaction networks are also known to exhibit another remarkable structural characteristic, modular structure. How the protein interaction networks became to exhibit modularity in their evolution? Here, we propose a hypothesis of modularity in the evolution of yeast protein interaction network based on molecular evolutionary evidence. We assigned yeast proteins into six evolutionary ages by constructing a phylogenetic profile. We found that all the almost half of hub proteins are evolutionarily new. Examining the evolutionary processes of protein complexes, functional modules and topological modules, we also found that member proteins of these modules tend to appear in one or two evolutionary ages. Moreover, proteins in protein complexes and topological modules show significantly low evolutionary rates than those not in these modules. Our results suggest a hypothesis of modularity in the evolution of yeast protein interaction network as systems evolution.     

Modularity, comparative embryology and evo-devo: Developmental dissection of evolving body plans

Modules can be defined as quasi-autonomous units that are connected loosely with each other within a system. A need for the concept of modularity has emerged as we deal with evolving organisms in evolutionary developmental research, especially because it is unknown how genes are associated with anatomical patterns. One of the strategies to link genotypes with phenotypes could be to relate developmental modules with morphological ones. To do this, it is fundamental to grasp the context in which certain anatomical units and developmental processes are associated with each other specifically. By identifying morphological modularities as units recognized by some categories of general homology as established by comparative anatomy, it becomes possible to identify developmental modules whose genetic components exhibit coextensive expressions. This permits us to distinguish the evolutionary modification in which the identical morphological module simply alters its shape for adaptation, without being decoupled from the functioning gene network (‘coupled modularities’), from the evolution of novelty that involves a heterotopic shift between the anatomical and developmental modules. Using this formulation, it becomes possible, within the realm of Geoffroy's homologous networks, to reduce morphological homologies to developmental mechanistic terms by dissociating certain classes of modules that are often associated with actual shapes and functions.     

A MODULAR FRAMEWORK CHARACTERIZES MICRO‐ AND MACROEVOLUTION OF OLD WORLD MONKEY DENTITIONS

The study of modularity can provide a foundation for integrating development into studies of phenotypic evolution. The dentition is an ideal phenotype for this as it is developmentally relatively simple, adaptively highly significant, and evolutionarily tractable through the fossil record. Here, we use phenotypic variation in the dentition to test a hypothesis about genetic modularity. Quantitative genetic analysis of size variation in the baboon dentition indicates a genetic modular framework corresponding to tooth type categories. We analyzed covariation within the dentitions of six species of Old World monkeys (OWMs) to assess the macroevolutionary extent of this framework: first by estimating variance–covariance matrices of linear tooth size, and second by performing a geometric morphometric (GM) analysis of tooth row shape. For both size and shape, we observe across OWMs a framework of anterior and postcanine modules, as well as submodularity between the molars and premolars. Our results of modularity by tooth type suggest that adult variation in the OWM dentition is influenced by early developmental processes such as odontogenesis and jaw patterning. This study presents a comparison of genotypic modules to phenotypic modules, which can be used to better understand their action across evolutionary time scales.     

The road to modularity

A network of interactions is called modular if it is subdivided into relatively autonomous, internally highly connected components. Modularity has emerged as a rallying point for research in developmental and evolutionary biology (and specifically evo-devo), as well as in molecular systems biology. Here we review the evidence for modularity and models about its origin. Although there is an emerging agreement that organisms have a modular organization, the main open problem is the question of whether modules arise through the action of natural selection or because of biased mutational mechanisms.     

Evolutionary modularity of the mouse mandible: dissecting the effect of chromosomal reorganizations and isolation by distance in a Robertsonian system of Mus musculus domesticus

The mouse mandible consists of several morphogenetic units that are usually grouped into two main modules: the alveolar region and the ascending ramus. The genetic/ontogenetic modularity of the two regions implies that they might evolve independently to some extent. In particular, evolutionary modularity in quantitative traits could arise during chromosomal speciation due to lower gene flow in rearranged chromosomes. With the aim of uncovering the autonomous evolution of the mandible modules, the form variation of each of them was assessed in the house mouse Robertsonian system from Barcelona, in which chromosomal variation and geographical distance may act as isolation factors. The association between these factors and morphological changes was analysed to determine their contribution to the differentiation of each module. Although size changes in the two modules were highly correlated, shape changes were not, and their association with karyotype differences, but not geographical distance, was dependent on the module. The results support the existence of two evolutionary modules and highlight the importance of size in morphological integration of the mandible. They also suggest that geographical distance and chromosomal reorganizations reduce gene flow between karyotypically divergent populations, but although geographical distance represents a global barrier to gene flow, the isolation produced by a set of chromosomal reorganizations only affects particular modules, probably depending on the number and location of loci with effects on a particular morphological region.     

Drosophila wing modularity revisited through a quantitative genetic approach

To predict the response of complex morphological structures to selection it is necessary to know how the covariation among its different parts is organized. Two key features of covariation are modularity and integration. The Drosophila wing is currently considered a fully integrated structure. Here, we study the patterns of integration of the Drosophila wing and test the hypothesis of the wing being divided into two modules along the proximo‐distal axis, as suggested by developmental, biomechanical, and evolutionary evidence. To achieve these goals we perform a multilevel analysis of covariation combining the techniques of geometric morphometrics and quantitative genetics. Our results indicate that the Drosophila wing is indeed organized into two main modules, the wing base and the wing blade. The patterns of integration and modularity were highly concordant at the phenotypic, genetic, environmental, and developmental levels. Besides, we found that modularity at the developmental level was considerably higher than modularity at other levels, suggesting that in the Drosophila wing direct developmental interactions are major contributors to total phenotypic shape variation. We propose that the precise time at which covariance‐generating developmental processes occur and/or the magnitude of variation that they produce favor proximo‐distal, rather than anterior‐posterior, modularity in the Drosophila wing.     

Hormone signaling in evolution and development: a non-model system approach

Cooption and modularity are informative concepts in evolutionary developmental biology. Genes function within complex networks that act as modules in development. These modules can then be coopted in various functional and evolutionary contexts. Hormonal signaling, the main focus of this review, has a modular character. By regulating the activities of genes, proteins and other cellular molecules, a hormonal signal can have major effects on physiological and ontogenetic processes within and across tissues over a wide spatial and temporal scale. Because of this property, we argue that hormones are frequently involved in the coordination of life history transitions (LHTs) and their evolution (LHE). Finally, we promote the usefulness of a comparative, non-model system approach towards understanding how hormones function and guide development and evolution, highlighting thyroid hormone function in echinoids as an example.     

Modules, kinds, and homology

Developmental modules are best conceptualized as homeostatic property cluster natural kinds. As is true in other fields of biology, an individual may instantiate properties of various natural kinds. Through their dissociability, developmental modules can be recruited to function as evolutionary modules. The proper analogy to developmental modules, atoms, or biological species depends on the scope over which specific developmental modules allow generalizations. The nature of the relationship between developmental modules, evolutionary modules, and taxic (phylogenetic) homology are explored. Similarity of gene expression patterns and developmental pathways as captured by biological homology may support hypotheses of taxic homology, but not the other way around.     

Mosaic heterochrony and evolutionary modularity: the trilobite genus Zacanthopsis as a case study

Logical connections exist between evolutionary modularity and heterochrony, two unifying and structuring themes in the expanding field of evolutionary developmental biology. The former sees complex phenotypes as being made up of semi-independent units of evolutionary transformation; the latter requires such a modular organization of phenotypes to occur in a localized or mosaic fashion. This conceptual relationship is illustrated here by analyzing the evolutionary changes in the cranidial ontogeny of two related species of Cambrian trilobites. With arguments from comparative developmental genetics and functional morphology, we delineate putative evolutionary modules within the cranidium and examine patterns of evolutionary changes in ontogeny at both global and local scales. Results support a case of mosaic heterochrony, that is, a combination of local heterochronies affecting the different parts individuated in the cranidium, leading to the complex pattern of allometric repatterning observed at the global scale. Through this example, we show that recasting morphological analyses of complex phenotypes with a priori knowledge or hypotheses about their organizational and variational properties can significantly improve our interpretation and understanding of evolutionary changes among related taxa, fossil and extant. Such considerations open avenues to investigate the large-scale dynamics of modularity and its role in phenotypic evolution.     

The "eyespot module" and eyespots as modules: development, evolution, and integration of a complex phenotype

Organisms are inherently modular, yet modules also evolve in response to selection for functional integration or functional specialization of traits. For serially repeated homologous traits, there is a clear expectation that selection on the function of individual traits will reduce the integration between traits and subdivide a single ancestral module. The eyespots on butterfly wings are one example of serially repeated morphological traits that share a common developmental mechanism but are subject to natural and sexual selection for divergent functions. Here, I test two hypotheses about the organization of the eyespot pattern into independent dorsal-ventral and anterior-posterior modules, using a graphical modeling technique to examine patterns of eyespot covariation among and within wing surfaces in the butterfly Bicyclus anynana. Although there is a hierarchical and complex pattern of integration among eyespots, the results show a surprising mismatch between patterns of eyespot integration and the developmental and evolutionary eyespot units identified in previous empirical studies. These results are discussed in light of the relationships between developmental, functional, and evolutionary modules, and they suggest that developmental sources of independent trait variation are often masked by developmental sources of trait integration.