Integration and modularity of quantitative trait locus effects on geometric shape in the mouse mandible

The mouse mandible has long served as a model system for complex morphological structures. Here we use new methodology based on geometric morphometrics to test the hypothesis that the mandible consists of two main modules, the alveolar region and the ascending ramus, and that this modularity is reflected in the effects of quantitative trait loci (QTL). The shape of each mandible was analyzed by the positions of 16 morphological landmarks and these data were analyzed using Procrustes analysis. Interval mapping in the F(2) generation from intercrosses of the LG/J and SM/J strains revealed 33 QTL affecting mandible shape. The QTL effects corresponded to a variety of shape changes, but ordination or a parametric bootstrap test of clustering did not reveal any distinct groups of QTL that would affect primarily one module or the other. The correlations of landmark positions between the two modules tended to be lower than the correlations between arbitrary subsets of landmarks, indicating that the modules were relatively independent of each other and confirming the hypothesized location of the boundary between them. While these results are in agreement with the hypothesis of modularity, they also underscore that modularity is a question of the relative degrees to which QTL contribute to different traits, rather than a question of discrete sets of QTL contributing to discrete sets of traits.     

Chromosomal rearrangements,phenotypic variation and modularity: a case study from a contact zone between house mouse Robertsonian races in Central Italy

The Western European house mouse, Mus musculus domesticus, is well‐known for the high frequency of Robertsonian fusions that have rapidly produced more than 50 karyotipic races, making it an ideal model for studying the mechanisms of chromosomal speciation. The mouse mandible is one of the traits studied most intensively to investigate the effect of Robertsonian fusions on phenotypic variation within and between populations. This complex bone structure has also been widely used to study the level of integration between different morphogenetic units. Here, with the aim of testing the effect of different karyotypic assets on the morphology of the mouse mandible and on its level of modularity, we performed morphometric analyses of mice from a contact area between two highly metacentric races in Central Italy. We found no difference in size, while the mandible shape was found to be different between the two Robertsonian races, even after accounting for the genetic relationships among individuals and geographic proximity. Our results support the existence of two modules that indicate a certain degree of evolutionary independence, but no difference in the strength of modularity between chromosomal races. Moreover, the ascending ramus showed more pronounced interpopulation/race phenotypic differences than the alveolar region, an effect that could be associated to their different polygenic architecture. This study suggests that chromosomal rearrangements play a role in the house mouse phenotypic divergence, and that the two modules of the mouse mandible are differentially affected by environmental factors and genetic makeup.     

Does nasal echolocation influence the modularity of the mammal skull?

In vertebrates, changes in cranial modularity can evolve rapidly in response to selection. However, mammals have apparently maintained their pattern of cranial integration throughout their evolutionary history and across tremendous morphological and ecological diversity. Here, we use phylogenetic, geometric morphometric and comparative analyses to test the hypothesis that the modularity of the mammalian skull has been remodelled in rhinolophid bats due to the novel and critical function of the nasal cavity in echolocation. We predicted that nasal echolocation has resulted in the evolution of a third cranial module, the ‘nasal dome’, in addition to the braincase and rostrum modules, which are conserved across mammals. We also test for similarities in the evolution of skull shape in relation to habitat across rhinolophids. We find that, despite broad variation in the shape of the nasal dome, the integration of the rhinolophid skull is highly consistent with conserved patterns of modularity found in other mammals. Across their broad geographical distribution, cranial shape in rhinolophids follows two major divisions that could reflect adaptations to dietary and environmental differences in African versus South Asian distributions. Our results highlight the potential of a relatively simple modular template to generate broad morphological and functional variation 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.     

Specialization Can Drive the Evolution of Modularity

Organismal development and many cell biological processes are organized in a modular fashion, where regulatory molecules form groups with many interactions within a group and few interactions between groups. Thus, the activity of elements within a module depends little on elements outside of it. Modularity facilitates the production of heritable variation and of evolutionary innovations. There is no consensus on how modularity might evolve, especially for modules in development. We show that modularity can increase in gene regulatory networks as a byproduct of specialization in gene activity. Such specialization occurs after gene regulatory networks are selected to produce new gene activity patterns that appear in a specific body structure or under a specific environmental condition. Modules that arise after specialization in gene activity comprise genes that show concerted changes in gene activities. This and other observations suggest that modularity evolves because it decreases interference between different groups of genes. Our work can explain the appearance and maintenance of modularity through a mechanism that is not contingent on environmental change. We also show how modularity can facilitate co-option, the utilization of existing gene activity to build new gene activity patterns, a frequent feature of evolutionary innovations.     

Two‐module organization of the mandible in the yellow‐necked mouse: a comparison between two different morphometric approaches

Mandibles of yellow‐necked mouse (Apodemus flavicollis) were used to explore modularity. We tested a biological hypothesis that two separate modules (alveolar region and ascending ramus) can be recognized within the mandible. As a second research goal, we compared two different morphometric procedures under the assumption that methodological approaches that use either geometric or traditional morphometric techniques should give similar results. Besides confirmation of the predicted hypothesis of modularity, the application of both approaches revealed that: (i) modularity was somewhat more evident when it was analysed on the asymmetric (fluctuating asymmetry, FA) than on the symmetric (individual variation) component of variation; (ii) there is correspondence in the patterns of individual variation and FA, which indicates that integration of mandibular traits among individuals is primarily due to direct developmental interactions; and (iii) allometry does not obscure the hypothesized modularity for individual variation or for FA. In addition, traditional morphometric method allowed us to check whether allometry influenced each module to the same extent and to conclude that the ascending ramus is more heavily influenced by general size than the alveolar region. In studies of modularity, differences in methods can lead to discrepancies in the results, and therefore, some caution is required when comparing findings from different investigations. The substantial agreement between our results provides evidence that, when considering two‐module organization of the mouse mandible, direct comparison among studies that use the methods applied herein is, in great part, reliable.     

Morphological variation in house mice from the Robertsonian polymorphism area of Barcelona

Morphometric variation in the Robertsonian polymorphism zone of Barcelona of Mus musculus domesticus was studied by geometric morphometrics. This system is characterized by populations of reduced diploid number (2 n  = 27–39) surrounded by standard populations (2 n  = 40). We investigated the morphological variation in mice from this area, as well as the effect of geographical distance and karyotype on this variation. We also investigated the degree of co-variation between the two functional units of the mandible to explore the origin of this system (primary intergradation or secondary contact). The size and shape of the cranium, mandible and scapula were analysed for 226 specimens grouped by population, chromosome number and structural heterozygosity. Size was estimated as the centroid size, and shape was estimated after Procrustes superimposition. No significant differences in size between populations or chromosomal groups were detected. Diploid number, structural heterozygosity and local geographical isolation contributed to the differentiation in shape. Morphological differentiation between standard mice and Robertsonian specimens was observed, suggesting genetic isolation between these groups. Co-variation between the ascending ramus and alveolar region of the mandible was quantified by the trace correlation between landmark subsets of these modules. The trace values showed an ascending trend, correlated with the distance from the centre of the polymorphism area, a pattern consistent with a primary intergradation scenario.  © 2009 The Linnean Society of London, Biological Journal of the Linnean Society , 2009, 97 , 555–570.     

Evolution of median fin modules in the axial skeleton of fishes

Detailed examples of how hierarchical assemblages of modules change over time are few. We found broadly conserved phylogenetic patterns in the directions of development within the median fins of fishes. From these, we identify four modules involved in their positioning and patterning. The evolutionary sequence of their hierarchical assembly and secondary dissociation is described. The changes in these modules during the evolution of fishes appear to be produced through dissociation, duplication and divergence, and co-option. Although the relationship between identified median fin modules and underlying mechanisms is unclear, Hox addresses may be correlated. Comparing homologous gene expression and function in various fishes may test these predictions.The earliest actinopterygians likely had dorsal and anal fins that were symmetrically positioned via a positioning module. The common patterning (differentiation) of skeletal elements within the dorsal and anal fins may have been set into motion by linkage to this positioning module. Frequent evolutionary changes in dorsal and anal fin position indicate a high level of dissociability of the positioning module from the patterning module. In contrast, the patterning of the dorsal and anal fins remains linked: In nearly all fishes, the endo- and exoskeletal elements of the two fins co-differentiate. In all fishes, the exoskeletal fin rays differentiate in the same directions as the endoskeletal supports, indicating complete developmental integration. In acanthopterygians, a new first dorsal fin module evolved via duplication and divergence. The median fins provide an example of how basic modularity is maintained over 400 million years of evolution.     

Divergence with gene flow and fine-scale phylogeographical structure in the wedge-billed woodcreeper, Glyphorynchus spirurus, a Neotropical rainforest bird

Determining the relative roles of vicariance and selection in restricting gene flow between populations is of central importance to the evolutionary process of population divergence and speciation. Here we use molecular and morphological data to contrast the effect of isolation (by mountains and geographical distance) with that of ecological factors (altitudinal gradients) in promoting differentiation in the wedge-billed woodcreeper, Glyphorynchus spirurus , a tropical forest bird, in Ecuador. Tarsus length and beak size increased relative to body size with altitude on both sides of the Andes, and were correlated with the amount of moss on tree trunks, suggesting the role of selection in driving adaptive divergence. In contrast, molecular data revealed a considerable degree of admixture along these altitudinal gradients, suggesting that adaptive divergence in morphological traits has occurred in the presence of gene flow. As suggested by mitochondrial DNA sequence data, the Andes act as a barrier to gene flow between ancient subspecific lineages. Genome-wide amplified fragment length polymorphism markers reflected more recent patterns of gene flow and revealed fine-scale patterns of population differentiation that were not detectable with mitochondrial DNA, including the differentiation of isolated coastal populations west of the Andes. Our results support the predominant role of geographical isolation in driving genetic differentiation in G. spirurus , yet suggest the role of selection in driving parallel morphological divergence along ecological gradients.     

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.     

The Influence of Modularity on Cranial Morphological Disparity in Carnivora and Primates (Mammalia)

Background

Although variation provides the raw material for natural selection and evolution, few empirical data exist about the factors controlling morphological variation. Because developmental constraints on variation are expected to act by influencing trait correlations, studies of modularity offer promising approaches that quantify and summarize patterns of trait relationships. Modules, highly-correlated and semi-autonomous sets of traits, are observed at many levels of biological organization, from genes to colonies. The evolutionary significance of modularity is considerable, with potential effects including constraining the variation of individual traits, circumventing pleiotropy and canalization, and facilitating the transformation of functional structures. Despite these important consequences, there has been little empirical study of how modularity influences morphological evolution on a macroevolutionary scale. Here, we conduct the first morphometric analysis of modularity and disparity in two clades of placental mammals, Primates and Carnivora, and test if trait integration within modules constrains or facilitates morphological evolution.

Principal Findings

We used both randomization methods and direct comparisons of landmark variance to compare disparity in the six cranial modules identified in previous studies. The cranial base, a highly-integrated module, showed significantly low disparity in Primates and low landmark variance in both Primates and Carnivora. The vault, zygomatic-pterygoid and orbit modules, characterized by low trait integration, displayed significantly high disparity within Carnivora. 14 of 24 results from analyses of disparity show no significant relationship between module integration and morphological disparity. Of the ten significant or marginally significant results, eight support the hypothesis that integration within modules constrains morphological evolution in the placental skull. Only the molar module, a highly-integrated and functionally important module, showed significantly high disparity in Carnivora, in support of the facilitation hypothesis.

Conclusions

This analysis of within-module disparity suggested that strong integration of traits had little influence on morphological evolution over large time scales. However, where significant results were found, the primary effect of strong integration of traits was to constrain morphological variation. Thus, within Primates and Carnivora, there was some support for the hypothesis that integration of traits within cranial modules limits morphological evolution, presumably by limiting the variation of individual traits.     

Anatomical Network Analysis Shows Decoupling of Modular Lability and Complexity in the Evolution of the Primate Skull

Modularity and complexity go hand in hand in the evolution of the skull of primates. Because analyses of these two parameters often use different approaches, we do not know yet how modularity evolves within, or as a consequence of, an also-evolving complex organization. Here we use a novel network theory-based approach (Anatomical Network Analysis) to assess how the organization of skull bones constrains the co-evolution of modularity and complexity among primates. We used the pattern of bone contacts modeled as networks to identify connectivity modules and quantify morphological complexity. We analyzed whether modularity and complexity evolved coordinately in the skull of primates. Specifically, we tested Herbert Simon’s general theory of near-decomposability, which states that modularity promotes the evolution of complexity. We found that the skulls of extant primates divide into one conserved cranial module and up to three labile facial modules, whose composition varies among primates. Despite changes in modularity, statistical analyses reject a positive feedback between modularity and complexity. Our results suggest a decoupling of complexity and modularity that translates to varying levels of constraint on the morphological evolvability of the primate skull. This study has methodological and conceptual implications for grasping the constraints that underlie the developmental and functional integration of the skull of humans and other primates.     

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.     

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.     

Roles for modularity and constraint in the evolution of cranial diversity among Anolis lizards

Complex organismal structures are organized into modules, suites of traits that develop, function, and vary in a coordinated fashion. By limiting or directing covariation among component traits, modules are expected to represent evolutionary building blocks and to play an important role in morphological diversification. But how stable are patterns of modularity over macroevolutionary timescales? Comparative analyses are needed to address the macroevolutionary effect of modularity, but to date few have been conducted. We describe patterns of skull diversity and modularity in Caribbean Anolis lizards. We first diagnose the primary axes of variation in skull shape and then examine whether diversification of skull shape is concentrated to changes within modules or whether changes arose across the structure as a whole. We find no support for the hypothesis that cranial modules are conserved as species diversify in overall skull shape. Instead we find that anole skull shape and modularity patterns independently converge. In anoles, skull modularity is evolutionarily labile and may reflect the functional demands of unique skull shapes. Our results suggest that constraints have played little role in limiting or directing the diversification of head shape in Anolis lizards.     

Varieties of modules: kinds, levels, origins, and behaviors

This article began as a review of a conference, organized by Gerhard Schlosser, entitled "Modularity in Development and Evolution." The conference was held at, and sponsored by, the Hanse Wissenschaftskolleg in Delmenhorst, Germany in May, 2000. The article subsequently metamorphosed into a literature and concept review as well as an analysis of the differences in current perspectives on modularity. Consequently, I refer to general aspects of the conference but do not review particular presentations. I divide modules into three kinds: structural, developmental, and physiological. Every module fulfills none, one, or multiple functional roles. Two further orthogonal distinctions are important in this context: module-kinds versus module-variants-of-a-kind and reproducer versus nonreproducer modules. I review criteria for individuation of modules and mechanisms for the phylogenetic origin of modularity. I discuss conceptual and methodological differences between developmental and evolutionary biologists, in particular the difference between integration and competition perspectives on individualization and modular behavior. The variety in views regarding modularity presents challenges that require resolution in order to attain a comprehensive, rather than a piecemeal and fragmentary, evolutionary developmental biology. J. Exp. Zool. (Mol. Dev. Evol.) 291:116-129, 2001.     

Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions and Prdm9 allelic background

Despite the existence of formal models to explain how chromosomal rearrangements can be fixed in a population in the presence of gene flow, few empirical data are available regarding the mechanisms by which genome shuffling contributes to speciation, especially in mammals. In order to shed light on this intriguing evolutionary process, here we present a detailed empirical study that shows how Robertsonian (Rb) fusions alter the chromosomal distribution of recombination events during the formation of the germline in a Rb system of the western house mouse (Mus musculus domesticus). Our results indicate that both the total number of meiotic crossovers and the chromosomal distribution of recombination events are reduced in mice with Rb fusions and that this can be related to alterations in epigenetic signatures for heterochromatinization. Furthermore, we detected novel house mouse Prdm9 allelic variants in the Rb system. Remarkably, mean recombination rates were positively correlated with a decrease in the number of ZnF domains in the Prdm9 gene. The suggestion that recombination can be modulated by both chromosomal reorganizations and genetic determinants that control the formation of double-stranded breaks during meiosis opens new avenues for understanding the role of recombination in chromosomal speciation.