Bones in the vertebrate cranial base and limb skeleton grow by endochondral ossification, under the control of growth plates. Mechanisms of endochondral ossification are conserved across growth ...plates, which increases covariation in size and shape among bones, and in turn may lead to correlated changes in skeletal traits not under direct selection. We used micro-CT and geometric morphometrics to characterize shape changes in the cranium of the Longshanks mouse, which was selectively bred for longer tibiae. We show that Longshanks skulls became longer, flatter, and narrower in a stepwise process. Moreover, we show that these morphological changes likely resulted from developmental changes in the growth plates of the Longshanks cranial base, mirroring changes observed in its tibia. Thus, indirect and non-adaptive morphological changes can occur due to developmental overlap among distant skeletal elements, with important implications for interpreting the evolutionary history of vertebrate skeletal form.
The shape of the human face and skull is largely genetically determined. However, the genomic basis of craniofacial morphology is incompletely understood and hypothesized to involve protein-coding ...genes, as well as gene regulatory sequences. We used a combination of epigenomic profiling, in vivo characterization of candidate enhancer sequences in transgenic mice, and targeted deletion experiments to examine the role of distant-acting enhancers in craniofacial development. We identified complex regulatory landscapes consisting of enhancers that drive spatially complex developmental expression patterns. Analysis of mouse lines in which individual craniofacial enhancers had been deleted revealed significant alterations of craniofacial shape, demonstrating the functional importance of enhancers in defining face and skull morphology. These results demonstrate that enhancers are involved in craniofacial development and suggest that enhancer sequence variation contributes to the diversity of human facial morphology.
Development and the evolvability of human limbs Young, Nathan M; Wagner, Günter P; Hallgrímsson, Benedikt
Proceedings of the National Academy of Sciences - PNAS,
02/2010, Letnik:
107, Številka:
8
Journal Article
Recenzirano
Odprti dostop
The long legs and short arms of humans are distinctive for a primate, the result of selection acting in opposite directions on each limb at different points in our evolutionary history. This mosaic ...pattern challenges our understanding of the relationship of development and evolvability because limbs are serially homologous and genetic correlations should act as a significant constraint on their independent evolution. Here we test a developmental model of limb covariation in anthropoid primates and demonstrate that both humans and apes exhibit significantly reduced integration between limbs when compared to quadrupedal monkeys. This result indicates that fossil hominins likely escaped constraints on independent limb variation via reductions to genetic pleiotropy in an ape-like last common ancestor (LCA). This critical change in integration among hominoids, which is reflected in macroevolutionary differences in the disparity between limb lengths, facilitated selection for modern human limb proportions and demonstrates how development helps shape evolutionary change.
Robustness to perturbation is a fundamental feature of complex organisms. Mutations are the raw material for evolution, yet robustness to their effects is required for species survival. The ...mechanisms that produce robustness are poorly understood. Nonlinearities are a ubiquitous feature of development that may link variation in development to phenotypic robustness. Here, we manipulate the gene dosage of a signaling molecule, Fgf8, a critical regulator of vertebrate development. We demonstrate that variation in Fgf8 expression has a nonlinear relationship to phenotypic variation, predicting levels of robustness among genotypes. Differences in robustness are not due to gene expression variance or dysregulation, but emerge from the nonlinearity of the genotype-phenotype curve. In this instance, embedded features of development explain robustness differences. How such features vary in natural populations and relate to genetic variation are key questions for unraveling the origin and evolvability of this feature of organismal development.
A central issue in biology concerns the presence, timing and nature of phylotypic periods of development, but whether, when and why species exhibit conserved morphologies remains unresolved. Here, we ...construct a developmental morphospace to show that amniote faces share a period of reduced shape variance and convergent growth trajectories from prominence formation through fusion, after which phenotypic diversity sharply increases. We predict in silico the phenotypic outcomes of unoccupied morphospaces and experimentally validate in vivo that observed convergence is not due to developmental limits on variation but instead from selection against novel trajectories that result in maladaptive facial clefts. These results illustrate how epigenetic factors such as organismal geometry and shape impact facial morphogenesis and alter the locus of adaptive selection to variation in later developmental events.
Characterising phenotypes often requires quantification of anatomical shape. Quantitative shape comparison (morphometrics) traditionally uses manually located landmarks and is limited by landmark ...number and operator accuracy. Here, we apply a landmark-free method to characterise the craniofacial skeletal phenotype of the Dp1Tyb mouse model of Down syndrome and a population of the Diversity Outbred (DO) mouse model, comparing it with a landmark-based approach. We identified cranial dysmorphologies in Dp1Tyb mice, especially smaller size and brachycephaly (front-back shortening), homologous to the human phenotype. Shape variation in the DO mice was partly attributable to allometry (size-dependent shape variation) and sexual dimorphism. The landmark-free method performed as well as, or better than, the landmark-based method but was less labour-intensive, required less user training and, uniquely, enabled fine mapping of local differences as planar expansion or shrinkage. Its higher resolution pinpointed reductions in interior mid-snout structures and occipital bones in both the models that were not otherwise apparent. We propose that this landmark-free pipeline could make morphometrics widely accessible beyond its traditional niches in zoology and palaeontology, especially in characterising developmental mutant phenotypes.
SUMMARY
Research conducted under the label of evolutionary developmental biology has tended to revolve around a few central issues such as modularity, integration, and canalization. Yet, as the field ...has grown, it has become increasingly difficult to define in terms of its central question and relation to broader evolutionary concerns. We argue that these central issues of evo‐devo gain their currency from connections to a central question that defines the field, and we propose that this central question is about the nature of evolvability. However, not all research currently carried out under the label of “evo‐devo” speaks to this focal concern. The aim of this article is therefore to argue for a precise formulation of evolutionary developmental biology's core question.
Fitness-related traits tend to have low heritabilities. Conversely, morphology tends to be highly heritable. Yet, many fitness-related performance traits such as running speed or bite force depend ...critically on morphology. Craniofacial morphology correlates with bite performance in several groups including rodents. However, within species, this relationship is less clear, and the genetics of performance, morphology and function are rarely analyzed in combination. Here, we use a half-sib design in outbred wild-derived
Mus musculus
to study the morphology-bite force relationship and determine whether there is additive genetic (co-)variance for these traits. Results suggest that bite force has undetectable additive genetic variance and heritability in this sample, while morphological traits related mechanically to bite force exhibit varying levels of heritability. The most heritable traits include the length of the mandible which relates to bite force. Despite its correlation with morphology, realized bite force was not heritable, which suggests it is less responsive to selection in comparison to its morphological determinants. We explain this paradox with a non-additive, many-to-one mapping hypothesis of heritable change in complex traits. We furthermore propose that performance traits could evolve if pleiotropic relationships among the determining traits are modified.
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.
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.
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