Biology subjects

Roseman, C. C.

Publications and source records attributed to Roseman, C. C..

4 recordsLinked to original sources

bioRxiv2025

The inhibitory cascade model and evolution in segmentally organized tissues

The inhibitory cascade model (ICM) of morphogenesis is an effort to link development to the production of variation, which can influence evolutionary trajectories. The ICM proposes that serially developing features, such as molar teeth, is governed by the relative magnitudes of one activating and one inhibiting developmental process. The statistical expectations of the ICM are typically expressed and analyzed on a first-element standardized scale and seem to be a good predictor of molar proportions. However, the ICM has been applied to traits that occur in series but do not develop in sequence and still recovers as good a fit as when applied to serially developing traits. Such an undiscriminating result raises questions about whether the fit of the ICM is an artifact of standardization. The mathematical rendition of the ICM do not correspond with the verbal descriptions of the developmental argument. Applying our novel re-articluation of the ICM to biological, non-biological, and simulated data, we demonstrate that the apparent goodness of fit of the ICM to many biological systems is an artifact of scaling correlated values with a common denominator. There is little evidence supporting the ICM at the developmental, variational, or evolutionary levels.

evolutionary biology↗

bioRxiv2023

Between-group heritability and the status of hereditarianism as an evolutionary science

Hereditarianism is a school of thought that contends there are substantial evolved cognitive and behavioral differences among groups of humans which are both resistant to environmental intervention and are a root cause of differential social outcomes across groups. The relationship of betweengroup heritability [Formula] to within-group heritability [Formula] is one of the key theoretical components of hereditarianism and forms one of the bases for its claim to be an evolutionary science. Here, we examine the relationship between [Formula]and [Formula] and its application to problems in the hereditarian literature from an evolutionary genetic perspective. We demonstrate that the formulation of the relationship between [Formula] and [Formula]used in the hereditarian literature has no evolutionary content. By re-writing the relationship between [Formula] and[Formula] in a novel evolutionary framework, we demonstrate that there is no way to predict[Formula] using[Formula] without considerable additional theory that is absent from the hereditarian literature. Furthermore, we demonstrate that the hereditarian technique that uses[Formula] and [Formula] as a means of judging whether a given difference between groups may be plausibly ameliorated through environmental intervention is mathematically flawed. Lastly, we fill a gap in the hereditarian literature by writing out a means of using [Formula] to predict the absolute difference between groups under a neutral evolutionary model and find that it is much smaller than claimed by hereditarians. In conclusion, we propose a path forward for the study of human variation that moves us past the ill-conceived nature vs. nurture question and allows us to focus on more productive issues.

genetics↗

bioRxiv2020

Shapes and Genescapes: Mapping Multivariate Phenotype-Biological Process Associations for Craniofacial Shape

Realistic mappings of genes to morphology are inherently multivariate on both sides of the equation. The importance of coordinated gene effects on morphological phenotypes is clear from the intertwining of gene actions in signaling pathways, gene regulatory networks, and developmental processes underlying the development of shape and size. Yet, current approaches tend to focus on identifying and localizing the effects of individual genes and rarely leverage the information content of high dimensional phenotypes. Here, we explicitly model the joint effects of biologically coherent collections of genes on a multivariate trait--craniofacial shape -- in a sample of n = 1,145 mice from the Diversity Outbred (DO) experimental line. We use biological process gene ontology (GO) annotations to select skeletal and facial development gene sets and solve for the axis of shape variation that maximally covaries with gene set marker variation. We use our process-centered, multivariate genotype-phenotype (MGP) approach to determine the overall contributions to craniofacial variation of genes involved in relevant processes and how variation in different processes corresponds to multivariate axes of shape variation. Further, we compare the directions of effect in phenotype space of mutations to the primary axis of shape variation associated with broader pathways within which they are thought to function. Finally, we leverage the relationship between mutational and pathway-level effects to predict phenotypic effects beyond craniofacial shape in specific mutants. We also introduce an online application which provides users the means to customize their own process-centered craniofacial shape analyses in the DO. The process-centered approach is generally applicable to any continuously varying phenotype and thus has wide-reaching implications for complex-trait genetics.

genomics↗

bioRxiv2019

Facial shape and allometry quantitative trait locus intervals in the Diversity Outbred mouse are enriched for known skeletal and facial development genes

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 QTLs 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.\n\nAuthor SummaryThe 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.

genetics↗