Variation in mouse pelvic morphology maps to locations enriched in Sox9 Class II and Pitx1 regulatory features

Abstract

Variation in pelvic morphology has a complex genetic basis and its patterning and specification is governed by conserved developmental pathways. Whether the mechanisms underlying the differentiation and specification of the pelvis also produce the morphological covariation on which natural selection may act, is still an open question in evolutionary developmental biology. We use high‐resolution quantitative trait locus (QTL) mapping in the F34 generation of an advanced intercross experiment (LG,SM‐G34) to characterize the genetic architecture of the mouse pelvis. We test the prediction that genomic features linked to developmental patterning and differentiation of the hind limb and pelvis and the regulation of chondrogenesis are overrepresented in QTL. We find 31 single QTL trait associations at the genome‐ or chromosome‐wise significance level coalescing to 27 pleiotropic loci. We recover further QTL at a more relaxed significance threshold replicating locations found in a previous experiment in an earlier generation of the same population. QTL were more likely than chance to harbor Pitx1 and Sox9 Class II chromatin immunoprecipitation‐seq features active during development of skeletal features. There was weak or no support for the enrichment of seven more categories of developmental features drawn from the literature. Our results suggest that genotypic variation is channeled through a subset of developmental processes involved in the generation of phenotypic variation in the pelvis. This finding indicates that the evolvability of complex traits may be subject to biases not evident from patterns of covariance among morphological features or developmental patterning when either is considered in isolation.

Morphology, evolution, and the whole organism imperative: Why evolutionary questions need multi‐trait evolutionary quantitative genetics

“…As most of the data types and questions asked by biological anthropologists are inherently retrospective, the kinds of data and repeatability afforded by experimental methods are not available for the types of questions that anthropologists ask. Nonetheless, biological anthropologists would benefit by familiarizing themselves with the application of evolvability and morphological integration estimation to experimental model organisms (from plant to murine models), as it is in experimental studies that researchers have determined the limitations of integration (e.g., Roseman et al, 2020), measured how genotypes map to phenotypes (e.g., Lucas et al, 2018), and quantified the developmental complexity of complex traits (e.g., Green et al, 2017Green et al, , 2019, refining how researchers may interpret the results of quantitative trait evolutionary modeling.…”

“…Estimates of evolvability and integration only provide a framework for the evolutionary potential of traits, but are unable to assess through what processes traits ultimately did evolve and the effect this had on morphological variation. To assess the actual evolutionary processes that led to trait variation, researchers need to use either experimental biology (e.g., Garland & Rose, 2009; Marchini & Rolian, 2018; Roseman et al, 2020; Young et al, 2022) or the comparative method (e.g., Felsenstein, 1985; Harvey & Pagel, 1991; Leroi et al, 1994; Martins, 2000; Martins & Hansen, 1997).…”

“…In effect, we encourage anthropologists to re‐integrate their study of morphology across the organism (not necessarily limited to the skeleton, though we focus on the skeleton herein). Even Washburn noted in 1951 that “[t]he anatomy of life, of integrated function, does not know the artificial boundaries which still govern the dissection of a corpse.” Echoing his call for change in how anthropologists interrogate primate evolution, researchers should leverage information made available through quantitative genetic methods and develop hypotheses that assess the evolution of morphological traits across the body, as informed by genetic and developmental information (see, e.g., Matsuoka et al, 2005; Roseman et al, 2020; Unger et al, 2021; Young et al, 2019).…”

Sex estimation from morphology in living animals and dinosaurs

“…The remaining species were then tested for sexual dimorphisms using Multivariate Analysis of Variance (MANOVA) based on all morphological measurements, and species with at least weakly significant differences between the sexes (p < 0.1) were retained. This left 139 species in the data (Table 1), containing 53 arthropods (38 arachnids (Buzatto et al, 2014), 4 crustacean (Fernandes Martins et al, 2017;Sørdalen et al, 2020), 7 insects (Punzalan & Rowe, 2015)), 1 cnidarian (González-Espinosa et al, 2018), and 89 vertebrates (1 amphibian (De Lisle, Paiva, & Rowe, 2018), 2 birds (Hsu et al, 2014;Poissant et al, 2016), 6 mammals (Christiansen & Harris, 2012;Roseman et al, 2020), 8 osteichthyes (Ronco, Roesti, & Salzburger, 2019;Garcia & Zuanon, 2019), and 72 reptiles (Sanger et al, 2013;Massetti et al, 2017;Burbrink, 2019)).…”