Selection for increased tibia length in mice alters skull shape through parallel changes in developmental mechanisms

Abstract

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.

MusMorph, a database of standardized mouse morphology data for morphometric meta-analyses

“…Furthermore, while most wildtype specimens fall within the control experimental group, there are cases where they can exhibit mutant-like phenotypes and be categorized as such. One example in MusMorph is the artificial selection Longshanks dataset 74 , which through many generations of artificial selection produced wildtype specimens with extreme tibia and craniofacial phenotypes 75 , 76 .…”

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

“…While there is mutual evolutionary constraint among the limb girdles and basicranium, it is unknown how these may relate to traits of the upper or lower limbs. While various studies have investigated the covariance and/or evolutionary relationships within different parts of the human skeleton (i.e., among traits of the skull, or among the limb elements), no study to date has evaluated whether the human cranium and limb segments have potential evolutionary covariance, though experimental research on the Longshanks mice indicates there may be parallel evolutionary connections between these skeletal regions (Unger et al, 2021). Among the limb elements, lower covariation has been reported between the upper and lower limb in humans compared to other primates (Young et al, 2010)-humans have more potential evolutionary independence among the limbs than other apes, and all apes are less integrated than monkeys-and potential correlated responses to selection have been reported between the tibia, radius, and humerus (Savell et al, 2016) in humans.…”

“…We also advocate for researchers to take a "whole-organism" view of research, recognizing that there is non-obvious genetic covariance among various aspects of an organism's morphology (e.g., the basicranium and limb girdles in primates as revealed by Agosto and Auerbach (2021), or the leg and the cranium in mice as discovered by Unger et al (2021)) in addition to more predictable covariance. Such covariance has important consequences on morphological evolution: as we discuss in more detail below, only with genetic variance can any given trait respond to selection, but not all the variance in a trait is available to respond.…”

“…Thus, quantitative genetics allows for the creation of a more nuanced and robust picture of trait evolution. In addition, this approach highlights regions or subsets of traits that may deserve further evaluation using a combined evolutionary and developmental ("evo-devo") framework, potentially allowing us to narrow down specific mechanisms driving observed change (e.g., Unger et al, 2021;Young et al, 2019Young et al, , 2022.…”

Recentering forensic anthropology within a multifaceted body of evolutionary theory: Strengthening method by making theory explicit

“…Rather, because of pleiotropy and linkage disequilibrium (Cheverud, 1996), the developmental system has a propensity to produce variation and covariation among functionally related traits, thus generating patterns of morphological integration (Hallgrímsson et al, 2006;Hallgrímsson et al, 2009). Examples of such integration (often manifested as covariation between seemingly unrelated traits) and the resulting implications for multitrait evolution have been found and discussed at length in humans (e.g., Fischer & Mitteroecker, 2015;Grabowski et al, 2011;Savell et al, 2016), nonhuman primates (e.g., Agosto & Auerbach, 2021;Kawada et al, 2020;Rolian, 2009), and model animals (e.g., Hallgrímsson et al, 2006;Unger, Devine, Hallgrímsson, & Rolian, 2021). As such, some traits analyzed by forensic anthropologists may not be under active selection but arise as necessary byproducts of other traits-(originally termed spandrels by Gould & Lewontin, 1979).…”