Correlated Evolution of the Skeletal System in Mice Selectively Bred for Longer Tibiae
Creators: name: Unger, Colton Michael
Publisher: name: Science
Year: 2024
Subjects: subject: Evolutionary Developmental Biology
subject: Limb Development
subject: Skeletal Development
subject: Correlated Evolution
subject: Artificial Selection
subject: Education--Sciences
subject: Anatomy
subject: Genetics
subject: FOS: Biological sciences
subject: Biology--Cell
subject: Biology--Molecular

description: Organisms are complex systems of traits, which grow together and influence each other during development, leading to covariation among anatomical structures. Underlying genetic and developmental correlations between traits can influence evolutionary trajectories, and may lead to indirect, non-adaptive, or mal-adaptive responses to selection in a process called correlated evolution. Thus, distinct traits that are developmentally or functionally related are unlikely to evolve independently, and selection can result in off-target phenotypic change. Skeletal tissues tend to covary significantly in length and shape due to their shared functional role (e.g., locomotion) and shared mechanism of development, known as endochondral ossification (EO). Together, these features of mammalian skeletal tissues lead to strong covariation between skeletal elements, such as limb bones, vertebrae, and to a lesser extent, the cranial bones. The mechanism of EO in bone development is also reinitiated during the repair of long bone fractures. Therefore, there is great potential for correlated responses to selection in skeletal traits, potentially leading to correlated phenotypic changes when a given skeletal trait is under direct selection. To study correlated evolution in skeletal traits, I used the Longshanks mouse, which was selectively bred for increases in adult tibia length independent of body mass, resulting in 15-20% longer tibiae than Controls due to increased rates of EO during development. Using bone imaging, geometric morphometrics, histomorphometry, and transcriptomics, I characterized potential correlated changes to other traits in Longshanks that utilize the program of EO, including other off-target long bones, the cranium, and the repair of bone fractures. Using this multifaceted approach, I demonstrated that the cranium and postcranial skeleton of Longshanks have differentially elongated during the selection process, which coincided with changes to gene expression and chondrocyte behavior that resembled documented trends in the tibia. In doing so, I identified molecular and cellular signatures underlying skeletal trait correlations and identified pathways contributing to the local and global scaling of skeletal traits. Moreover, I demonstrated that Longshanks repairs unstabilized tibia fractures faster than Controls without compromising bone quality, owing to an accelerated EO phase of repair at the genetic and tissue levels. Together, this work provides strong empirical evidence of correlated trait evolution and furthers our understanding of how covariation shapes evolutionary trajectories at the microevolutionary scale, with implications for understanding morphological divergence in skeletal form and function.