Correlated Changes in the Postcranial Skeleton of Mice Selectively Bred for Longer Tibiae

In this study, we used a large, multi-generational sample of mice from the Longshanks experiment to quantify potential correlated phenotypic changes in the limbs, girdles, and vertebral column of the Longshanks skeleton over time. We show that selection for increased tibia length caused a systemic increase in the size of skeletal elements in Longshanks post-cranium throughout time, with a disproportionately large response in the tibia and pelvis. Selection for skeletal length independent of body mass resulted in allometrically larger postcranial skeletons in Longshanks. The magnitudes of correlated response throughout the Longshanks postcranium tended to reflect known evolutionary, developmental, and spatial relationships, providing empirical evidence for the influence of integration on shaping skeletal selection responses. Furthermore, we demonstrate that these patterns are established in the early developing post-cranial skeleton in neonatal Longshanks, and may be, in part, due to heterochrony in the establishment of the secondary ossification center (SOC). Lastly, using a Next Generation Sequencing (NGS) approach, we identify both bone specific sets of differentially expressed (DE) genes (local factors), and core suites of EO related genes that are differentially expressed across many developing growth plates (systemic factors) in Longshanks compared to Controls. Interestingly, there was little overlap of DE genes between each Longshanks line, suggesting different pathways to the same evolutionary outcome.