Evolutionary changes in the anatomy of the shoulder (shoulder blade and upper arm) are associated with some of the most important behavioral changes in modern humans and our hominin ancestors, such as reduced time spent in trees, increased tool use and manipulation, and incredibly accurate throwing. Considering much of evolution occurs via changes in how genes are turned on/off in the developing body, determining which genes and regulatory switches control shoulder development is of critical importance for understanding the genetic basis of skeletal shape and the sequence of events that has produced our unique shoulders. This project investigates the developmental and genetic mechanisms that control shoulder shape, by comparing shoulder shape in apes and humans, conducting experiments that will identify genes that are active during shoulder development, and analyzing these genetic data to reconstruct the unique evolution of the human shoulder. Broader impacts include training of underrepresented minority students, public science outreach through workshops and museum exhibits, and findings that may be informative for biomedical studies of shoulder dysfunction or disease.
The unique features of the human shoulder, consisting of the scapula and proximal humerus, evolved from an ancestral hominoid pattern, but recent fossils cast doubt as to the morphotype. In the human lineage, evolutionary shifts in shoulder morphology are associated with some of the most important behavioral changes in hominins, such as reduced arboreality, tool use and increased manipulation, and accurate throwing. The human shoulder is under strong developmental genetic programming in which key aspects of component positioning, orientation, and shape emerge in utero. This early shape morphogenesis is intriguing considering that the scapula arises from multiple cell populations, which condense and fuse to form integrated, yet morphologically distinct, bony elements, each of which is critical to adult function. Given this complexity, which developmental and genetic mechanisms control shoulder shape? Considering that much of phenotypic evolution occurs via changes in the non-coding regulatory genome, determining which genes and regulatory switches (e.g., enhancers) control shoulder morphogenesis is of critical importance for understanding the genetic basis of skeletal shape and for reconstructing the sequence of mutational events that has produced the unique human shoulder morphology. This proposal aims to illuminate developmental mechanisms contributing to the evolution of the human shoulder girdle using: 1) Geometric morphometrics including shape analyses and reconstructions of shoulder morphospaces in order to quantify and model evolutionary trajectories in shape variation in apes and humans; 2) RNA-seq and ChIP-seq experimental assays on embryonic mouse shoulder tissues to identify both genes and regulatory elements, respectively, that are differentially active in shoulder components; 3) comparative genomics on functionally identified sequences to identify base-pair differences between humans and chimps that contribute to shoulder variation; and 4) PAML likelihood ratio testing to identify phylogenetic timing of adaptive selection on functional coding and non-coding sequences and test alternative models of human shoulder evolution.
