The developmental genetic basis for evolutionary variation in the hominin shoulder

肩部（肩胛骨和上臂）解剖结构的进化变化与现代人类和我们的古人类祖先的一些最重要的行为变化有关，例如减少在树上花费的时间，增加工具的使用和操作，以及令人难以置信的准确投掷。考虑到大部分进化是通过改变基因在发育中的身体中如何打开/关闭而发生的，确定哪些基因和调节开关控制肩膀发育对于理解骨骼形状的遗传基础和产生我们独特肩膀的事件序列至关重要。该项目研究控制肩膀形状的发育和遗传机制，通过比较猿和人类的肩膀形状，进行实验，以确定在肩膀发育过程中活跃的基因，并分析这些遗传数据，以重建人类肩膀的独特进化。更广泛的影响包括培训代表性不足的少数民族学生，通过研讨会和博物馆展览进行公共科学宣传，以及可能为肩部功能障碍或疾病的生物医学研究提供信息的发现。人类肩部的独特特征，由肩胛骨和近端肱骨组成，从祖先的类人猿模式进化而来，但最近的化石对形态型提出了质疑。在人类谱系中，肩部形态的进化变化与人类一些最重要的行为变化有关，例如减少树栖性，工具使用和增加操纵，以及准确投掷。人类的肩膀是在强大的发育遗传编程，其中组件的定位，方向和形状的关键方面出现在子宫内。考虑到肩胛骨是由多个细胞群形成的，这些细胞群凝聚并融合形成完整的、但在形态上不同的骨元素，其中每一个对成年功能都至关重要，这种早期的形状形态发生是有趣的。考虑到这种复杂性，哪些发育和遗传机制控制着肩部形状？考虑到许多表型进化是通过非编码调控基因组的变化发生的，确定哪些基因和调控开关（例如，增强子）控制肩部形态发生对于理解骨骼形状的遗传基础和重建产生独特的人类肩部形态的突变事件的序列是至关重要的。本研究旨在阐明人类肩胛带的发育机制，包括：1）几何形态测量学，包括肩部形态空间的形状分析和重建，以量化和模拟猿和人类形状变化的进化轨迹; 2）对胚胎小鼠肩组织的RNA-seq和ChIP-seq实验测定，以分别鉴定基因和调控元件，3）功能鉴定序列的比较基因组学，以确定人类和黑猩猩之间的碱基对差异，有助于肩膀的变化;和4）PAML似然比测试，以确定适应性选择功能编码和非编码序列的系统发育时间和测试人类肩膀进化的替代模型。

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.