Doctoral Dissertation Research: Exploration of Positively Selected Regions of the Human Genome Shaping Pelvis and Scapula Evolution

骨骼的形状和大小在整个动物身体和动物物种之间都有所不同，但导致骨骼外观不同的潜在遗传机制还没有得到很好的理解。这个博士论文项目将研究DNA“指令手册”，特别是在发育过程中打开或关闭基因表达的“开关”，这导致人类和黑猩猩的髋骨和肩胛骨的形状差异。该项目将在现代人类骨骼进化的背景下推进有关髋关节和肩部发育遗传学的知识。该项目将支持研究生的研究和培训; 1-2名本科生也将有机会获得实验室经验。共同PI将利用她在哈佛大学生命科学外展计划中的工作，与新英格兰高中生物教师和学生讨论这项研究以及人类进化和遗传学的其他方面，理想情况下招募感兴趣的学生参观实验室并担任暑期研究人员。PI和co-PI与哈佛自然历史博物馆的密切联系将允许开发公共展览和活动，展示骨骼生物学，遗传学和人类进化。研究人员已经讨论了一些进化压力，主要与采用两足动物有关，这些压力可能在古人类进化过程中对骨盆和肩胛骨形态起作用。然而，人们对导致这些骨骼形状和结构变化的潜在基因组机制知之甚少。该项目将研究先前被确定为在胚胎骨盆和肩胛骨发育期间具有潜在活性和调节功能的基因组部分。被专门研究的基因组序列与显示出在人类谱系中受到正选择的迹象的DNA区域重叠。对于这些调控序列中的每一个，研究人员将测试人类和黑猩猩版本的序列是否控制基因活性，以及两个物种之间的基因活性是否存在差异。这项工作将有助于确定在人类进化过程中可能被选择产生现代人类骨盆和肩胛骨的序列。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

Bones differ in shape and size throughout an animal's body and between animal species, but the underlying genetic mechanisms that result in different looking bones are not well understood. This doctoral dissertation project will investigate DNA "instruction manuals," particularly the "switches" that turn gene expression on or off during development, that result in shape differences in hip and shoulder bones of humans and chimpanzees. The project will advance knowledge about hip and shoulder developmental genetics in the context of modern human skeletal evolution. The project will support graduate research and training; 1-2 undergraduates also will have the opportunity to gain lab experience. The co-PI will use her work in a Life Science Outreach program at Harvard University as an opportunity to discuss this research and other facets of human evolution and genetics with New England high school biology teachers and students, ideally recruiting interested students to visit the lab and serve as summer researchers. The PI and co-PI's close ties with the Harvard Museum of Natural History will allow for the development of public exhibits and events that showcase bone biology, genetics, and human evolution.Researchers have discussed a number of evolutionary pressures, primarily related to the adoption of bipedalism, that are likely to have acted on pelvis and scapula morphology during hominin evolution. However, little is known about underlying genomic mechanisms that resulted in the observed changes in the shape and structure of these bones. This project will investigate portions of the genome that were previously identified as having potential activity and regulatory functions during embryonic pelvis and scapula development. The genomic sequences being specifically investigated overlap with regions of DNA that show signs of having been under positive selection in the human lineage. For each of these regulatory sequences, the researchers will test whether the human and chimpanzee versions of the sequence control gene activity, and whether there are differences in gene activity between the two species. This work will help to identify sequences likely to have been under selection during human evolution to produce the modern human pelvis and scapula.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.