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

博士论文研究：探索人类基因组塑造骨盆和肩胛骨进化的积极选择区域

• 批准号: 1847979
• 负责人: Terence Capellini
• 金额: $ 3.38万
• 依托单位: Harvard University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1847979&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Exploration; Positively

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.

动物体内和动物物种之间的骨骼形状和大小各不相同，但导致骨骼外观不同的潜在遗传机制尚不清楚。这个博士论文项目将研究DNA“指导手册”，特别是在发育过程中打开或关闭基因表达的“开关”，从而导致人类和黑猩猩的髋骨和肩骨的形状差异。该项目将在现代人类骨骼进化的背景下推进有关髋部和肩部发育遗传学的知识。该项目将支持研究生研究和培训； 1-2名本科生还将有机会获得实验室经验。联合首席研究员将利用她在哈佛大学生命科学外展项目中的工作机会，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，最好招募感兴趣的学生参观实验室并担任暑期研究人员。首席研究员和副首席研究员与哈佛自然历史博物馆的密切联系将有助于开展展示骨骼生物学、遗传学和人类进化的公共展览和活动。研究人员讨论了许多进化压力，主要与两足行走有关，这些压力可能在古人类进化过程中对骨盆和肩胛骨的形态产生了影响。然而，人们对导致这些骨骼形状和结构发生变化的潜在基因组机制知之甚少。该项目将研究先前被鉴定为在胚胎骨盆和肩胛骨发育过程中具有潜在活性和调节功能的基因组部分。正在专门研究的基因组序列与 DNA 区域重叠，这些区域显示出在人类谱系中受到正向选择的迹象。对于每一个调控序列，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。这项工作将有助于识别在人类进化过程中可能被选择的序列，以产生现代人类骨盆和肩胛骨。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。