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.

骨骼的形状和大小在整个动物体内和动物物种之间有所不同，但是尚不清楚导致不同骨头的潜在遗传机制。该博士学位论文项目将研究DNA“说明手册”，特别是在发育过程中开启或关闭基因表达的“开关”，这会导致人类和黑猩猩的髋部和肩部骨骼的形状差异。该项目将在现代人类骨骼进化的背景下提高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研究和培训； 1-2本科生还将有机会获得实验室经验。 Co-Pi将在哈佛大学的生命科学外展计划中使用她的工作，以便与新英格兰高中生物学教师和学生讨论这项研究以及其他人类进化和遗传学方面，理想地招募有兴趣的学生来参观实验室并担任夏季研究人员。 PI和Co-Pi与哈佛大学自然历史博物馆的紧密联系将允许开发展示骨骼生物学，遗传学和人类进化的公众展览和事件。研究人员讨论了许多进化压力，主要与双皮亚主义的采用有关，这些压力可能在pelvis和scapula nerforlogy of Hominin on homiminin volutive of pelvis和scapula soclogy of to hominin insimin insimins indovology of bipedalism中。然而，对于导致观察到的这些骨骼形状和结构变化的基本基因组机制知之甚少。该项目将研究基因组的一部分，这些部分先前被确定为在胚胎骨盆和肩cap骨发育过程中具有潜在的活性和调节功能。基因组序列被专门研究与DNA区域的重叠，这些区域表现出在人类谱系中被阳性选择的迹象。对于这些调节序列中的每一个，研究人员将测试序列控制基因活性的人类和黑猩猩版本，以及这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的序列，以产生现代人类骨盆和肩cap骨。该奖项反映了NSF的法定任务，并且使用基金会的知识分子优点和更广泛的影响审查标准，被认为值得通过评估来支持。