The origins and evolution of ancient genomic structural variants in hominins

古人类古代基因组结构变异的起源和进化

• 批准号: 2123284
• 负责人: Omer Gokcumen
• 金额: $ 30.62万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2123284&HistoricalAwards=false
• 关键词: origins; evolution; ancient; genomic; structural

This study explores hominin genetic variation, specifically focusing on previously understudied structural variants such as deletions and duplications of large DNA segments. The research advances knowledge about hominin adaptations and evolution from the distant past into the present, with anticipated outcomes emphasizing the shared genetic legacy of all humanity going back hundreds of thousands of years. The project supports the study of structural variants and anthropological genomics through training, methods development, and collaboration. Through planned workshops, scholars in the field can discuss the challenges and opportunities for swiftly and effectively disseminating diverse anthropological datasets and computational approaches. The project also serves as a framework to continue the training of a diverse undergraduate and graduate trainee community, as well as engage with the public to promote STEM training and anthropological genomics, especially through collaborations with the Genome, Environment, and Microbiome Center of Excellence at the University at Buffalo. Genomic structural variants, which are deletions, duplications, inversions, and translocations of large genetic segments in mammalian genomes, have not been a major focus in anthropological genetics because of methodological challenges and the cost of studying these types of variants. However, as new technologies make studying these variants more feasible, new research suggests a broad and previously underappreciated effect of structural variants on human evolution. The study addresses hypotheses about balancing and positive selection as processes maintaining structural variants in the human lineage and generates opportunities for follow-up research to investigate the functional impact of structural variants, some of which may have biomedical relevance. The study has the potential to be transformative in our understanding of recent human evolution and the role of specific structural variants in shaping human biological variation.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.

这项研究探讨了人类遗传变异，专门针对先前研究的结构变异，例如大型DNA片段的缺失和重复。该研究促进了有关人类适应和从遥远的过去发展到现在的知识，预期的结果强调了所有人类的共同遗传遗产，可以追溯到数十万年前。该项目通过培训，方法开发和协作来支持对结构变异和人类学基因组学的研究。通过计划的研讨会，该领域的学者可以讨论迅速有效地传播各种人类学数据集和计算方法的挑战和机会。该项目还可以作为一个框架，以继续培训多样化的本科和研究生实习生社区，并与公众互动，以促进STEM培训和人类学基因组学，尤其是通过与基因组，环境和微生物组卓越中心的合作。基因组结构变异是哺乳动物基因组中大遗传段的缺失，重复，反转和易位，由于方法论挑战和研究这些类型的变异的成本，因此并不是人类学遗传学的主要重点。但是，随着新技术使研究这些变体变得更加可行，新的研究表明，结构变体对人类进化的广泛且以前不足的影响。该研究介绍了关于维持人类谱系结构变异的过程的平衡和积极选择的假设，并为后续研究创造了机会，以研究结构变异的功能影响，其中一些可能具有生物医学相关性。这项研究有可能在我们对最近的人类进化的理解以及特定结构变异在塑造人类生物学变异中的作用方面具有变革性。该奖项反映了NSF的法定任务，并被认为是通过基金会的智力优点和更广泛影响的审查标准来通过评估来获得支持的。

项目成果

An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice.

• DOI: 10.1126/science.abn9886
• 发表时间: 2022-10-21
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Nikkanen, Joni;Leong, Yew Ann;Krause, William C.;Dermadi, Denis;Maschek, J. Alan;Van Ry, Tyler;Cox, James E.;Weiss, Ethan J.;Gokcumen, Omer;Chawla, Ajay;Ingraham, Holly A.
• 通讯作者: Ingraham, Holly A.