Functional genomics of high-altitude adaptation in a non-human primate model

非人类灵长类动物模型高海拔适应的功能基因组学

• 批准号: 2010309
• 负责人: Noah Snyder-Mackler
• 金额: $ 39.4万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2010309&HistoricalAwards=false
• 关键词: Functional; genomics; altitude; adaptation; non

Life at high altitude is associated with many physiological challenges, including exposure to low oxygen levels and cold temperatures. Consequently, most animals living at high altitude have been under strong selection to develop adaptations to these environmental challenges. Identifying adaptations in high-altitude-living animals, including non-human primates, could help illuminate the mechanisms underlying adaptive evolution of many traits. The central goal of this project is to identify these adaptations in a novel non-human primate model, the gelada monkey. The findings will advance our knowledge of how genetic changes lead to high-altitude adaptations in an important primate model system. The project will provide rigorous scientific training at the postdoctoral, graduate, and undergraduate levels. The investigators will also engage in public outreach and international research collaborations, contributing to scientific education and conservation efforts both domestically and abroad.This project provides an innovative, robust, and multi-disciplinary framework, combining theories and tools from evolutionary biology, genomics, molecular biology, and biological anthropology, to investigate genetic adaptations to high altitude in a non-human primate. The project has two aims: (1) to generate and use a well-annotated gelada genome and regulatory map to identify gene families that have undergone gene expansion and genes under positive selection in gelada monkeys compared to their close phylogenetic relatives, and (2) to identify candidate loci that show signatures of positive selection in high-altitude geladas. The project will identify genes and family expansions whose role in high-altitude adaptations was previously unknown or poorly understood. The project also represents the application of cutting-edge techniques for the sequencing of animal genomes from non-invasive samples, thereby encouraging genomic analyses in wild organisms historically constrained by sample availability. Recent advances in high throughput genomic technologies, including the approaches the PI and co-PI have developed, have allowed researchers to identify genes and loci under selection in captivity and the wild. Together, the results of these studies will generate new hypotheses and predictions for high-altitude and other adaptations in humans and other animals through identification of genetic variants in a novel system. By identifying novel molecular changes that allow a close primate relative to thrive in hypoxic and cold environments, this project may also have translational implications for understanding human diseases of impaired oxygen intake and transport.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.

高海拔生活与许多生理挑战有关，包括暴露于低氧水平和低温。因此，大多数生活在高海拔地区的动物都受到了强有力的选择，以适应这些环境挑战。识别高海拔生活的动物（包括非人类灵长类动物）的适应性，可以帮助阐明许多特征适应性进化的机制。该项目的中心目标是在一种新的非人类灵长类动物模型--狮尾猴中识别这些适应性。这些发现将推进我们对遗传变化如何导致重要灵长类模型系统的高海拔适应的认识。该项目将在博士后、研究生和本科生层面提供严格的科学培训。该项目将提供一个创新的、强大的、多学科的框架，结合进化生物学、基因组学、分子生物学和生物人类学的理论和工具，研究非人类灵长类动物对高海拔的遗传适应。该项目有两个目标：（1）生成并使用注释良好的狮尾狒狒基因组和调控图谱，以鉴定与其亲缘关系密切的亲缘动物相比在狮尾狒狒猴中经历了基因扩增和正选择的基因家族，以及（2）鉴定在高海拔狮尾狒狒中显示正选择特征的候选基因座。该项目将确定基因和家族扩展，其在高海拔适应中的作用以前是未知的或知之甚少。该项目还代表了应用尖端技术对非侵入性样本进行动物基因组测序，从而鼓励对历史上受样本供应限制的野生生物进行基因组分析。高通量基因组技术的最新进展，包括PI和co-PI已经开发的方法，使研究人员能够在圈养和野生环境中识别选择下的基因和位点。总之，这些研究的结果将通过识别新系统中的遗传变异，为人类和其他动物的高海拔和其他适应性产生新的假设和预测。通过识别新的分子变化，使一个密切的灵长类动物在缺氧和寒冷的环境中茁壮成长，这个项目也可能有翻译的影响，了解人类疾病的氧气摄入和运输受损。这个奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

项目成果

A novel statovirus identified in fecal samples from wild geladas in the Ethiopian highlands

• DOI: 10.1007/s00705-022-05588-3
• 发表时间: 2022-10-21
• 期刊: ARCHIVES OF VIROLOGY
• 影响因子: 2.7
• 作者: Schneider-Crease，India A.;Chiou，Kenneth L.;Varsani，Arvind
• 通讯作者: Varsani，Arvind

Maternal effects on early-life gut microbiota maturation in a wild nonhuman primate

• DOI: 10.1016/j.cub.2022.08.037
• 发表时间: 2022-10-24
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Baniel, Alice;Petrullo, Lauren;Lu, Amy
• 通讯作者: Lu, Amy

Vascularization underlies differences in sexually selected skin coloration in a wild primate

• DOI: 10.1111/mec.17026
• 发表时间: 2023-05-24
• 期刊: MOLECULAR ECOLOGY
• 影响因子: 4.9
• 作者: DeLacey, Patricia M.;Sen, Sharmi;Snyder-Mackler, Noah
• 通讯作者: Snyder-Mackler, Noah