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

高海拔生活与许多生理挑战有关，包括暴露在低氧水平和寒冷温度下。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，以发展对这些环境挑战的适应。识别生活在高海拔地区的动物，包括非人类灵长类动物的适应能力，可能有助于阐明许多特征适应进化的机制。该项目的中心目标是在一种新的非人类灵长类动物模型--狐猴身上识别这些适应。这些发现将促进我们对基因变化如何导致在一个重要的灵长类动物模型系统中进行高海拔适应的了解。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。研究人员还将参与公共宣传和国际研究合作，为国内外的科学教育和保护工作做出贡献。该项目提供了一个创新的、强大的和多学科的框架，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Gelada基因组和调控图，以识别与其近亲系统发育相关的Gelada猕猴中经历基因扩展和正选择的基因家族，以及(2)确定在高海拔Geladas中显示正选择特征的候选基因座。该项目将确定基因和家庭扩展，它们在高海拔适应中的作用以前未知或知之甚少。该项目还代表了尖端技术的应用，用于从非侵入性样本中对动物基因组进行排序，从而鼓励对野生生物进行基因组分析，这些野生生物历来受到样本可用性的限制。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，使研究人员能够识别圈养和野生环境中选择的基因和基因座。总而言之，这些研究的结果将通过识别一个新系统中的遗传变异，对人类和其他动物的高海拔和其他适应能力产生新的假设和预测。通过识别新的分子变化，使近亲灵长类动物在低氧和寒冷环境中茁壮成长，该项目还可能对理解人类氧气摄取和运输受损的疾病具有翻译意义。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.