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

高海拔地区的生活伴随着许多生理挑战，包括暴露在低氧水平和低温下。因此，大多数生活在高海拔地区的动物都在强烈的选择下发展适应这些环境挑战的能力。确定生活在高海拔地区的动物（包括非人类灵长类动物）的适应性，可以帮助阐明许多特征的适应性进化机制。这个项目的中心目标是在一种新的非人类灵长类动物——狒狒身上识别出这些适应性。这一发现将推进我们对遗传变化如何导致一个重要的灵长类模式系统适应高海拔的认识。该项目将为博士后、研究生和本科生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。该项目结合了进化生物学、基因组学、分子生物学和生物人类学的理论和工具，为研究非人类灵长类动物对高海拔环境的遗传适应提供了一个创新的、强大的、多学科的框架。该项目有两个目的：(1)生成并使用一个注释良好的狒狒基因组和调控图谱，以确定与它们的近亲相比，狒狒猴经历了基因扩增和正选择的基因家族；(2)确定在高海拔狒狒中显示正选择特征的候选位点。该项目将确定基因和家族扩展，这些基因和家族扩展在高海拔适应中所起的作用以前是未知的或知之甚少的。该项目还代表了从非侵入性样本中对动物基因组进行测序的尖端技术的应用，从而鼓励对历史上受样本可用性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，使灵长类近亲能够在缺氧和寒冷的环境中茁壮成长，该项目也可能对理解氧气摄入和运输受损的人类疾病具有转化意义。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.