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

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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.