Kelsey Jorgensen

Human populations from the Himalayan Plateau and the Peruvian Andes have thrived in high-altitude environments for thousands of years despite the extreme environmental stress of hypoxia. Previous studies have identified hypoxia-inducible factor (HIF) pathway genes under positive selection in these two high-altitude populations that confer adaptive phenotype responses. However, the precise role of HIF signaling and its association with divergent phenotypic outcomes in these two populations is complex and still not fully understood. Here, I propose an innovative approach merging genomic, transcriptomic, and physiological data to identify putative causal variant(s) along the HIF pathway that mediate the genetic basis for protective adaptations to hypoxia. With these methods, this project will leverage the power of a comparative analysis between the Nepali Sherpa from the Himalayan Plateau and Quechua speakers from the Peruvian Andes. Furthermore, I will focus on the spleen, an organ with a primary role in red blood cell metabolism and mobilization, to clarify the role of this organ in augmented O2 carrying capacity among Nepali Sherpa at high altitudes. By harnessing multiple methods across a comparative population analysis, this project will provide greater insights into long-standing anthropological questions on human adaptation to high altitude.