Intellectual Merit:

Life at high altitude is challenging due to many stressors, including hypoxia and cold temperatures. Consequently, most animals living at high altitude have been under strong selection to develop adaptations to these challenges. Adaptation to high altitude has thus become a classic example of natural selection acting on biological variation across species and populations–primarily in smaller, shorter-lived species like rodents and birds. This project aimed to identify novel genetic and physiological adaptations to high altitude in a larger, longer-lived species: the gelada monkey (Theropithecus gelada), which has significantly advanced our knowledge of the genetic underpinnings of high altitude adaptation across primates, including humans. 

This project generated the first gelada reference genome (Tgel_1.0) and sequenced genomes from more than 100 geladas and 20 baboons for comparative analysis. These data revealed that geladas in the northern part of their range have a different number of chromosomes compared to geladas in other parts of Ethiopia, as well as all baboons and macaques. This unexpected finding suggests that gelada should be reclassified into two distinct species rather than one since the large chromosomal variation likely reduces fertility in hybrid offspring. 

Additionally, the new genome revealed numerous structural and sequence changes that may help geladas survive at high altitudes. First, geladas possess two primate-specific changes in the protein sequence of hemoglobin, the molecule responsible for oxygen transport in the body. While these changes do not affect the oxygen-binding capacity of hemoglobin compared to other primates, they may alter its structure and stability. Second, many genes in geladas display strong signatures of natural selection, particularly those involved in the cellular response to hypoxia. Third, the genome shows rapid (or accelerated) evolution in 29 non-coding regions, which likely regulate gene expression in a tissue-specific manner. These regions are located near genes that respond to hypoxia and regulate angiogenesis. 

Together, these findings generate new hypotheses and predictions about high-altitude adaptations in humans and other animals by identifying numerous genetic variants in this unique species. By uncovering novel molecular changes that allow a close primate relative to thrive in hypoxic and cold environments, the results of this project also have important implications for understanding human diseases related to impaired oxygen intake and transport.

Broader Impacts:

This project has provided training opportunities in comparative genomics for two postdoctoral associates, one graduate student, and many undergraduate students. Specifically, as part of a four-year research experience for undergraduates (REU), this project provided hands-on training in genomics and bioinformatics to 14 undergraduates from across the US, most of whom have continued to pursue research careers in STEM. This project also provided valuable training and employment for four Ethiopian field assistants as part of the Simien Mountains Gelada Research Project. The findings were shared with academic audiences at conferences and in invited talks, as well as with the broader public both in the US and in Ethiopia, where geladas are endemic. Some of this project’s findings have been developed into high-school-level teaching material as part of a collaboration with Science Journal for Kids. Finally, this project has provided novel information on the health and development of the gelada, which will have important conservation implications for this unique species.

Last Modified: 12/30/2024
Modified by: Noah Snyder-Mackler