Inside the biology of one of the world's highest-dwelling primates

A host of new data, including the first reference genome for this organism, is lending insights into the biology of the gelada, an Ethiopian monkey that is one of the world's highest-dwelling primates.

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Life at high altitude is challenging. Atmospheric pressure declines at higher elevations, resulting in a lower density of oxygen molecules in the air. All things being equal, each breath inhaled at high altitude takes in less oxygen, ultimately limiting the supply to organs and cells that need it to survive and function. This basic physiological problem perhaps explains why, when I first traveled to the highlands of Ethiopia, headaches and fatigue—classic signs of acute mountain sicknesskept me lagging behind the more acclimated members of our field team, especially our Ethiopian staff born and raised at high altitude. Thankfully, high-altitude biology provided a handy excuse for my poor endurance. It must have been the altitude (everyone else said so too).

Male gelada in the Simien Mountains
Male gelada in the Simien Mountains. Photograph © India Schneider-Crease.

One organism that actually thrives at high altitude is the gelada (Theropithecus gelada), a monkey found only in Ethiopia that is the last surviving vestige of a much more diverse and wide-ranging genus. The gelada is an odd primate: a grass-eating, cliff-dwelling relative of baboons (though itself not a baboon) with spectacularly fluffy hair and a conspicuous patch of red skin on the chest and neck. Restricted to montane plateaus of Ethiopia, geladas have an altitudinal range (~2,000–4,500 meters above sea level) matched by few other primates.

In 2017, the Simien Mountains Gelada Research Project started a capture-and-release program, augmenting over a decade of continuous observations of wild geladas in the Simien Mountains (3,000–4,500 meters above sea level) with high-quality measurements of body dimensions, blood markers, and DNA. This combined perspective is enabling fresh insights into the biology of geladas in their natural environment. In our new paper, published in Nature Ecology & Evolution, my colleagues and I drew on this trove of data to explore high-altitude adaptations in geladas.

Simien Mountains Gelada Research Project
The Simien Mountains Gelada Research Project (left, photograph © Shayna Liberman) has continuously observed a population of geladas in Northern Ethiopia since 2005 and, in 2018, sequenced and assembled the genome of an adult female gelada (“DIX”, right, photograph © Simien Mountains Gelada Research Project).

Our first goal was to sequence and assemble the first gelada reference genome from a female in the Simien Mountains, which we would then compare to genomes from other mammals to identify genetic adaptations to high altitude. Our research took a turn, however, when we stumbled upon an extra chromosome in her genome. The seventh chromosome (chr7) had apparently split into two, resulting in new chromosomes we refer to as chr7a and chr7b. Because this and other types of chromosomal differences tend to lead to diminished fertility, and because chromosome counts are extremely stable among monkey species most closely related to geladas, we initially believed that this must be an anomaly. As we expanded our search, however, we instead found that all sampled geladas from the Simien Mountains in Northern Ethiopia had a split chr7, indicating that it was not an outlier but rather the dominant chromosomal arrangement in Simien Mountain geladas.

Gelada karyotypes and distribution map
G-banded chromosome staining (left) shows the fissioned chromosome 7 (chr7) in Northern geladas compared to the intact chr7 in Central geladas. A distribution map (right) shows the geographic limits of three gelada populations in Ethiopia.

Even stranger, when we surveyed geladas originating from Central Ethiopia, we found that they consistently had an intact chr7, the typical and ancestral variant. In the wild, geladas from Central Ethiopia are geographically isolated from geladas in Northern Ethiopia and do not interbreed. From zoos, however, we found two individuals that likely descended from captive interbreeding—both of these geladas had mixed chromosomes (one intact and one split chr7). These individuals continue to fascinate us, as their mixed chromosomes suggest possible obstacles to reproduction. Indeed, both of them never reproduced despite having the opportunity to do so. Together, our data suggest that chr7 has evolved to distinguish geladas of Northern Ethiopia from those of Central Ethiopia, and may provide a glimpse into chromosomal processes underlying the birth of new species.

After a bonus chromosome led us down some twists and turns, we found our way back to our original aim of identifying high-altitude adaptations. Our newly assembled genome allowed us to search for changes to protein sequences that might compensate for low oxygen at high altitude. We first wondered whether gelada hemoglobins (the oxygen-carrying proteins in red blood cells) bind oxygen more efficiently, allowing them to transport more of the limited supply available in the air. Surprisingly, however, despite having unique mutations in the amino acid sequence in one hemoglobin subunit, gelada hemoglobins did not bind oxygen more efficiently in laboratory experiments.

Hemoglobin-oxygen affinity in geladas
Despite having unique substitutions in the alpha-chain subunit (left), gelada hemoglobin does not appear to have higher hemoglobin-oxygen binding affinity when compared to that of baboons or humans (right).

When we expanded our analysis to all protein-coding genes showing accelerated changes in geladas, we found that such genes tended to be involved in functions classically linked to high-altitude adaptation, including oxygen sensing and response to oxidative stress. Several genes identified by our analysis overlapped with candidate genes identified in other studies of high-altitude-living humans, livestock (e.g., sheep), and wildlife (e.g., rhesus macaques), indicating that evolution may have acted on the same genes multiple times in multiple organisms.

A typical response to low oxygen is to increase the production of red blood cells, thereby increasing the concentration of potential oxygen-carrying hemoglobin in the bloodstream. This response is adaptive, but only to a point, as red blood cells increase blood viscosity and can lead to problems with blood flow, counterproductively interfering with the transport of oxygen. In humans, this is a major component of chronic mountain sickness. We found that geladas in the Simien Mountains do not have a higher hemoglobin concentration compared to geladas housed in zoos. In this respect, high-altitude geladas resemble the classic phenotype exhibited by altitude-adapted Tibetan peoples, who maintain relatively low hemoglobin concentrations at high altitude. Our results suggest that geladas are able to maintain adequate delivery of oxygen without increasing blood-hemoglobin concentrations (snow leopards seem to be doing this too).

Gelada hemoglobin concentrations
Geladas in the Simien Mountains (~3,250 meters above sea level) do not exhibit the expected altitude-associated increases in hemoglobin concentration.

One way that geladas might accomplish this is by increasing their lung sizes, thereby maximizing their lung surface area for more efficient oxygen exchange. In support of this hypothesis, we found that geladas have a distinctly “barrel-chested” appearance, with relative chest circumferences (a stand-in for lung size) larger than those of baboons. It is not yet clear whether this trait is genetically based—that would require a separate study of chest sizes in zoo geladas—but it nevertheless may function as an additional adaptation to high-altitude gelada living.

Gelada chest circumferences
Geladas appear barrel-chested (left, photograph © India Schneider-Crease), and in fact have larger relative chest circumferences compared to baboons at low altitude (right).

Our work offers numerous novel insights into gelada high-altitude biology, but leaves several tantalizing questions unanswered. Do the candidate genomic modifications identified in our study alter function? How? Without increasing either the oxygen-binding affinity or concentration of blood hemoglobins, how are geladas maintaining adequate oxygen delivery to cells and tissues? What role have chromosome differences played in divergence between gelada populations? What is the deal with the Southern population of geladas, which we were unable to sample for this study? How can I better adapt to life at high altitude? Moving forward, we are tackling these questions and more as we seek to better understand one of our most extreme nonhuman cousins.

References

Chiou, K. L. et al. Genomic signatures of high-altitude adaptation and chromosomal polymorphism in geladas. Nat. Ecol. Evol. 6, 630–643 (2022). https://doi.org/10.1038/s41559-022-01703-4

Kenneth Chiou

Postdoctoral Associate, Arizona State University

I am interested in the variegated information encoded in genomes and how it sheds light on evolution and health in primates. My research combines tools and perspectives from evolutionary biology, anthropology, genomics, and geroscience to investigate mechanisms underlying links between the environment, aging, health, and survival.