How the Denisovan Genome Helped Tibetan and Sherpa Peoples Colonise High-Altitude Environments

Tibetan and Sherpa populations in the Himalayas have inherited, trough mixing with Denisovans , a number of genetic variants that enable them to live permanently at high altitudes. The discovery — published in the journal eLife — was made by a research team coordinated by the University of Bologna.

Researchers analysed the genomes of native ethnic groups in the Himalayan regions of Tibet and Nepal to understand the biological impact of variants introduced into their genetic makeup through hybridisation with Denisovans — an archaic human species that lived in Asia until around 30,000 years ago. The aim was to test whether these genetic variants helped address the challenges the struggles of living at high altitudes, such as the organism’s reduced ability to capture oxygen from the atmosphere.

Marco Sazzini, professor at the Department of Biological, Geological and Environmental Sciences and study coordinator, explained: “Contrary to prior claims in scientific literature, Tibetan and Sherpa populations did not adapt to high altitudes as a consequence of modifications to a single gene. Our findings show that hybridisation between the ancestors of these populations and Denisovans resulted in numerous advantageous combinations of variants typical of our and ‘archaic’ species, involving at least a dozen genes.”

We now know that we Homo sapiens coexisted with other human species over a period of time, leading to multiple episodes of genetic hybridisation that have shaped human biology to a far greater extent than previously assumed. By analysing the genome of modern populations, it is possible to identify that small percentage of genetic variants inherited from archaic species with which interbreeding took place: non-African genomes contain 1–2% Neanderthal variants, while in East Asian and Melanesia populations we can find up to 3% Denisovan variants.

Professor Sazzini added: “Very little is still known about how these ‘archaic’ variants play a role in the evolution of adaptations to different environmental conditions mediated by complex biological traits — that is, regulated by multiple genes. This study tried to identify the genetic basis of complex traits specific to Himalayan populations and to estimate how much they also included genetic variants specific to Denisovans.”

Researchers then mapped the genome of Tibetan ancestral populations living above 3,000 metres above sea level. Combining different analysis approaches, they identified “archaic” variants that help developing vital biological adaptations to survive at high altitudes, reducing cardiovascular risks from low blood oxygen and ensuring adequate tissue oxygenation.

Giulia Ferraretti, PhD student at the University of Bologna and lead author of the study, concluded: “Our analyses have shown how natural selection has acted in these populations on numerous combinations of human and ‘archaic’ variants, enabling the formation of new vascular structures. These adaptations ensure adequate tissue oxygenation even in the case of low blood oxygen. Additionally, they reduce the cardiovascular risks linked to oxygen deficiency, protecting against the onset of pathological traits such as ventricular preexcitation, supraventricular arrhythmias and cardiac hypertrophy.”

Funded by Fondazione Cassa di Risparmio in Bologna, the study was published in the journal eLife under the title “Archaic introgression contributed to shape the adaptive modulation of angiogenesis and cardiovascular traits in human high-altitude populations from the Himalayas.” The research group was coordinated by Marco Sazzini, professor at the Department of Biological, Geological and Environmental Sciences of the University of Bologna and member of the Alma Climate Interdepartmental Centre. Lead author of the paper is Giulia Ferraretti, PhD student in Earth, Life and Environmental Sciences. From the University of Bologna, researchers Stefania Sarno, Marta Alberti and Paolo Abondio also contributed to the study. In collaboration with Agense Dezi and Angela Corcelli of the University of Bari, Guido Alberto Gnecchi Ruscone of the Max Planck Institute for Evolutionary Anthropology in Leipzig (Germany), Luca Natali of the Italian Institute of Human Palaeontology, Phurba Tenjing Sherpa of the Mount Everest Summiters Club (Nepal) and Explora Nunaat International members Paolo Cocco, Massimiliano Tiriticco, Marco Di Marcello, Giorgio Marinelli and Davide Peluzzi.