Population History and Altitude-Related Adaptation in the Sherpa

Abstract

The first ascent of Mount Everest by Tenzing Norgay and Sir Edmund Hillary in 1953 brought global attention to the Sherpa people and human performance at altitude. The Sherpa inhabit the Khumbu Valley of Nepal, and are descendants of a population that has resided continuously on the Tibetan plateau for the past ∼25,000 to 40,000 years. The long exposure of the Sherpa to an inhospitable environment has driven genetic selection and produced distinct adaptive phenotypes. This review summarizes the population history of the Sherpa and their physiological and genetic adaptation to hypoxia. Genomic studies have identified robust signals of positive selection across EPAS1, EGLN1, and PPARA, that are associated with hemoglobin levels, which likely protect the Sherpa from altitude sickness. However, the biological underpinnings of other adaptive phenotypes such as birth weight and the increased reproductive success of Sherpa women are unknown. Further studies are required to identify additional signatures of selection and refine existing Sherpa-specific adaptive phenotypes to understand how genetic factors have underpinned adaptation in this population. By correlating known and emerging signals of genetic selection with adaptive phenotypes, we can further reveal hypoxia-related biological mechanisms of adaptation. Ultimately this work could provide valuable information regarding treatments of hypoxia-related illnesses including stroke, heart failure, lung disease and cancer.

Cross-Species Insights Into Genomic Adaptations to Hypoxia

“…The unique sets of traits exhibited by highlanders today suggest distinct population histories have shaped the adaptive and maladaptive milieu in each population, although there is notable within-population variation in several key traits. The key physiological traits exhibited by each continental population have been recently summarized (Gilbert-Kawai et al, 2014;Simonson, 2015;Moore, 2017;Bhandari and Cavalleri, 2019). On average, Tibetan and Ethiopian highlanders tend to exhibit hemoglobin concentrations that are lower relative to acclimatized sojourners and Andeans at high altitude (Beall, 2007).…”

“…The key physiological traits exhibited by each continental population have been recently summarized ( Gilbert-Kawai et al, 2014 ; Simonson, 2015 ; Moore, 2017 ; Bhandari and Cavalleri, 2019 ). On average, Tibetan and Ethiopian highlanders tend to exhibit hemoglobin concentrations that are lower relative to acclimatized sojourners and Andeans at high altitude ( Beall, 2007 ).…”

Changes in hemoglobin levels with age and altitude in preschool‐aged children in Peru: the assessment of two individual‐based national databases

“…In Peru, the population living in the Southern Andes has greater generational antiquity than the population living in the Central Andes 12 . Furthermore, two ethnic populations living in the Himalayas, the Tibetan and Han populations, have different generational antiquity at high altitudes 13,14 . Tibetan people have lived on the Qinghai‒Tibet plateau (around 4500 m) for many generations and are well adapted to the high‐altitude environment 13,14 .…”

“…12 Furthermore, two ethnic populations living in the Himalayas, the Tibetan and Han populations, have different generational antiquity at high altitudes. 13,14 Tibetan people have lived on the Qinghai-Tibet plateau (around 4500 m) for many generations and are well adapted to the highaltitude environment. 13,14 Both genetic and archeological data suggest that Tibetans have been living on the Qinghai Tibetan plateau since the late Paleolithic period (as early as approximately 30,000 years ago).…”

Being Blessed by Qomolangma: The Diversity and Local Knowledge of Wild Edible Plants Used by Chenthang Sherpa People to Treat Seasonal Food Shortage

“…As a result, people living in this area have to face rugged terrain, and the channels for the exchange of products and knowledge between the local community and the outside world are blocked. Sherpa is a cross-border ethnic group living on both sides of the Himalayas, mainly in Nepal (Solu, Khumbu Canyon) and Xizang, China (Mount Everest National Nature Reserve) [26,27]. Sherpa are known as "the Porter of the Himalayas", because they work for mountain expeditions as guides and porters.…”