Human genetic adaptation to high altitudes: Current status and future prospects

Abstract

The question of whether human populations have adapted genetically to high altitude has been of interest since studies began there in the early 1900s. Initially there was debate as to whether genetic adaptation to high altitude has taken place based, in part, on disciplinary orientation and the sources of evidence being considered. Studies centered on short-term responses, termed acclimatization, and the developmental changes occurring across lifetimes. A paradigm shift occurred with the advent of single nucleotide polymorphism (SNP) technologies and statistical methods for detecting evidence of natural selection, resulting in an exponential rise in the number of publications reporting genetic adaptation. Reviewed here are the various kinds of evidence by which adaptation to high altitude has been assessed and which have led to widespread acceptance of the idea that genetic adaptation to high altitude has occurred. While methodological and other challenges remain for determining the specific gene or genes involved and the physiological mechanisms by which they are exerting their effects, considerable progress has been realized as shown by recent studies in Tibetans, Andeans and Ethiopians. Further advances are anticipated with the advent of new statistical methods, whole-genome sequencing and other molecular techniques for finer-scale genetic mapping, and greater intradisciplinary and interdisciplinary collaboration to identify the functional consequences of the genes or gene regions implicated and the time scales involved.

Population Structure, and Selection Signatures Underlying High-Altitude Adaptation Inferred From Genome-Wide Copy Number Variations in Chinese Indigenous Cattle

“…Studies have shown that maladaptive phenotypes about the circulatory systems that are related to the absorption and delivery of O 2 , such as increases in concentration of hemoglobin and erythrocytes, elevated pulmonary blood pressure (derived from vasoconstriction), and right-ventricle hypertrophy, are ubiquitous in low-altitude mammals when exposed to hypoxia (Tucker and Rhodes, 2001;Storz et al, 2010;Velotta et al, 2018), and low-altitude cattle are hyper-responders to high altitude (Tucker and Rhodes, 2001). Conversely, many high-altitude populations adapt well to hypoxia and exhibit a physiological reaction similar to lowaltitude mammals with normal pulmonary blood pressure, right-ventricle size, and erythrocyte concentration, which can be referred to the effects of selection on genetically based trait variation that suppresses or eliminates these maladaptive phenotypes (Storz et al, 2010;Moore, 2017;Velotta et al, 2018). Hypoxia-inducible factors (HIFs) have been demonstrated to play a central role in the adaptive response to hypoxia by regulating expression of hypoxia-dependent genes that can increase systemic O 2 delivery or improve cellular metabolic adaptation (Semenza, 2000;Covello and Simon, 2004;Taylor, 2008).…”

New insights into early MIS 5 lithic technological behavior in the Levant: Nesher Ramla, Israel as a case study

“…To date, the only mid-MP lithic data set described in detail derives from Qafzeh Cave [14]. Skhul Cave, Tabun layer C as well as Naamé, Nahr Ibrahim, and Ras El-Kelb in Lebanon are the other sites that were mentioned to represent this period [15][16][17][18][19][20][21]. The centripetal assemblages at Qafzeh and Skhul Caves are associated with the remains of H. sapiens [20,[22][23][24][25].…”

“…Skhul Cave, Tabun layer C as well as Naamé, Nahr Ibrahim, and Ras El-Kelb in Lebanon are the other sites that were mentioned to represent this period [15][16][17][18][19][20][21]. The centripetal assemblages at Qafzeh and Skhul Caves are associated with the remains of H. sapiens [20,[22][23][24][25]. The rapid accumulation of archaeological evidence from the northeastern Africa, the Arabian Peninsula, and the Levant suggests that early MIS 5 dispersals associated with the centripetal Levallois technology were a well-established phenomenon [26][27][28][29][30][31][32].…”

“…The paleoanthropological evidence suggests that MIS 5 human population in the Near East possibly represents one or several expansions of H. sapiens out of Africa [14,20,22,29,31,33,34]. In line with the paleoanthropological evidence, recent paleoenvironmental studies, including speleothem deposition, climatic modeling, and paleohydrology reconstructions in the Levant and Arabia have demonstrated that periods within MIS 5 were more humid, with an increase in temperatures and rainfall, which may have created "climatic windows of opportunity" for the hominid groups leaving Africa [35][36][37][38][39][40][41][42][43].…”

Investigation of the gene co-expression network and hub genes associated with acute mountain sickness

“…Interestingly, people who have lived on the plateau for a long time can adapt to such a low-oxygen environment. These people are thought to be more adapted to such an oxygen-deficient environment after years of genetic selection [10,11]. The adaptation e has been speculated to be related to multiple genes.…”