Drosophila populations adapted to survive at low levels of oxygen have been selected over many generations and have been used in studies of hypoxia adaptation. Notch (N) and genes encoding or regulating the Notch pathway appear to be under selection in these populations. Knockdown or loss of function of N reduces hypoxia tolerance; gain-of function mutations enhance tolerance. Other genes that appear to be under selection, and also appear to be under positive selection in high-altitude populations, include tzn (named for Tenzing Norgay), phu (named for Phurba Tashi), plh (named for Pasang Lhamu), and Arl8.
Based on a GWAS analysis of chronic mountain sickness (CMS) and non-CMS individuals in high-altitude populations, a number of candidate genes for adaptation to long-term exposure to hypoxia were identified. These were assessed in Drosophila using the orthologous fly genes. When down-regulated via RNAi, a number of the candidate genes were observed to significantly enhance hypoxia tolerance, including orthologs of known HIF (hypoxia-inducible factor) genes such as Ulp1 (orthologous to human SENP1). In addition, orthologs of several HIF-independent genes were observed to enhance hypoxia tolerance when down-regulated: Blimp-1 (orthologous to human PRDM1) and Oseg1 (orthologous to human IFT122).
[updated Mar. 2021 by FlyBase; FBrf0222196]
[CHRONIC MOUNTAIN SICKNESS, SUSCEPTIBILITY TO](https://omim.org/entry/616182)
[CHRONIC MOUNTAIN SICKNESS, SUSCEPTIBILITY TO](https://omim.org/entry/616182)
Chronic mountain sickness (CMS), or Monge disease, represents a state of maladaptation to high-altitude hypoxia in a member of a population acclimatized to high altitudes. CMS is characterized by severe polycythemia and an array of neurologic symptoms, including headache, fatigue, somnolence, and depression. Often, people with CMS suffer from strokes and myocardial infarctions in early adulthood because of increased blood viscosity. Studies have shown that CMS is common in Andeans, found occasionally in Tibetans, and absent from the Ethiopian population living on the East African high-altitude plateau (summary by Zhou et al., 2013; pubmed:23954164). Acute mountain sickness is experienced by unacclimatized travelers exposed to high altitude.
High-scoring ortholog of human NOTCH1, NOTCH2, and NOTCH3; lower-scoring ortholog of NOTCH4.