title: High altitude genetic adaptation in Tibetans: no role of increased hemoglobin-oxygen affinity.
abstract: High altitude exerts selective evolutionary pressure primarily due to its hypoxic environment, resulting in multiple adaptive responses. High hemoglobin-oxygen affinity is postulated to be one such adaptive change, which has been reported in Sherpas of the Himalayas. Tibetans have lived on the Qinghai-Tibetan plateau for thousands of years and have developed unique phenotypes, such as protection from polycythemia which has been linked to PDH2 mutation, resulting in the downregulation of the HIF pathway. In order to see if Tibetans also developed high hemoglobin-oxygen affinity as a part of their genetic adaptation, we conducted this study assessing hemoglobin-oxygen affinity and their fetal hemoglobin levels in Tibetan subjects from 3 different altitudes. We found normal hemoglobin-oxygen affinity in all subjects, fetal hemoglobin levels were normal in all except one and no hemoglobin variants in any of the subjects. We conclude that increased hemoglobin-oxygen affinity or increased fetal hemoglobin are not adaptive phenotypes of the Tibetan highlanders.
authors.affiliation: Division of Hematology, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT, USA.
authors.forename: Tsewang
authors.initials: T
authors.lastname: Tashi
authors.affiliation: Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai Province, China.
authors.forename: Tang
authors.initials: T
authors.lastname: Feng
authors.affiliation: Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.
authors.forename: Parvaiz
authors.initials: P
authors.lastname: Koul
authors.affiliation: National Academy of Sciences, Cell Biology Unit, San Andres University School of Medicine, La Paz, Bolivia.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Amaru
authors.affiliation: ARUP Laboratories, Salt Lake City, UT, USA.
authors.forename: Dottie
authors.initials: D
authors.lastname: Hussey
authors.affiliation: Division of Hematology, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT, USA.
authors.forename: Felipe R
authors.initials: FR
authors.lastname: Lorenzo
authors.affiliation: Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai Province, China.
authors.forename: Ge
authors.initials: G
authors.lastname: RiLi
authors.affiliation: Division of Hematology, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT, USA; ARUP Laboratories, Salt Lake City, UT, USA. Electronic address: josef.prchal@hsc.utah.edu.
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D000328:Adult; D000368:Aged; D000531:Altitude; D044466:Asian People / Q000235:genetics; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D010092:Oximetry; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D018609:Tibet; D014481:United States
chemical_list: D006454:Hemoglobins; D010100:Oxygen
keywords: Fetal hemoglobin; Hemoglobin–oxygen affinity; Hypoxia; P(50)