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Lessons in hypoxic adaptation from high-altitude populations

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Abstract

An increase in hemoglobin level is seen in virtually all lowlanders who move to or train at altitude; however, studies of high-altitude native populations illustrate that this response is not necessary for successful long-term residence. Indigenous populations living at the same altitude have differences not only in hemoglobin level but also in other traits like oxygen saturation. Support for a genetic causation for differences in features of oxygen transport, namely hemoglobin levels and oxygen saturation, is derived from kindred studies among the highlander populations. Indeed, evidence from Tibet suggests that inferred genes for high oxygen saturation are associated with higher offspring survival. It may be that signaling molecules like nitric oxide and transcription factors such as hypoxia-inducible factor could act as an upstream regulator for highlander traits. However, the preponderance of data suggests that it is unlikely that one process or even a common set of processes is responsible for successful biologic adaptation shown in all three resident high-altitude populations. Future studies will require the ability to identify combinations of genetic variants with outcomes including expression levels, appropriate phenotypes, and functional responses.

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References

  1. Beall CM (2006) Andean, Tibetan, and Ethiopian patterns of adaptations to high-altitude hypoxia. Integr Comp Biol 46(1):18–24

    Article  Google Scholar 

  2. Ward MP, Milledge JS, West JB (2000) High altitude medicine and physiology. Oxford University Press, London

    Google Scholar 

  3. Moore LG, Shriver M, Bemis L et al (2004) Maternal adaptation to high-altitude pregnancy: an experiment of nature—a review. Placenta 25 (Supplement A) Trophoblast Research, vol. 18: S60–S71

  4. Wu T, Li S, Ward MP (2005) Tibetans at extreme altitude. Wilderness Environ Med 16(1):47–54

    Article  PubMed  Google Scholar 

  5. Hochachka PW, Gunga HC, Kirsch K (1998) Our ancestral physiological phenotype: an adaptation for hypoxia tolerance and for endurance performance? Proc Natl Acad Sci USA 95(4):1915–1920

    Article  PubMed  CAS  Google Scholar 

  6. Hochachka PW (1998) Mechanism and evolution of hypoxia-tolerance in humans. J Exp Biol 201(Pt 8):1243–1254

    PubMed  CAS  Google Scholar 

  7. Leon-Velarde F, Maggiorini M, Reeves JT et al (2005) Consensus statement on chronic and subacute high altitude diseases. High Alt Med Biol 6(2):147–157

    Article  PubMed  Google Scholar 

  8. Beall CM (2001) Adaptations to Altitude: A Current Assessment. Annu Rev Anthropol 30:423–446

    Article  Google Scholar 

  9. Beall CM, Decker MJ, Brittenham GM, Kushner I, Gebremedhin A, Strohl KP (2002) An Ethiopian pattern of human adaptation to high-altitude hypoxia. Proc Natl Acad Sci USA 99(26):17215–17218

    Article  PubMed  CAS  Google Scholar 

  10. Beall CM, Brittenham GM, Strohl KP et al (1998) Hemoglobin concentration of high-altitude Tibetans and Bolivian Aymara. Am J Phys Anthropol 106:385–400

    Article  PubMed  CAS  Google Scholar 

  11. Beall CM, Brittenham GM, Strohl KP et al (1997) Ventilation and hypoxic ventilatory response of Tibetan and Aymara high altitude natives. Am J Phys Anthropol 104:427–447

    Article  PubMed  CAS  Google Scholar 

  12. Beall CM (2000) Tibetan and Andean contrasts in adaptation to high-altitude hypoxia. In: Lahiri S, Prabhakar NR, Forster RE II (eds) Oxygen Sensing: Molecule to Man. Kluwer/Plenum, New York, pp 63–74

    Google Scholar 

  13. Beall CM, Song K, Elston RC, Goldstein MC (2004) Higher offspring survival among Tibetan women with high oxygen saturation genotypes residing at 4,000 m. Proc Natl Acad Sci USA 101(39):14300–14304

    Article  PubMed  CAS  Google Scholar 

  14. Strohl KP, Beall CM, Decker MJ, Brittenham G, Blangero J, Williams-Blangero S (1995) Quantitative genetic analysis of hypoxic ventilatory response at 4000 m. Respir Crit Care Med 151(4):A634

    Google Scholar 

  15. Beall CM, Blangero J, Williams-Blangero S, Goldstein MC (1994) A major gene for percent of oxygen saturation of arterial hemoglobin in Tibetan highlanders. Am J Phys Anthropol 95:271–276

    Article  PubMed  CAS  Google Scholar 

  16. Firschein IL (1961) Population dynamics of the sickle-cell trait in the black Caribs of British Honduras, Central America. Am J Hum Genet 13:233–254

    PubMed  CAS  Google Scholar 

  17. Raymond J, Segre D (2006) The effect of oxygen on biochemical networks and the evolution of complex life. Science 311(5768):1764–1767

    Article  PubMed  CAS  Google Scholar 

  18. Cerretelli P (1992) Muscle energetics and ultrastructure in chronic hypoxia. Respiration 59(Suppl 2):24–29

    Article  PubMed  Google Scholar 

  19. Beall CM (2007) Detecting natural selection in high-altitude populations. Respir Physiol Neurobiol 158(2–3):161–171

    Article  PubMed  Google Scholar 

  20. Kumar R, Qadar Pasha MA, Khan AP et al (2003) Association of high-altitude systemic hypertension with the deletion allele-of the angiotensin-converting enzyme (ACE) gene. Int J Biometeorol 48(1):10–14

    Article  PubMed  Google Scholar 

  21. Tsianos G, Eleftheriou KI, Hawe E et al (2005) Performance at altitude and angiotensin I-converting enzyme genotype. Eur J Appl Physiol 93(5–6):630–633

    Article  PubMed  CAS  Google Scholar 

  22. Morrell NW, Sarybaev AS, Alikhan A, Mirrakhimov MM, Aldashev AA (1999) ACE genotype and risk of high altitude pulmonary hypertension in Kyrghyz highlanders. Lancet 353:814March 6

    Article  PubMed  CAS  Google Scholar 

  23. Suzuki K, Kizaki T, Hitomi Y et al (2003) Genetic variation in hypoxia-inducible factor 1alpha and its possible association with high altitude adaptation in Sherpas. Med Hypotheses 61(3):385–389

    Article  PubMed  CAS  Google Scholar 

  24. Qadar Pasha MA, Khan AP, Kumar R et al (2001) Angiotensin converting enzyme insertion allele in relation to high altitude adaptation. Ann Hum Genet 65(Pt 6):531–536

    Article  PubMed  CAS  Google Scholar 

  25. Rupert J, Devine D, Monsalve M, Hochachka P (1997) Angiotensin-converting enzyme (ACE) alleles in the Quechua, a high altitude South American native population. Ann Hum Biol 26(4):375–380

    Article  Google Scholar 

  26. Cerra MC, Pellegrino D (2007) Cardiovascular cGMP-generating systems in physiological and pathological conditions. Curr Med Chem 14(5):585–599

    Article  PubMed  CAS  Google Scholar 

  27. Vaughan DJ, Brogan TV, Kerr ME, Deem S, Luchtel DL, Swenson ER (2003) Contributions of nitric oxide synthase isozymes to exhaled nitric oxide and hypoxic pulmonary vasoconstriction in rabbit lungs. Am J Physiol Lung Cell Mol Physiol 284(5):L834–843

    PubMed  CAS  Google Scholar 

  28. Beall CM, Laskowski D, Strohl KP et al (2001) Pulmonary nitric oxide in mountain dwellers. Nature 414(6862):411–412

    Article  PubMed  CAS  Google Scholar 

  29. Hoit BD, Dalton ND, Erzurum SC, Laskowski D, Strohl KP, Beall CM (2005) Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders. J Appl Physiol 99(5):1796–1801

    Article  PubMed  CAS  Google Scholar 

  30. Fagan KA, Morrissey B, Fouty BW et al (2001) Upregulation of nitric oxide synthase in mice with severe hypoxia-induced pulmonary hypertension. Respir Res 2(5):306–313

    Article  PubMed  CAS  Google Scholar 

  31. Sumbayev VV, Yasinska IM (2007) Mechanisms of hypoxic signal transduction regulated by reactive nitrogen species. Scand J Immunol 65(5):399–406

    Article  PubMed  CAS  Google Scholar 

  32. Kiang JG, Tsen KT (2006) Biology of hypoxia. Chin J Physiol 49(5):223–333

    PubMed  CAS  Google Scholar 

  33. Nisoli E, Clementi E, Carruba MO, Moncada S (2007) Defective mitochondrial biogenesis: a hallmark of the high cardiovascular risk in the metabolic syndrome? Circ Res 100(6):795–806

    Article  PubMed  CAS  Google Scholar 

  34. Hochachka P, Rupert J (2003) Fine tuning the HIF-1 ‘global’ O2 sensor for hypobaric hypoxia in Andean high-altitude natives. BioEssays 25(5):515–519

    Article  PubMed  CAS  Google Scholar 

  35. Appenzeller O, Miako T, Qualls C et al (2006) Gene expression, autonomic function and chronic hypoxia: lessons from the Andes. Clin Auton Res 16:217–222

    Article  PubMed  Google Scholar 

  36. Gao W, Gao Y, Zhang G, Song L, Sun B, Shi J (2005) Hypoxia-induced expression of HIF-1alpha and its target genes in umbilical venous endothelial cells of Tibetans and immigrant Han. Comp Biochem Physiol C Toxicol Pharmacol 141(1):93–100

    Article  PubMed  CAS  Google Scholar 

  37. Brutsaert TD, Parra EJ, Shriver MD et al (2003) Spanish genetic admixture is associated with larger V(O2) max decrement from sea level to 4338 m in Peruvian Quechua. J Appl Physiol 95(2):519–528

    PubMed  Google Scholar 

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Correspondence to Kingman P. Strohl.

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Strohl, K.P. Lessons in hypoxic adaptation from high-altitude populations. Sleep Breath 12, 115–121 (2008). https://doi.org/10.1007/s11325-007-0135-9

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