Hemoglobin-oxygen Affinity in High-Altitude Vertebrates: Is There Evidence for an Adaptive Trend?

J Exp Biol. 2016 Oct 15;219(Pt 20):3190-3203. doi: 10.1242/jeb.127134.


In air-breathing vertebrates at high altitude, fine-tuned adjustments in hemoglobin (Hb)-O2 affinity provide an energetically efficient means of mitigating the effects of arterial hypoxemia. However, it is not always clear whether an increased or decreased Hb-O2 affinity should be expected to improve tissue O2 delivery under different degrees of hypoxia, due to the inherent trade-off between arterial O2 loading and peripheral O2 unloading. Theoretical results indicate that the optimal Hb-O2 affinity varies as a non-linear function of environmental O2 availability, and the threshold elevation at which an increased Hb-O2 affinity becomes advantageous depends on the magnitude of diffusion limitation (the extent to which O2 equilibration at the blood-gas interface is limited by the kinetics of O2 exchange). This body of theory provides a framework for interpreting the possible adaptive significance of evolved changes in Hb-O2 affinity in vertebrates that have colonized high-altitude environments. To evaluate the evidence for an empirical generalization and to test theoretical predictions, I synthesized comparative data in a phylogenetic framework to assess the strength of the relationship between Hb-O2 affinity and native elevation in mammals and birds. Evidence for a general trend in mammals is equivocal, but there is a remarkably strong positive relationship between Hb-O2 affinity and native elevation in birds. Evolved changes in Hb function in high-altitude birds provide one of the most compelling examples of convergent biochemical adaptation in vertebrates.

Keywords: Biochemical adaptation; Blood oxygen transport; Hemoglobin; High-altitude adaptation; Hypoxia; Physiological adaptation.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Physiological*
  • Altitude*
  • Animals
  • Hemoglobins / metabolism*
  • Hypoxia / physiopathology
  • Oxygen / metabolism*
  • Vertebrates / physiology*


  • Hemoglobins
  • Oxygen