Hemoglobin-oxygen affinity in high-altitude vertebrates: Is there evidence for an adaptive trend?

Jay F. Storz

Research output: Contribution to journalReview articlepeer-review

78 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3190-3203
Number of pages14
JournalJournal of Experimental Biology
Issue number20
StatePublished - Oct 15 2016


  • Biochemical adaptation
  • Blood oxygen transport
  • Hemoglobin
  • High-altitude adaptation
  • Hypoxia
  • Physiological adaptation

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Physiology
  • Aquatic Science
  • Animal Science and Zoology
  • Molecular Biology
  • Insect Science


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