Allosteric mechanisms underlying the adaptive increase in hemoglobin–oxygen affinity of the bar-headed goose

Agnieszka Jendroszek, Hans Malte, Cathrine B. Overgaard, Kristian Beedholm, Chandrasekhar Natarajan, Roy E. Weber, Jay F. Storz, Angela Fago

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The high blood–O2affinity of the bar-headed goose (Anser indicus) is an integral component of the biochemical and physiological adaptations that allow this hypoxia-tolerant species to undertake migratory flights over the Himalayas. The high blood–O2affinity of this species was originally attributed to a single amino acid substitution of the major hemoglobin (Hb) isoform, HbA, which was thought to destabilize the low-affinity T state, thereby shifting the T–R allosteric equilibrium towards the high-affinity R state. Surprisingly, this mechanistic hypothesis has never been addressed using native proteins purified from blood. Here, we report a detailed analysis of O2equilibria and kinetics of native major HbA and minor HbD isoforms from bar-headed goose and greylag goose (Anser anser), a strictly lowland species, to identify and characterize the mechanistic basis for the adaptive change in Hb function. We find that HbA and HbD of bar-headed goose have consistently higher O2affinities than those of the greylag goose. The corresponding Hb isoforms of the two species are equally responsive to physiological allosteric cofactors and have similar Bohr effects. Thermodynamic analyses of O2equilibrium curves according to the two-state Monod–Wyman–Changeaux model revealed higher R-state O2affinities in the bar-headed goose Hbs, associated with lower O2dissociation rates, compared with the greylag goose. Conversely, the T state was not destabilized and the T–R allosteric equilibrium was unaltered in bar-headed goose Hbs. The physiological implication of these results is that increased R-state affinity allows for enhanced O2saturation in the lungs during hypoxia, but without impairing O2delivery to tissues.

Original languageEnglish (US)
Article numberjeb185470
JournalJournal of Experimental Biology
Issue number18
StatePublished - Sep 2018


  • Adaptation
  • Allostery
  • Blood
  • High-altitude
  • Hypoxia
  • Oxygen transport

ASJC Scopus subject areas

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


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