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

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.