Genetically based low oxygen affinities of felid hemoglobins: Lack of biochemical adaptation to high-altitude hypoxia in the snow leopard

Authors

Jan E. Janecka, Duquesne University, PittsburghFollow
Simone S. E. Nielsen, Aarhus University
Sidsel D. Andersen, Aarhus University
Federico G. Hoffmann, University of Nebraska-LincolnFollow
Roy E. Weber, Aarhus UniversityFollow
Trevor Anderson, Duquesne University, Pittsburgh
Jay F. Storz, University of Nebraska-LincolnFollow
Angela Fago, Aarhus University, DenmarkFollow

Date of this Version

2015

Citation

The Journal of Experimental Biology (2015) 218, 2402-2409 doi:10.1242/jeb.125369

Comments

© 2015. Published by The Company of Biologists Ltd. Used by permission.

Abstract

Genetically based modifications of hemoglobin (Hb) function that increase blood–O₂ affinity are hallmarks of hypoxia adaptation in vertebrates. Among mammals, felid Hbs are unusual in that they have low intrinsic O₂ affinities and reduced sensitivities to the allosteric cofactor 2,3-diphosphoglycerate (DPG). This combination of features compromises the acclimatization capacity of blood–O2 affinity and has led to the hypothesis that felids have a restricted physiological niche breadth relative to other mammals. In seeming defiance of this conjecture, the snow leopard (Panthera uncia) has an extraordinarily broad elevational distribution and occurs at elevations above 6000 m in the Himalayas. Here, we characterized structural and functional variation of big cat Hbs and investigated molecular mechanisms of Hb adaptation and allosteric regulation thatmay contribute to the extreme hypoxia tolerance of the snow leopard. Experiments revealed that purified Hbs from snow leopard and African lion exhibited equally low O₂ affinities and DPG sensitivities. Both properties are primarily attributable to a single amino acid substitution, β2His→Phe, which occurred in the common ancestor of Felidae. Given the low O₂ affinity and reduced regulatory capacity of feline Hbs, the extreme hypoxia tolerance of snow leopards must be attributable to compensatory modifications of other steps in the O₂-transport pathway.