Evolution, adaptation and structure-function relationships of extinct and extant mammalian hemoglobins: mechanisms of allosteric interactions and their interplay with temperature

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Directly linking external environmental conditions with cellular metabolic processes, vertebrate hemoglobins are exquisitely tailored to balance the uptake of oxygen at the lungs and its delivery to the tissues. While the heme groups (the loci for oxygen binding) of all hemoglobins are identical, the globin composition can vary substantially between species. Seemingly small changes in the amino acid composition, resulting from base substitutions with the DNA of the globin chains, can have profound effects on the protein's oxygen-binding characteristics and sensitivity to temperature. These alterations have undoubtedly played a key role in the ability of mammals to occupy a diverse range of habitats, yet little is known regarding their precise molecular mechanisms and mode of evolution. This application is for funds to support novel research on hemoglobins from extinct and extant mammals specialized to life in arctic, semi-aquatic and subterranean environments, focusing specifically on the oxygen binding characteristics of these respiratory proteins in response to temperature and other red cell ligands (carbon dioxide, protons, chloride ions and certain organic phosphates).     These studies constitute basic science that addresses fundamental issues pertaining the form, function and evolution of this biologically important molecule. Technical training will expose students to recently developed techniques relating to the evolution, expression and analyses of respiratory proteins, and impart skills in molecular biology, genetics and computation, producing personnel highly qualified for employment in academia and Canada's rapidly growing medically based pharmaceutical and biotechnology sectors. Finally, insights gained from this research programme may have important applied perspectives in the development of hemoglobin-based blood substitutes with specially engineered properties. The advent of this technology is increasingly attractive in the face of increasing concern over the transmission of viral (HIV, hepatitis, West Nile) and other contaminants via donor blood.