Evolution of haemoglobin function: molecular adaptations to environment.

1. Nearly 1000 mutations have been described for human haemoglobin (Hb), many of which result in subtle changes to the oxygen transport system. Similar changes have occurred over the course of animal evolution resulting in a diversity of functional attributes which appear to correlate the availability of oxygen in the environment with metabolic demand. 2. At an early stage in evolution, worm-like animals had large, polymeric aggregations of Hb subunits circulating through primitive circulatory systems and some possessed monomeric Hb in blood cells functioning as an oxygen store. 3. The circulating vertebrate red blood cell provides an environment allowing haem units to interact among themselves and with various organic phosphates to allow a responsive and highly regulated system of gas transport. During metazoan evolution the burden of physiological regulation has shifted from the cells to organ systems, as endothermy and aerial breathing permit a relatively constant environment. 4. An understanding of the adaptive possibilities of Hb has helped us to understand the ontogeny of oxygen transport and to interpret recently described functional properties of human embryonic haemoglobins.