Transplanting a unique allosteric effect from crocodile into human haemoglobin

Abstract

CROCODILES are able to remain under water for more than one hour without surfacing to breathe^1,2 and often kill their prey by drowning it. How do crocodiles stay under water for a long time? When they hold their breath, bicarbonate ions, the final product of respiration, accumulate and drastically reduce the oxygen affinity of haemoglobin, releasing a large fraction of haemoglobin-bound oxygen into the tissues^3,4. We have now located the bicarbonate-ion-binding site at the α₁β₂-subunit interface by making various human-crocodile chimaeric haemoglobins. Furthermore, we have been able to transplant the bicarbonate effect into human haemoglobin by replacing only a few residues, even though the amino-acid sequence identity between crocodile (Crocodylus niloticus) and human haemoglobins is only 68% for the α- and 51% for the β-subunit⁵. These results indicate that an entirely new function which enables species to adapt to a new environment could evolve in a protein by a relatively small number of amino-acid substitutions in key positions⁶.