TRANSPLANTING A UNIQUE ALLOSTERIC EFFECT FROM CROCODILE INTO HUMAN HEMOGLOBIN

CROCODILES are able to remain under water for more than one hour witho ut 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 th eir breath, bicarbonate ions, the final product of respiration, accumu late and drastically reduce the oxygen affinity of haemoglobin, releas ing it large fraction of haemoglobin-bound oxygen into the tissues(3,4 ). We have now located the bicarbonate-ion-binding site at the alpha(1 ) beta(2)-subunit interface by making various human-crocodile chimaeri c haemoglobins. Furthermore, we have been able to transplant the bicar bonate effect into human haemoglobin by replacing only a few residues, even though the amino-acid sequence identity between crocodile (Croco dylus niloticus) and human haemoglobins is only 68% for the alpha- and 51% for the beta-subunit(5). 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 substi tutions in key positions(6).