Hemoglobin function in the vertebrates: an evolutionary model.
Comparative data on quaternary structure, cooperativity, Bohr effect and regulation by organic phosphates are reviewed for vertebrate hemoglobins. A phylogeny of hemoglobin function in the vertebrates is deduced. It is proposed that from the monomeric hemoglobin of the common ancestor of vertebrates, a deoxy dimer, as seen in the lamprey, could have originated with a single amino acid substitution. The deoxy dimer has a Bohr effect, cooperativity and a reduced oxygen affinity compared to the monomer. One, or two, additional amino acid substitutions could have resulted in the origin of a tetrameric deoxy hemoglobin which dissociated to dimers on oxygenation. Gene duplication, giving incipient alpha and beta genes, probably preceded the origin of a tetrameric oxyhemoglobin. The origin of an organic phosphate binding site on the tetrameric hemoglobin of an early fish required only one, or two, amino acid substitutions. ATP was the first organic phosphate regulator of hemoglobin function. The binding of ATP by hemoglobin may have caused the original elevation in the concentration of ATP in the red blood cells by relieving end product inhibition of ATP synthesis. The switch from regulation of hemoglobin function by ATP to regulation by DPG may have been a consequence of the curtailment of oxidative phosphorylation in the red blood cell. The basic mechanisms by which ATP and DPG concentrations can respond to strss on the oxygen transport system were present before the origin of an organic phosphate binding site on hemoglobin. A switch from ATP regulation to IP5 regulation occurred in the common ancestor of birds.
D000255:Adenosine Triphosphate / Q000097:blood / Q000378:metabolism; D000663:Amphibians; D000818:Animals; D005075:Biological Evolution; D001717:Birds; D002645:Chickens; D004163:Diphosphoglyceric Acids / Q000097:blood / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005399:Fishes; D005796:Genes; D006160:Guanosine Triphosphate / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007294:Inositol / Q000378:metabolism; D008322:Mammals; D008954:Models, Biological; D009154:Mutation; D009943:Organophosphorus Compounds / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010802:Phylogeny; D010833:Phytic Acid / Q000378:metabolism; D011487:Protein Conformation; D012104:Reptiles; D013045:Species Specificity; D014508:Urea / Q000494:pharmacology; D014714:Vertebrates / Q000097:blood*
D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D009943:Organophosphorus Compounds; D007294:Inositol; D010833:Phytic Acid; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D014508:Urea; D010100:Oxygen