Hemoglobin function in the vertebrates: an evolutionary model

Area of Science:

• Biochemistry
• Evolutionary Biology
• Physiology

Background:

• Hemoglobin's quaternary structure, cooperativity, Bohr effect, and organic phosphate regulation vary across vertebrates.
• Understanding hemoglobin's functional evolution provides insights into vertebrate adaptation.

Purpose of the Study:

• To deduce a phylogeny of hemoglobin function in vertebrates.
• To propose evolutionary pathways for hemoglobin structure and function.

Main Methods:

• Comparative analysis of existing data on vertebrate hemoglobins.
• Phylogenetic reconstruction based on functional characteristics.

Main Results:

• A proposed evolutionary path from monomeric to dimeric (e.g., lamprey) and finally tetrameric hemoglobin.
• Early tetrameric hemoglobins likely dissociated into dimers upon oxygenation.
• Organic phosphate binding sites evolved early, with ATP as the initial regulator, later switching to DPG and IP5.

Conclusions:

• Hemoglobin's functional complexity evolved through a series of amino acid substitutions and gene duplications.
• Changes in red blood cell metabolism influenced the evolution of hemoglobin's allosteric effectors.
• The shift from ATP to DPG/IP5 regulation reflects adaptation to varying metabolic conditions in vertebrates.