Species adaptation in a protein molecule.

Area of Science:

• Biochemistry and Molecular Evolution
• Comparative Physiology

Background:

• Hemoglobin's allosteric properties, particularly responses to non-oxygen ligands, show significant variation across vertebrate species.
• Understanding human hemoglobin's cooperative effects provides a basis for exploring these interspecies differences.

Purpose of the Study:

• To investigate the stereochemical underpinnings of varying hemoglobin allosteric responses in vertebrates.
• To correlate amino acid sequence changes with functional adaptations in hemoglobin.

Main Methods:

• Comparative analysis of hemoglobin amino acid sequences across vertebrate classes.
• Inference of structural and functional implications based on known human hemoglobin stereochemistry.

Main Results:

• Vertebrate hemoglobin tertiary and quaternary structures are highly conserved.
• Most interspecies amino acid substitutions are functionally neutral.
• Novel ligand responses evolved through minimal amino acid changes (1-5) at critical sites.
• Superfluous allosteric responses can be inactivated by various substitutions, not just reversals.

Conclusions:

• Hemoglobin's core structure is evolutionarily stable.
• Functional adaptations in hemoglobin allostery arise from limited, targeted amino acid substitutions.
• Inactivation of vestigial allosteric functions is a flexible evolutionary process.