There are more than 300 variants of human hemoglobin gene. Among these only a few are fatal. Hence, the most impoant factor to be conserved in a protein for its function is the:

B i.e. Ligand binding residues Function in biochemistry revolves around a reversible protein ligand interaction.A molecule bound reversibly by a protein is called a 'Ligand'. A ligand binds at a site on the protein called the 'binding site', which is complementary to ligand in size, charge and hydrophobic or hydrophillic character. As long as the ligand binding residues are preserved to allow interaction between the ligand and the binding sites the function will essentially be preserved.Amino acid sequence alterations are compatible will 0 functionally normal haemoglobin: (Acceptable missense mutations) eg. Haemoglobin Hikari has been found in at least two families of Japanese people. This haemoglobin has asparginine substituted for lysine at position 61 in IL 13 chain. (change in AA sequence). This replacement of specific lysine with arginine apparently does not alter the normal function of the 3 chain in these individuals.As long as the domains/ Ligand receptors are preserved, a variation in structure is still compatible with normal function.Environmental changes do not explain why only a few out of 300 variants of human globin gene are incompatible will function.