What is the structural difference between beta and gamma globin chains of Hb? Hemoglobins are tetramers composed of pairs of two different polypeptide subunits. The subunit composition of the principal hemoglobins are α2β2 (HbA; normal adult hemoglobin), α2γ2 (HbF; fetal hemoglobin) and α2δ2 (HbA2; a minor adult hemoglobin) The total number of amino acids in beta chain and gamma chain is the same-146. The higher affinity of HbF to oxygen is due to presence of serine(in gamma chain) in place of histidine(in beta chain), which inhibits its binding with 2,3-bisphosphoglyceric acid. Is this the only difference, or are there more such differences in the amino acid sequence?

Here's a pairwise sequence alignment of the human hemoglobin beta (HBB) and gamma (HBG1) chains:


HBB_HUMAN 1 VHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLST 50
.|.|.|:|:.:|:|||||||::.|||.|||||||||||||||:|||:||:
HBG1_HUMAN 1 GHFTEEDKATITSLWGKVNVEDAGGETLGRLLVVYPWTQRFFDSFGNLSS 50

HBB_HUMAN 51 PDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDP 100
..|:||||||||||||||.:..|.:.|||:||||||.|||||||||||||
HBG1_HUMAN 51 ASAIMGNPKVKAHGKKVLTSLGDAIKHLDDLKGTFAQLSELHCDKLHVDP 100

HBB_HUMAN 101 ENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH 146
|||:|||||||.|||.||||||||.|||::||:|..||:||:.:||
HBG1_HUMAN 101 ENFKLLGNVLVTVLAIHFGKEFTPEVQASWQKMVTAVASALSSRYH 146


You can see the H143S (or S143H?) substitution, as well as many more.