Structural conservation of hypervariable regions in immunoglobulins evolution.

Analysis of human and mouse immunoglobulins has shown that five of six hypervariable regions that form the antigen binding site have a small repertoire of main chain conformations (canonical structures). Cartilaginous fishes are the most distantly related species to humans known to have an immune system, their evolutionary lines having diverged 450 million years ago. An analysis of VH and V kappa sequences from these fishes shows that all the main chain structures in their L1, L2, H1 and H2 hypervariable regions, and one of those in the L3 region, are the same as those most commonly found in human and mouse. This implies that the canonical structures occurring most commonly in hypervariable regions arose very early in the stages of the evolution of the immune system.