Sequence Relationships among the Variable Regions of Immunoglobulin Heavy Chains from Various Mammalian Species

Immunoglobulin heavy chains of myeloma proteins from dogs and cata have been subjected to automated sequence analysis. When the results were compared with human heavy-chain sequences, all the dog and cat proteins could be unequivocally assigned to the V_HIII subgroup. This pattern contrasts with that in human proteins in which only 25% of all heavy chains sequenced belong to this subgroup. The 30 residues at the NH₂ termini of dog, cat, and human heavy chains had sequence identities near or exceeding 90%, in contrast to established interspecies sequence homologies of constant regions of about 60%. Some genes of the immunoglobulin heavy-chain variable region thus appear to have been conserved through a considerable period of evolutionary time. The analyses also showed that the presence of certain amino acids at certain positions in these heavy chains could be correlated with the species of origin. The occurrence of such "phylogenetically associated" residues is most consistent with the presence of a restricted number of genes in the heavy-chain variable region pool.