Phylogenetically associated residues within the VH3 subgroup of several mammalian species. Evidence for a "pauci-gene" basis for antibody diversity.
Immunoglobulin heavy chains from IgG pools of several mammalian species have been subjected to Edman degradation on an automated protein sequencer. The percentage of unblocked vs. blocked heavy chains was estimated from the yield of the invariant valine in the second position. Further analysis of these unblocked polypeptides unequivocally placed them in the V(HIII) subgroup on the basis of homology with known human heavy chain sequences. The mammals studied could be divided into three distinct categories on the basis of the distribution of the V(HIII) subgroup. In several species the V(HIII) subgroup could not be detected while, in others, virtually all of the heavy chains belonged to this subgroup. Several species had intermediate amounts with the level of the V(HIII) subgroup restricted to between 19 and 29% of the total pool. Within experimental error, all members of a given order had a similar V(HIII) subgroup distribution. Further amino acid sequence studies illustrated a high degree of structural homogeneity in the heavy chains of IgG isolated from pooled sera of a number of mammalian species. The very close amino acid sequence homologies of the amino terminal 24 residues of the various pools corroborated conclusions previously obtained using several myeloma proteins from some of these same species. In particular, certain phylogenetically associated residues were identifiable at characteristic positions in the pools in confirmation of their identification in the myeloma proteins. The simplest assumptions would suggest that these findings are more compatible with a pauci-gene than a multi-gene basis for the generation of antibody diversity.
D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats; D002417:Cattle; D004285:Dogs; D005796:Genes; D006041:Goats; D006168:Guinea Pigs; D000882:Haplorhini; D007128:Immunoglobulin Fragments / Q000032:analysis*; D007074:Immunoglobulin G / Q000032:analysis; D051379:Mice; D008954:Models, Biological; D011817:Rabbits; D051381:Rats; D012756:Sheep; D013045:Species Specificity; D013552:Swine; D014633:Valine / Q000032:analysis
D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D014633:Valine