Organization and evolution of immunoglobulin V(H) gene subgroups

The organization and evolution of immunoglobulin variable region genes was studied by comparing human and mouse heavy chain variable region (V(H)) genes. We show that a V(H) gene subgroup constitutes a physically linked multigene family separated from another V(H) subgroup. We mapped the V(H)III gene subgroup to be 3' to the V(H)II gene subgroup based on deletion of V(H) genes after V-D-J rearrangement. The results indicate that the human V(H)III gene subgroup underwent a significant gene expansion as compared to the mouse V(H)III subgroup. Amino acid sequence data indicate that human V(H)III genes correspond to only a small subset of mouse V(H)III genes. Human V(H)III contain a shorter intron and are two codons shorter than most BALB/c mouse V(H)III genes. The nature of nucleotide substitutions between V(H) genes within a species (human) is similar to that between genes of different species (human/mouse). Both contain approximately 50% silent substitutions.