Diversity of germ-line immunoglobulin VH genes

The sequences of four embryonic mouse immunoglobulin VH genes have been compared. All genes end at codon 98 and code for a hydrophobic signal peptide of 19 residues interrupted at codon -4 by an intron of 83 base pairs. Substitutions occur in all gene segments but at a significantly higher frequency in the hypervariable regions. The data suggest an evolutionary basis for the diversity of immunoglobulin genes. Divergence resulted also in a termination codon in two of the genes, suggesting that part of the V gene repertoire cannot be expressed unless some correction mechanism is available.