Evolution of immunoglobulin heavy chain variable region genes: a VH family can last for 150-200 million years or longer.

Many immunoglobulin variable region (IgV) genes are present in the vertebrate genome and provide a basis for antibody diversity. IgV genes have been classified into distinct families according to DNA sequence similarity. Comparisons of VH and VL genes from two mammalian species (mouse and human) have led to the conclusion that some V gene families are stable over 65 million years of evolution. Here we show that a VH family can be stable for 150-200 million years or longer. This conclusion is drawn from our extensive comparison of VH genes between two species of low vertebrates (rainbow trout and catfish), and from the estimation of species divergence time by the substitution rate of an IgM constant domain. The estimated speed of VH gene evolution explains the moderate degree of sequence similarity in VH gene families between a mammal (mouse) and a teleost (rainbow trout). The distribution of species-specific amino acid residues in certain VH families indicates that the process of sequence homogenization plays a major role in shaping the V gene family.