Positive Darwinian Selection Observed at the Variable-region Genes of Immunoglobulins

To examine Gojobori and Nei's hypothesis that the immunoglobulin heavy-chain variable-region (VH) genes in mammals are subject to diversity-enhancing selection, we studied the rates of synonymous and nonsynonymous nucleotide substitution in the complementarity-determining regions (CDRs) and in the framework regions (FRs) of mouse and human VH genes. The results obtained indicate that the non-synonymous rate is higher than the synonymous rate in CDRs, whereas the reverse is true in FRs. This observation supports Gojobori and Nei's hypothesis and suggests that diversity-enhancing selection (similar to overdominant selection) operates mainly in CDRs and that this is one of the evolutionary factors that increase antibody diversity.