Fifty-million-year-old polymorphism at an immunoglobulin variable region gene locus in the rabbit evolutionary lineage

摘要

The Ig heavy chain variable region (V_H) genes encode the antigen-binding regions of antibodies. The rabbit genome contains more than 100 V_H genes, but only one (V_H1) is preferentially used in the VDJ gene rearrangement. Three highly divergent alleles occur at this V_H1 locus in most rabbit populations. These three V_H alleles are also present in snowshoe hare populations, indicating that the polymorphism of the V_H1 alleles is trans-specific. Here we report the results of a phylogenetic analysis of rabbit Ig germ-line V_H genes (alleles) together with V_H genes from humans and mice. We have found that all rabbit V_H genes belong to one mammalian V_H group (group C), which also includes various human and mouse V_H genes. Using the rate of nucleotide substitution obtained from human and mouse V_H sequences, we have estimated that the V_H1 polymorphism in the rabbit lineage has been maintained for about 50 million years. This extremely long persistence of V_H1 polymorphism is apparently caused by overdominant selection, though the real mechanism is un- clear.