Dynamic gene interactions in the evolution of rabbit VH genes: a four codon duplication and block homologies provide evidence for intergenic exchange.

Two rabbit VHa-negative genes, RVH831 and RVH832, were isolated from a single genomic fragment selected by hybridization with the mouse VHIII gene S107V1. RVH831 is a pseudogene with a frameshift mutation in FR3 and a 19 bp deletion within the VH-D splice site. In contrast, RVH832 has an open reading frame and an intact VH-D splice site and thus may be functional. However, RVH832 displays a unique 4 codon duplication/insertion in FR1 that may be the result of an unequal exchange event between two ancestral VH genes. Sequence comparisons between these and other rabbit VH genes reveal patterns of shared blocks of nucleotide substitutions, suggestive of gene conversion. A high overall homology (greater than or equal to 73%) between the compared VH nucleotide sequences suggests that rabbit VH genes may not be organized in clearly divergent families or subgroups.