A GENE REMNANT IN THE RABBIT MHC RELATED TO HLA-DR-ALPHA

The screening of a rabbit genomic library yielded 2 HLA-DR-alpha-related clones. One of these was previously shown to contain a functional gene (RLA-DR-alpha) closely related to HLA-DR-alpha. The second DR-related clone, designated DF, was mapped to the rabbit MHC class II region by genetic studies. DF contains contiguous sequences that have significant homology to the RLA-DR-alpha transmembrane-coding region (contained in exon 4 of RLA-DR-alpha) and to part of intron 4. These 2 stretches were reversed in DF when compared to other class II genes, and were flanked on both sides by direct repeats of 130 bp with 85% sequence identity. The presence of the transmembrane sequence without the coding sequences that accompany it in DR-alpha, and the observation of the repeats, suggests that the DF region played a role in evolution of class II genes. Genomic blots revealed sequences hybridizing to DF in all rabbits tested and in other lagomorph species. The ratio of replacement to silent substitutions in the DF transmembrane region differed significantly from functional class II genes suggesting an absence of recent selective pressure. An additional direct repeat of the C type, similar to that found in rabbit cytochrome p450, certain class I MHC, TcR-beta and uteroglobin genes, was also present in the DF fragment.