Tracing the evolution of H-2 D region genes using sequences associated with a repetitive element

The class I genes in the murine MHC are genetically divided into the K, D, Qa, and T1a region subfamilies. These genes presumably arose by duplication from a common class I ancestor. Oligonucleotide probes specific for sequences associated with a moderately repetitive B2 SINE element, which is inserted into the 3' untranslated region of the H-2D and H-2L genes, were used to examine the evolutionary relationship between these classically defined D region genes (H-2D and H-2L) and the other members of the class I gene family. Hybridization analyses of recombinant cosmid and genomic DNA indicated that the D region genes separated genetically from the other members of the class I gene family 12 to 14 million years ago. The evidence suggests that during this time frame the chromosomal segment harboring the characteristic insertion became fixed in the ancestral population which gave rise to Mus domesticus. Previous studies have shown that the number of genes present in the Qa and T1a regions varies among inbred strains and among laboratory stocks of wild mice derived from more distant species on the genus Mus. No evidence was found in this study to support the hypothesis that variation in class I gene number is the result of recent duplications of the functionally defined class I genes of the D region, H-2D and H-2L.