Unlike all other mammalian species, which have only one class I region, rat and mouse possess a second class I region on the centromeric side of the MHC. The mouse has class Ia genes in both the centromeric H2-K and the telomeric H2-D region, whereas the rat has class Ia genes only in the centromeric RT1.A region. Bat1 is the last gene of the class III region in the mouse, and H2-D was mapped 10 kb telomeric of Bat1. To determine whether the rat possesses an H2-D orthologue, we sequenced a cosmid clone that contains rat Bat1 and an adjacent class I gene, RT1.46l. Homology searches suggest a transition in the rat sequence with a proximal stretch containing Nfkbil1, ATP6G, and Bat1, which is homologous to the mouse H2-D region, and a more-distal stretch, which contains the class I gene and has many similarities to mouse H2-Q region sequences. Downstream of Bat1 is a sequence stretch with great similarity to intron 3 of H2-D, which is not present in any of the rat class I genes but is found in mouse H2-K, D-, and -Q region genes. Numerous repetitive elements indicate that the region is prone to repeat-mediated rearrangements. A putative H2-D orthologue may have been present at this location and lost by genomic rearrangements, leaving the short intronic sequence behind. The class I gene RT1.46l has an open reading frame, but it is unlike H2-D due to a unique 5′UTR shared with H2-Q1 and Q2, the absence of the B2 SINE repeat characteristic of H2-D/L, and the apparent lack of surface expression. We conclude that at least the LEW rat (RT1l) does not possess an H2-D orthologue.
- Bat1 microsatellite
- Interspecies comparison
- MHC class I genes
- Major histocompatibility complex
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