Co-duplication of olfactory receptor and MHC class I genes in the mouse major histocompatibility complex.

We report the 897 kb sequence of a cluster of olfactory receptor (OR) genes located at the distal end of the major histocompatibility complex (MHC) class I region on mouse chromosome 17 of strain 129/SvJ (H2bc). With additional information from the mouse genome draft sequence, we identified 59 OR loci (approximately 20% pseudogenes) in contrast to only 25 OR loci (approximately 50% pseudogenes) in the corresponding centromeric OR cluster that is part of the 'extended MHC class I region' on human chromosome 6. Comparative analysis leads to three major observations: (i) most of the OR subfamilies have evolved independently in the two species, expanding more in the mouse, and resulting in co-orthologs--subfamilies of highly similar paralogs that keep orthologous relationships with their human counterparts; (ii) three of the mouse OR subfamilies have no orthologs in humans; and (iii) MHC class I loci are interspersed in the OR cluster in mouse but not in human, and were subjected to co-duplication with OR genes. Screening of our sequence against the available sequences of other strains/haplotypes revealed that most of the OR loci are polymorphic and that the number of OR loci may vary among strains/haplotypes. Our findings that MHC-linked OR loci share duplication with MHC class I loci, have duplicated extensively and are polymorphic revives questions about potential reciprocal influences acting on the dynamics and evolution of the H2 region and the H2-linked OR loci.

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