Species-Specific Class I Gene Expansions Formed the Telomeric 1 Mb of the Mouse Major Histocompatibility Complex

Abstract

We have determined the complete sequence of 951,695 bp from the class I region of H2, the mouse major histocompatibility complex ( Mhc ) from strain 129/Sv (haplotype bc ). The sequence contains 26 genes. The sequence spans from the last 50 kb of the H2-T region, including 2 class I genes and 3 class I pesudogenes, and includes the H2-M region up to Gabbr1. A 500-kb stretch of the H2-M region contains 9 class I genes and 4 pseudogenes, which fall into two subfamilies, M1 and M10 , distinct from other mouse class I genes. This M1/M10 class I gene-cluster is separated from the centromeric H2-T and the telomeric H2-M4, - 5 and -6 class I genes by “nonclass I genes”. Comparison with the corresponding 853-kb region of the human Mhc, which includes the HLA-A region, shows a mosaic of conserved regions of orthologous nonclass I genes separated by regions of species-specific expansion of paralogous Mhc class I genes. The analysis of this mosaic structure illuminates the dynamic evolution of the Mhc class I region among mammals and provides evidence for the framework hypothesis. [Supplemental material is available online at www.genome.org . The sequence data from this study have been submitted to GenBank under accession nos. AC005413 , AC005665 , AF532111 – AF532117 . A preliminary draft sequence was earlier submitted as AC002615 and replaced this year by NT002615.]