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LETTER

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

¹Howard Hughes Medical Institute, ²Center for Immunology, and ³McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA

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.]

⁵ Genaissance Pharmaceuticals, Five Science Park, New Haven, Connecticut 06511, USA;

⁶ Egea Biosciences, Inc., 6759 Mesa Ridge Road, Suite 100, San Diego, California 92121, USA

Present addresses:

⁷ Corresponding author.

E-MAIL kfl{at}chop.swmed.edu; FAX (214) 648-5453.

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.975303.

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