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The Journal of Immunology, 2006, 176: 3674-3685.
Copyright © 2006 by The American Association of Immunologists

Ancestral Organization of the MHC Revealed in the Amphibian Xenopus1

Yuko Ohta2,*, Wilfried Goetz*, M. Zulfiquer Hossain*, Masaru Nonaka{dagger} and Martin F. Flajnik*

* University of Maryland, Department of Microbiology and Immunology, 655 West Baltimore Street, BRB13-009, Baltimore, MD 21201; and {dagger} Department of Biological Sciences, Graduate School of Science, University ofTokyo, Hongo, Bunkyo-ku, Tokyo, Japan

With the advent of the Xenopus tropicalis genome project, we analyzed scaffolds containing MHC genes. On eight scaffolds encompassing 3.65 Mbp, 122 MHC genes were found of which 110 genes were annotated. Expressed sequence tag database screening showed that most of these genes are expressed. In the extended class II and class III regions the genomic organization, excluding several block inversions, is remarkably similar to that of the human MHC. Genes in the human extended class I region are also well conserved in Xenopus, excluding the class I genes themselves. As expected from previous work on the Xenopus MHC, the single classical class I gene is tightly linked to immunoproteasome and transporter genes, defining the true class I region, present in all nonmammalian jawed vertebrates studied to date. Surprisingly, the immunoproteasome gene PSMB10 is found in the class III region rather than in the class I region, likely reflecting the ancestral condition. Xenopus DM{alpha}, DMbeta, and C2 genes were identified, which are not present or not clearly identifiable in the genomes of any teleosts. Of great interest are novel V-type Ig superfamily (Igsf) genes in the class III region, some of which have inhibitory motifs (ITIM) in their cytoplasmic domains. Our analysis indicates that the vertebrate MHC experienced a vigorous rearrangement in the bony fish and bird lineages, and a translocation and expansion of the class I genes in the mammalian lineage. Thus, the amphibian MHC is the most evolutionary conserved MHC so far analyzed.




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