Unprecedented intraspecific diversity of the MHC class I region of a teleost medaka, Oryzias latipes.

The major histocompatibility complex (MHC) is present at a single chromosomal locus of all jawed vertebrate analyzed so far, from sharks to mammals, except for teleosts whose orthologs of the mammalian MHC-encoded genes are dispersed at several chromosomal loci. Even in teleosts, several class IA genes and those genes directly involved in class I antigen presentation preserve their linkage, defining the teleost MHC class I region. We determined the complete nucleotide sequence of the MHC class I region of the inbred HNI strain of medaka, Oryzias latipes (northern Japan population-derived), from four overlapping bacterial artificial chromosome (BAC) clones spanning 540,982 bp, and compared it with the published sequence of the corresponding region of the inbred Hd-rR strain of medaka (425,935 bp, southern Japan population-derived) as the first extensive study of intraspecies polymorphisms of the ectotherm MHC regions. A segment of about 100 kb in the middle of the compared sequences encompassing two class Ia genes and two immunoproteasome subunit genes, PSMB8 and PSMB10, was so divergent between these two inbred strains that a reliable sequence alignment could not be made. The rest of the compared region (about 320 kb) showed a fair correspondence, and an approximately 96% nucleotide identity was observed upon gap-free segmental alignment. These results indicate that the medaka MHC class I region contains an approximately 100-kb polymorphic core, which is most probably evolving adaptively by accumulation of point mutations and extensive genetic rearrangements such as insertions, deletions, and duplications.

Repetitive elements in the major histocompatibility complex (MHC) class I region of a teleost, medaka: identification of novel transposable elements.

The repetitive elements of medaka (Oryzias latipes) are poorly characterized in spite of recent rapid progress in the medaka genome analysis. Here we report the characterization of the repetitive elements in the major histocompatibility complex (MHC) class I region, which spans about 400 kb and is one of the best characterized regions of the medaka genome. Microsatellite, low complexity regions, transposable elements, and other repeats occupied 0.68, 0.98, 7.0 and 2.9%, respectively, of the MHC class I region. Eleven transposable elements, three LTR-type, six LINE-type and two DNA-type, including several novel ones, were identified. Genomic Southern hybridization analysis indicated that these LINE-type and DNA-type elements have many copies in the medaka genome, whereas the LTR-type elements have only several copies. The comparison of the medaka MHC class I region with those of zebrafish and fugu shows the presence of three medaka lineage-specific tandem duplications of the PSMB (proteasome beta-type subunit) 8 and class Ia genes. Since eight of the 11 transposable elements were located in this region, these elements may have played a role in the medaka-specific DNA rearrangement.

Nucleotide sequence of the MHC class I genomic region of a teleost, the medaka (Oryzias latipes).

Teleost orthologs of the human major histocompatibility complex (MHC)-encoded genes show a dispersed distribution over several chromosomal loci. However, some of them, including the MHC class I alpha chain genes, are tightly linked to each other, forming the teleost MHC class I region. To elucidate the evolution of vertebrate MHC, we have determined the complete nucleotide sequences of two bacterial artificial chromosome (BAC) clones, encompassing the MHC class I region of the inbred Hd-rR strain of the medaka (Oryzias latipes). The 425862 bp nucleotide sequence predicted 20 possibly expressed genes and three pseudogenes. Except for one gene, CIZ, whose human ortholog is located at 12p13.31, all identified genes were orthologs or closely related relatives of the human MHC-encoded genes. Two classical class I alpha chain genes and the six other genes directly involved in class I antigen presentation formed an uninterrupted cluster. Comparison of the MHC class I region genes among three teleost species, the medaka, zebrafish and pufferfish, indicated that the content, but not the order or transcriptional orientation, of the genes is highly conserved. These results suggest that a strong selective pressure has conserved the linkage of certain MHC genes during vertebrate evolution, despite recurrent genetic rearrangements.