Dijkstra Johannes Martinus, Katagiri Takayuki, Hosomichi Kazuyoshi, Yanagiya Kazuyo, Inoko Hidetoshi, Ototake Mitsuru, Aoki Takashi, Hashimoto Keiichiro, Shiina Takashi
Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
Immunogenetics. 2007 Apr;59(4):305-21. doi: 10.1007/s00251-007-0198-6. Epub 2007 Feb 23.
Most of the previously studied teleost MHC class I molecules can be classified into two broad lineages: "U" and "Z/ZE." However, database reports on genes in cyprinid and salmonid fishes show that there is a third major lineage, which lacks detailed analysis so far. We designated this lineage "L" because of an intriguing linkage characteristic. Namely, one zebrafish L locus is closely linked with MHC class II loci, despite the extensively documented nonlinkage of teleost class I with class II. The L lineage consists of highly variable, nonclassical MHC class I genes, and has no apparent orthologues outside teleost fishes. Characteristics that distinguish the L lineage from most other MHC class I are (1) absence of two otherwise highly conserved tryptophan residues W51 and W60 in the alpha1 domain, (2) a low GC content of the alpha1 and alpha2 exons, and (3) an HINLTL motif including a possible glycosylation site in the alpha3 domain. In rainbow trout (Oncorhynchus mykiss) we analyzed several intact L genes in detail, including their genomic organization and transcription pattern. The gene Onmy-LAA is quite different from the genes Onmy-LBA, Onmy-LCA, Onmy-LDA, and Onmy-LEA, while the latter four are similar and categorized as "Onmy-LBA-like." Whereas the Onmy-LAA gene is organized like a canonical MHC class I gene, the Onmy-LBA-like genes are processed and lack all introns except intron 1. Onmy-LAA is predominantly expressed in the intestine, while the Onmy-LBA-like transcripts display a rather homogeneous tissue distribution. To our knowledge, this is the first description of an MHC class I lineage with multiple copies of processed genes, which are intact and transcribed. The present study significantly improves the knowledge of MHC class I variation in teleosts.
大多数先前研究的硬骨鱼MHC I类分子可分为两个主要谱系：“U”和“Z/ZE”。然而，鲤科和鲑科鱼类基因的数据库报告显示，存在第三个主要谱系，目前缺乏详细分析。由于一个有趣的连锁特征，我们将这个谱系命名为“L”。也就是说，尽管有大量文献记载硬骨鱼I类与II类不连锁，但一条斑马鱼L位点与MHC II类位点紧密连锁。L谱系由高度可变的非经典MHC I类基因组成，在硬骨鱼之外没有明显的直系同源物。将L谱系与大多数其他MHC I类区分开来的特征有：（1）α1结构域中不存在另外两个高度保守的色氨酸残基W51和W60；（2）α1和α2外显子的GC含量低；（3）α3结构域中有一个包括可能糖基化位点的HINLTL基序。在虹鳟（Oncorhynchus mykiss）中，我们详细分析了几个完整的L基因，包括它们的基因组结构和转录模式。Onmy-LAA基因与Onmy-LBA、Onmy-LCA、Onmy-LDA和Onmy-LEA基因有很大不同，而后四个基因相似，归类为“Onmy-LBA样”。Onmy-LAA基因的组织方式类似于典型的MHC I类基因，而Onmy-LBA样基因经过加工，除了内含子1外没有其他内含子。Onmy-LAA主要在肠道中表达，而Onmy-LBA样转录本显示出相当均匀一致的组织分布。据我们所知，这是对具有多个加工基因拷贝且完整并转录的MHC I类谱系的首次描述。本研究显著提高了对硬骨鱼MHC I类变异的认识。
