Abstract
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 α1 domain, (2) a low GC content of the α1 and α2 exons, and (3) an HINLTL motif including a possible glycosylation site in the α3 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.
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Acknowledgements
The study was supported by “the promotion of basic research activities for innovative biosciences” funded by Bio-oriented Technology Research Advancement Institution, Japan, and by KAKENHI (Grant-in-Aid for Scientific Research) on Priority Areas “Comparative Genomics” from the Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank Attila Kumánovics, University of Utah, for careful reading of the manuscript.
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Supplementary Fig. 1
Alignment of Onmy-L nucleotide sequences. The depicted Onmy-LAA*0101 sequence is a combination of the 5′RACE cDNA (without intron) and genomic intron 1, the latter added to the figure to allow comparison with the Onmy-LBA-like genes. For Onmy-LBA*0101, Onmy-LCA*0101, Onmy-LDA*0101 and Onmy-LEA*0101 genomic sequences are shown; the depicted Onmy-LCA sequence is an assembly of the full-length Onmy-LCA genomic fragment and its upstream region derived from the Onmy-LEA+Onmy-LCA sequence. LCAtr: For Onmy-LCA*0101 this transcription start point was determined. The depicted Onmy-LDA*0101 fragment (part of the BAC clone) includes sequences upstream of the open reading frame for comparison with Onmy-LCA*0101. The fragment Onmy-LDA*0102 (not shown) was amplified with primers pLDA-L-F1 and pLDA-α2-R1 and differs from the corresponding Onmy-LDA*0101 fragment by having G460 replaced by a T. Amino acids encoded by Onmy-LAA*0101 are shown above the middle nucleotides of codons. Primer sequences used for RT-PCR analysis are underlined and indicated under the alignment. Dashes indicate gaps, asterisks indicate nucleotides that are shared between all the sequences compared in that region, and dots indicate positions that are shared in most of the compared sequences. Stop codons are boxed. Intron positions of Onmy-LAA*0101 correspond to the α1, α2 and α3 borders or are indicated by arrowheads. TM/CY, transmembrane/cytoplasmic region. In addition to point mutations, gene conversion events presumably also contributed to the variation in this gene family: Namely, whereas the α2 regions of Onmy-LBA, Onmy-LCA and Onmy-LDA have comparable similarity indices (80–84% nt identity), the α1 regions of Onmy-LBA and Onmy-LCA are nearly identical (99% nt identity) but different from Onmy-LDA-α1 (83–84% identity) (DOC 49 kb)
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Dijkstra, J.M., Katagiri, T., Hosomichi, K. et al. A third broad lineage of major histocompatibility complex (MHC) class I in teleost fish; MHC class II linkage and processed genes. Immunogenetics 59, 305–321 (2007). https://doi.org/10.1007/s00251-007-0198-6
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DOI: https://doi.org/10.1007/s00251-007-0198-6