Abstract
Three sequence lineages of MHC class I genes have been described in zebrafish (Danio rerio): U, Z, and L. The U lineage genes encoded on zebrafish chromosome 19 are predicted to provide the classical function of antigen presentation. This MHC class I locus displays significant haplotypic variation and is the only MHC class I locus in zebrafish that shares conserved synteny with the core mammalian MHC. Here, we describe two MHC class I U lineage genes, mhc1ula and mhc1uma, that map to chromosome 22. Unlike the U lineage proteins encoded on chromosome 19, Ula and Uma likely play a nonclassical role as they lack conservation of key peptide binding residues, display limited polymorphic variation, and exhibit tissue-specific expression. We also describe a null haplotype at this chromosome 22 locus in which the mhc1ula and mhc1uma genes are absent due to a ~30 kb deletion with no other MHC class I sequences present. Functional and non-functional transcripts of mhc1ula and mhc1uma were identified; however, mhc1uma transcripts were often not amplified or amplified at low levels from individuals possessing an apparently bona fide gene. These distinct U lineage genes may be restricted to the superorder Ostariophysi as similar sequences only could be identified from the blind cavefish (Astyanax mexicanus), fathead minnow (Pimephales promelas), goldfish (Carassius auratus), and grass carp (Ctenopharyngodon idella).
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Acknowledgments
We thank John Rawls (Duke University), John Godwin (NC State University), and Sergei Revskoy (University of Illinois at Chicago) for sharing zebrafish lines, Sean McConnell (University of Chicago) for helpful discussions regarding MHC class I nomenclature, Ivan Rodriguez-Nunez for dissecting tissues for RNA-Seq, Jennifer Schaff, Cory Dashiell, and Julie Macialek for assistance with RNA-Seq, and Betsy Scholl and Dustin Wcisel for bioinformatics support. H.D. is supported in part by a National Institutes of Health Biotechnology Traineeship (T32 GM008776) and by a Joseph E. Pogue Fellowship through the UNC Royster Society of Fellows.
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Dirscherl, H., Yoder, J.A. A nonclassical MHC class I U lineage locus in zebrafish with a null haplotypic variant. Immunogenetics 67, 501–513 (2015). https://doi.org/10.1007/s00251-015-0862-1
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DOI: https://doi.org/10.1007/s00251-015-0862-1