title: Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution.
abstract: Antigen processing and presentation genes found within the MHC are among the most highly polymorphic genes of vertebrate genomes, providing populations with diverse immune responses to a wide array of pathogens. Here, we describe transcriptome, exome, and whole-genome sequencing of clonal zebrafish, uncovering the most extensive diversity within the antigen processing and presentation genes of any species yet examined. Our CG2 clonal zebrafish assembly provides genomic context within a remarkably divergent haplotype of the core MHC region on chromosome 19 for six expressed genes not found in the zebrafish reference genome: mhc1uga, proteasome-β 9b (psmb9b), psmb8f, and previously unknown genes psmb13b, tap2d, and tap2e We identify ancient lineages for Psmb13 within a proteasome branch previously thought to be monomorphic and provide evidence of substantial lineage diversity within each of three major trifurcations of catalytic-type proteasome subunits in vertebrates: Psmb5/Psmb8/Psmb11, Psmb6/Psmb9/Psmb12, and Psmb7/Psmb10/Psmb13. Strikingly, nearby tap2 and MHC class I genes also retain ancient sequence lineages, indicating that alternative lineages may have been preserved throughout the entire MHC pathway since early diversification of the adaptive immune system ∼500 Mya. Furthermore, polymorphisms within the three MHC pathway steps (antigen cleavage, transport, and presentation) are each predicted to alter peptide specificity. Lastly, comparative analysis shows that antigen processing gene diversity is far more extensive than previously realized (with ancient coelacanth psmb8 lineages, shark psmb13, and tap2t and psmb10 outside the teleost MHC), implying distinct immune functions and conserved roles in shaping MHC pathway evolution throughout vertebrates.
authors: Section of Hematology-Oncology and Stem Cell Transplant, Department of Pediatrics, The University of Chicago, Chicago, IL 60637; scmcconnell@uchicago.edu jdejong@peds.bsd.uchicago.edu.
authors: Sean C
authors: SC
authors: McConnell
authors: Center for Research Informatics, The University of Chicago, Chicago, IL 60637;
authors: Kyle M
authors: KM
authors: Hernandez
authors: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607; Genomic Sciences Graduate Program, North Carolina State University, Raleigh, NC 27607;
authors: Dustin J
authors: DJ
authors: Wcisel
authors: Vertebrate Development and Genetics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
authors: Ross N
authors: RN
authors: Kettleborough
authors: Vertebrate Development and Genetics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom;
authors: Derek L
authors: DL
authors: Stemple
authors: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607; Genomic Sciences Graduate Program, North Carolina State University, Raleigh, NC 27607; Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27607.
authors: Jeffrey A
authors: 0000-0002-6083-1311
authors: JA
authors: Yoder
authors: Center for Research Informatics, The University of Chicago, Chicago, IL 60637;
authors: Jorge
authors: J
authors: Andrade
authors: Section of Hematology-Oncology and Stem Cell Transplant, Department of Pediatrics, The University of Chicago, Chicago, IL 60637; scmcconnell@uchicago.edu jdejong@peds.bsd.uchicago.edu.
authors: Jill L O
authors: JL
authors: de Jong
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D005075:Biological Evolution; D019976:Cloning, Organism; D003546:Cysteine Endopeptidases / Q000145:classification / Q000235:genetics* / Q000276:immunology; D016678:Genome; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D015395:Histocompatibility Antigens Class I / Q000145:classification / Q000235:genetics* / Q000276:immunology; D010802:Phylogeny; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000145:classification / Q000235:genetics / Q000276:immunology; D059467:Transcriptome; D015027:Zebrafish / Q000145:classification / Q000235:genetics* / Q000276:immunology; D029961:Zebrafish Proteins / Q000145:classification / Q000235:genetics* / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D020033:Protein Isoforms; D029961:Zebrafish Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C121055:Psmb7 protein, zebrafish
keywords: CG2 clonal zebrafish; MHC class I pathway; comparative genomics; major histocompatibility; proteasome and TAP evolution