{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:04:03Z","timestamp":1787504643511,"version":"build-2736575974"},"reference-count":92,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Comparative analyses suggest that the MHC was derived from a prevertebrate \u201cprimordial immune complex\u201d (PIC). PIC duplicated twice in the well-studied two rounds of genome-wide duplications (2R) early in vertebrate evolution, generating four MHC paralogous regions (predominantly on human chromosomes [chr] 1, 6, 9, 19). Examining chiefly the amphibian Xenopus laevis, but also other vertebrates, we identified their MHC paralogues and mapped MHC class I, AgR, and \u201cframework\u201d genes. Most class I genes mapped to MHC paralogues, but a cluster of Xenopus MHC class Ib genes (xnc), which previously was mapped outside of the MHC paralogues, was surrounded by genes syntenic to mammalian CD1 genes, a region previously proposed as an MHC paralogue on human chr 1. Thus, this gene block is instead the result of a translocation that we call the translocated part of the MHC paralogous region (MHCtrans). Analyses of Xenopus class I genes, as well as MHCtrans, suggest that class I arose at 1R on the chr 6\/19 ancestor. Of great interest are nonrearranging AgR-like genes mapping to three MHC paralogues; thus, PIC clearly contained several AgR precursor loci, predating MHC class I\/II. However, all rearranging AgR genes were found on paralogues derived from the chr 19 precursor, suggesting that invasion of a variable (V) exon by the RAG transposon occurred after 2R. We propose models for the evolutionary history of MHC\/TCR\/Ig and speculate on the dichotomy between the jawless (lamprey and hagfish) and jawed vertebrate adaptive immune systems, as we found genes related to variable lymphocyte receptors also map to MHC paralogues.<\/jats:p>","DOI":"10.4049\/jimmunol.1900597","type":"journal-article","created":{"date-parts":[[2019,9,6]],"date-time":"2019-09-06T16:45:18Z","timestamp":1567788318000},"page":"1882-1896","source":"Crossref","is-referenced-by-count":37,"title":["Inferring the \u201cPrimordial Immune Complex\u201d: Origins of MHC Class I and Antigen Receptors Revealed by Comparative Genomics"],"prefix":"10.1093","volume":"203","author":[{"given":"Yuko","family":"Ohta","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Sapporo 060-8638 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0276-1896","authenticated-orcid":false,"given":"Timothy D","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine , Baltimore, MD, 21201"},{"name":"Program in Personalized and Genomic Medicine, University of Maryland School of Medicine , Baltimore, MD, 21201"},{"name":"Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine , Baltimore, MD, 21201"},{"name":"Department of Medicine, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin F","family":"Flajnik","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,10,1]]},"reference":[{"key":"2025030417542647800_r1","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-642-86659-3","volume-title":"Evolution by Gene Duplication.","author":"Ohno","year":"1970"},{"key":"2025030417542647800_r2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/geno.1993.1133","article-title":"Evolution of the vertebrate genome as reflected in paralogous chromosomal regions in man and the house mouse","volume":"16","author":"Lundin","year":"1993","journal-title":"Genomics"},{"key":"2025030417542647800_r3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1601-5223.1997.t01-1-00059.x","article-title":"New insights into the genomic organization and origin of the major histocompatibility complex: role of chromosomal (genome) duplication in the emergence of the adaptive immune system","volume":"127","author":"Kasahara","year":"1997","journal-title":"Hereditas"},{"key":"2025030417542647800_r4","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00251-008-0301-7","article-title":"Evolution of major histocompatibility complex by \u201cen bloc\u201d duplication before mammalian radiation","volume":"60","author":"Darbo","year":"2008","journal-title":"Immunogenetics"},{"key":"2025030417542647800_r5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/molbev\/msj002","article-title":"Conserved synteny between the Ciona genome and human paralogons identifies large duplication events in the molecular evolution of the insulin-relaxin gene family","volume":"23","author":"Olinski","year":"2006","journal-title":"Mol. 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