{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:04:21Z","timestamp":1791453861902,"version":"4.3.3"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,3,7]]},"abstract":"<jats:p>\n                    The diversity of antigen receptors in the adaptive immune system of jawed vertebrates is generated by a unique process of somatic gene rearrangement known as V(D)J recombination. The Rag1 and Rag2 proteins are the key mediators of this process. They are encoded by a compact gene cluster that has exclusively been identified in animal species displaying V(D)J-mediated immunity, and no homologous gene pair has been identified in other organisms. This distinctly restricted phylogenetic distribution has led to the hypothesis that one or both of the\n                    <jats:italic>Rag<\/jats:italic>\n                    genes were coopted after horizontal gene transfer and assembled into a\n                    <jats:italic>Rag1\/2<\/jats:italic>\n                    gene cluster in a common jawed vertebrate ancestor. Here, we identify and characterize a closely linked pair of genes,\n                    <jats:italic>SpRag1L<\/jats:italic>\n                    and\n                    <jats:italic>SpRag2L<\/jats:italic>\n                    , from an invertebrate, the purple sea urchin (\n                    <jats:italic>Strongylocentrotus purpuratus<\/jats:italic>\n                    ) with similarity in both sequence and genomic organization to the vertebrate\n                    <jats:italic>Rag1<\/jats:italic>\n                    and\n                    <jats:italic>Rag2<\/jats:italic>\n                    genes. They are coexpressed during development and in adult tissues, and recombinant versions of the proteins form a stable complex with each other as well as with Rag1 and Rag2 proteins from several vertebrate species. We thus conclude that\n                    <jats:italic>SpRag1L<\/jats:italic>\n                    and\n                    <jats:italic>SpRag2L<\/jats:italic>\n                    represent homologs of vertebrate\n                    <jats:italic>Rag1<\/jats:italic>\n                    and\n                    <jats:italic>Rag2<\/jats:italic>\n                    . In combination with the apparent absence of V(D)J recombination in echinoderms, this finding strongly suggests that linked\n                    <jats:italic>Rag1<\/jats:italic>\n                    - and\n                    <jats:italic>Rag2<\/jats:italic>\n                    -like genes were already present and functioning in a different capacity in the common ancestor of living deuterostomes, and that their specific role in the adaptive immune system was acquired much later in an early jawed vertebrate.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0509720103","type":"journal-article","created":{"date-parts":[[2006,2,27]],"date-time":"2006-02-27T20:34:16Z","timestamp":1141072456000},"page":"3728-3733","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":153,"title":["An ancient evolutionary origin of the\n                    <i>Rag1<\/i>\n                    \/\n                    <i>2<\/i>\n                    gene locus"],"prefix":"10.1073","volume":"103","author":[{"given":"Sebastian D.","family":"Fugmann","sequence":"first","affiliation":[{"name":"*Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, MD 21224;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Messier","sequence":"additional","affiliation":[{"name":"Sunnybrook and Women\u2019s Research Institute and Department of Medical Biophysics, University of Toronto, 2075 Bayview Avenue, Room S-126B, Toronto, ON, Canada M4N 3M5; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Novack","sequence":"additional","affiliation":[{"name":"*Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, MD 21224;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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