{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:14:05Z","timestamp":1774689245732,"version":"3.50.1"},"reference-count":101,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T00:00:00Z","timestamp":1565568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diversity"],"abstract":"<jats:p>The vertebrate toll-like receptor (TLRs) supergene family is a first-line immune defense against viral and non-viral pathogens. Here, comparative evolutionary-genomics of 79 vertebrate species (8 mammals, 48 birds, 11 reptiles, 1 amphibian, and 11 fishes) revealed differential gain\/loss of 26 TLRs, including 6 (TLR3, TLR7, TLR8, TLR14, TLR21, and TLR22) that originated early in vertebrate evolution before the diversification of Agnatha and Gnathostomata. Subsequent dynamic gene gain\/loss led to lineage-specific diversification with TLR repertoires ranging from 8 subfamilies in birds to 20 in fishes. Lineage-specific loss of TLR8-9 and TLR13 in birds and gains of TLR6 and TLR10-12 in mammals and TLR19-20 and TLR23-27 in fishes. Among avian species, 5\u201310% of the sites were under positive selection (PS) (omega 1.5\u20132.5) with radical amino-acid changes likely affecting TLR structure\/functionality. In non-viral TLR4 the 20 PS sites (posterior probability PP &gt; 0.99) likely increased ability to cope with diversified ligands (e.g., lipopolysaccharide and lipoteichoic). For viral TLR7, 23 PS sites (PP &gt; 0.99) possibly improved recognition of highly variable viral ssRNAs. Rapid evolution of the TLR supergene family reflects the host\u2013pathogen arms race and the coevolution of ligands\/receptors, which follows the premise that birds have been important vectors of zoonotic pathogens and reservoirs for viruses.<\/jats:p>","DOI":"10.3390\/d11080131","type":"journal-article","created":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T04:31:21Z","timestamp":1565670681000},"page":"131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The Vertebrate TLR Supergene Family Evolved Dynamically by Gene Gain\/Loss and Positive Selection Revealing a Host\u2013Pathogen Arms Race in Birds"],"prefix":"10.3390","volume":"11","author":[{"given":"Imran","family":"Khan","sequence":"first","affiliation":[{"name":"CIIMAR\/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos, s\/n, 4450-208 Porto, Portugal"},{"name":"Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0084-6116","authenticated-orcid":false,"given":"Emanuel","family":"Maldonado","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos, s\/n, 4450-208 Porto, Portugal"}]},{"given":"Liliana","family":"Silva","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos, s\/n, 4450-208 Porto, Portugal"},{"name":"Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9874-933X","authenticated-orcid":false,"given":"Daniela","family":"Almeida","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos, s\/n, 4450-208 Porto, Portugal"}]},{"given":"Warren E.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Smithsonian Conservation Biology Institute, National Zoological Park, 1500 Remount Road, Front Royal, VA 22630, USA"},{"name":"The Walter Reed Biosystematics Unit, Museum Support Center MRC-534, Smithsonian Institution, 4210 Silver Hill Rd. Suitland, MD 20746, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7857-0757","authenticated-orcid":false,"given":"Stephen J.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199004, Russia"},{"name":"Guy Harvey Oceanographic Center, Halmos College of Natural Sciences and Oceanography, Nova Southeastern University, 8000 N. Ocean Drive, Ft Lauderdale, FL 33004, USA"}]},{"given":"Guojie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Section for Ecology and Evolution, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark"},{"name":"China National GeneBank, BGI-Shenzhen, Shenzhen 518083, China"},{"name":"State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China"}]},{"given":"Erich D.","family":"Jarvis","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics of Language, Box 54, Rockefeller University, New York, NY 10065, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, ML 20815, USA"}]},{"given":"M. Thomas P.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, \u00d8ster Volgade 5-7, 1350 Copenhagen, Denmark"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1328-1732","authenticated-orcid":false,"given":"Agostinho","family":"Antunes","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos, s\/n, 4450-208 Porto, Portugal"},{"name":"Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen Recognition and Innate Immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/35100529","article-title":"Toll-like receptors and innate immunity","volume":"1","author":"Medzhitov","year":"2001","journal-title":"Nat. Rev. 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