{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:08:08Z","timestamp":1777446488641,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T00:00:00Z","timestamp":1557446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["Project No. 031342"],"award-info":[{"award-number":["Project No. 031342"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>To appraise how evolutionary processes, such as gene duplication and loss, influence an organism\u2019s xenobiotic sensitivity is a critical question in toxicology. Of particular importance are gene families involved in the mediation of detoxification responses, such as members of the nuclear receptor subfamily 1 group I (NR1I), the pregnane X receptor (PXR), and the constitutive androstane receptor (CAR). While documented in multiple vertebrate genomes, PXR and CAR display an intriguing gene distribution. PXR is absent in birds and reptiles, while CAR shows a tetrapod-specific occurrence. More elusive is the presence of PXR and CAR gene orthologs in early branching and ecologically-important Chondrichthyes (chimaeras, sharks and rays). Therefore, we investigated various genome projects and use them to provide the first identification and functional characterization of a Chondrichthyan PXR from the chimaera elephant shark (Callorhinchus milii, Holocephali). Additionally, we substantiate the targeted PXR gene loss in Elasmobranchii (sharks and rays). Compared to other vertebrate groups, the chimaera PXR ortholog displays a diverse expression pattern (skin and gills) and a unique activation profile by classical xenobiotic ligands. Our findings provide insights into the molecular landscape of detoxification mechanisms and suggest lineage-specific adaptations in response to xenobiotics in gnathostome evolution.<\/jats:p>","DOI":"10.3390\/ijms20092331","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T03:57:07Z","timestamp":1557719827000},"page":"2331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Evolutionary Plasticity in Detoxification Gene Modules: The Preservation and Loss of the Pregnane X Receptor in Chondrichthyes Lineages"],"prefix":"10.3390","volume":"20","author":[{"given":"Elza S. S.","family":"Fonseca","sequence":"first","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, 4450-208 Matosinhos, Portugal"},{"name":"FCUP\u2014Faculty of Sciences, Department of Biology, University of Porto, 4150-177 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2412-8730","authenticated-orcid":false,"given":"Raquel","family":"Ruivo","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6857-7581","authenticated-orcid":false,"given":"Andr\u00e9 M.","family":"Machado","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, 4450-208 Matosinhos, Portugal"}]},{"given":"Francisca","family":"Conrado","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, 4450-208 Matosinhos, Portugal"}]},{"given":"Boon-Hui","family":"Tay","sequence":"additional","affiliation":[{"name":"Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore 138673, Singapore"}]},{"given":"Byrappa","family":"Venkatesh","sequence":"additional","affiliation":[{"name":"Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore 138673, Singapore"}]},{"given":"Miguel M.","family":"Santos","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, 4450-208 Matosinhos, Portugal"},{"name":"FCUP\u2014Faculty of Sciences, Department of Biology, University of Porto, 4150-177 Porto, Portugal"}]},{"given":"L. Filipe C.","family":"Castro","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, 4450-208 Matosinhos, Portugal"},{"name":"FCUP\u2014Faculty of Sciences, Department of Biology, University of Porto, 4150-177 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.cell.2006.06.049","article-title":"Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network","volume":"126","author":"Bookout","year":"2006","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13951","DOI":"10.1021\/acs.est.8b04399","article-title":"Evolutionary Exploitation of Vertebrate Peroxisome Proliferator-Activated Receptor \u03b3 by Organotins","volume":"52","author":"Ishii","year":"2018","journal-title":"Environ. Sci. 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