title: LXRα and LXRβ Nuclear Receptors Evolved in the Common Ancestor of Gnathostomes.
abstract: Nuclear receptors (NRs) regulate numerous aspects of the endocrine system. They mediate endogenous and exogenous cues, ensuring a homeostatic control of development and metabolism. Gene duplication, loss and mutation have shaped the repertoire and function of NRs in metazoans. Here, we examine the evolution of a pivotal orchestrator of cholesterol metabolism in vertebrates, the liver X receptors (LXRs). Previous studies suggested that LXRα and LXRβ genes emerged in the mammalian ancestor. However, we show through genome analysis and functional assay that bona fide LXRα and LXRβ orthologues are present in reptiles, coelacanth and chondrichthyans but not in cyclostomes. These findings show that LXR duplicated before gnathostome radiation, followed by asymmetric paralogue loss in some lineages. We suggest that a tighter control of cholesterol levels in vertebrates was achieved through the exploitation of a wider range of oxysterols, an ability contingent on ligand-binding pocket remodeling.
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, U. Porto, Portugal.|Department of Biology, FCUP - Faculty of Sciences, U. Porto, Portugal.
authors.forename: Elza
authors.initials: E
authors.lastname: Fonseca
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, U. Porto, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Ruivo
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, U. Porto, Portugal.|ICBAS - Institute of Biomedical Sciences Abel Salazar - U. Porto, Portugal.
authors.forename: Mónica
authors.initials: M
authors.lastname: Lopes-Marques
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Biopolis, Singapore.
authors.forename: Huixian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, U. Porto, Portugal.|Department of Biology, FCUP - Faculty of Sciences, U. Porto, Portugal.
authors.forename: Miguel M
authors.initials: MM
authors.lastname: Santos
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Biopolis, Singapore.|Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Byrappa
authors.initials: B
authors.lastname: Venkatesh
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Centre of Marine and Environmental Research, U. Porto, Portugal.|Department of Biology, FCUP - Faculty of Sciences, U. Porto, Portugal.
authors.forename: L Filipe C
authors.initials: LF
authors.lastname: Castro
mesh_terms: D000818:Animals; D002784:Cholesterol; D019143:Evolution, Molecular; D050356:Lipid Metabolism; D000071518:Liver X Receptors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D014714:Vertebrates / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D000071518:Liver X Receptors; D002784:Cholesterol
keywords: cholesterol; chordates; liver X receptor; nuclear receptors