LXRα and LXRβ nuclear receptors evolved in the common ancestor of gnathostomes

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 themammalian ancestor. However, we show through genomean alysis 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. © 2016 The Author.

We thank Neelakanteswar Aluru and Pedro Morais for the samples of little skate and amphioxus, respectively. This work was supported by Norte2020 and FEDER (Coral-Sustainable Ocean Exploitation-Norte-01-0145-FEDER- 000036), EXPL/MAR-EST/1540/2012. SFRH/BD/79305/2011 to E.F., SFRH/BD/84238/2012 to M.L.-M. and SFRH/BPD/72519/2010 to R.R. L.F.C.C. and M.M.S. are supported by the European Regional Development Fund (ERDF) through the COMPETE-Operational Competitiveness Programme and POPH-Operational Human Potential Programme and national funds through FCT-Foundation for Science and Technology (UID/Multi/04423/2013). This work was supported by the Branchiostoma lanceolatum genome consortium that provided access to the Branchiostoma lanceolatum genome sequence. We thank three anonymous reviewers for their comments and suggestions.