title: Neofunctionalization in vertebrates: the example of retinoic acid receptors.
abstract: Understanding the role of gene duplications in establishing vertebrate innovations is one of the main challenges of Evo-Devo (evolution of development) studies. Data on evolutionary changes in gene expression (i.e., evolution of transcription factor-cis-regulatory elements relationships) tell only part of the story; protein function, best studied by biochemical and functional assays, can also change. In this study, we have investigated how gene duplication has affected both the expression and the ligand-binding specificity of retinoic acid receptors (RARs), which play a major role in chordate embryonic development. Mammals have three paralogous RAR genes--RAR alpha, beta, and gamma--which resulted from genome duplications at the origin of vertebrates. By using pharmacological ligands selective for specific paralogues, we have studied the ligand-binding capacities of RARs from diverse chordates species. We have found that RAR beta-like binding selectivity is a synapomorphy of all chordate RARs, including a reconstructed synthetic RAR representing the receptor present in the ancestor of chordates. Moreover, comparison of expression patterns of the cephalochordate amphioxus and the vertebrates suggests that, of all the RARs, RAR beta expression has remained most similar to that of the ancestral RAR. On the basis of these results together, we suggest that while RAR beta kept the ancestral RAR role, RAR alpha and RAR gamma diverged both in ligand-binding capacity and in expression patterns. We thus suggest that neofunctionalization occurred at both the expression and the functional levels to shape RAR roles during development in vertebrates.
authors.affiliation: Structure and Evolution of Nuclear Hormone Receptors, UMR 5161 du CNRS, INRA LA 1237, Laboratoire de Biologie Moléculaire de la Cellule, IFR128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Hector
authors.initials: H
authors.lastname: Escriva
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bertrand
authors.forename: Pierre
authors.initials: P
authors.lastname: Germain
authors.forename: Marc
authors.initials: M
authors.lastname: Robinson-Rechavi
authors.forename: Muriel
authors.initials: M
authors.lastname: Umbhauer
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cartry
authors.forename: Marilyne
authors.initials: M
authors.lastname: Duffraisse
authors.forename: Linda
authors.initials: L
authors.lastname: Holland
authors.forename: Hinrich
authors.initials: H
authors.lastname: Gronemeyer
authors.forename: Vincent
authors.initials: V
authors.lastname: Laudet
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D007798:Lampreys; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014981:Xenopus
chemical_list: D008024:Ligands; D018168:Receptors, Retinoic Acid; D012176:Retinoids