Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions

Genome Biology

Cristina Vicente-García¹  Jaime J. Carvajal¹  Macarena López-Mayorga¹  Salvatore D’Aniello²  Fausto Ulloa³  Eduardo Soriano⁴  Jordi Garcia-Fernàndez⁵  Carlos Herrera-Úbeda⁵  Ester Antón-Galindo⁵  Enrique Navas-Pérez⁵  Gemma Marfany⁶  Bru Cormand⁶  Noèlia Fernàndez-Castillo⁶  Serena Mirra⁷  Demian Burguera⁸  José Luis Ferrán⁹  Rafael Falcón-Moya^1,10  Ángel M. Carrión^1,10  Antonio Rodríguez-Moreno^1,10  Irene Suárez-Pereira^1,11  Marta Alaiz-Noya^1,12  Pol Cuscó^1,13 

[1] Centro Andaluz de Biología del Desarrollo, CSIC-UPO-JA, Universidad Pablo de Olavide, 41013, Sevilla, Spain;Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, 80121, Naples, Italy;Department of Cell Biology, Physiology and Immunology, and Institute of Neurosciences, University of Barcelona, 08028, Barcelona, Spain;Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain;Department of Cell Biology, Physiology and Immunology, and Institute of Neurosciences, University of Barcelona, 08028, Barcelona, Spain;Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain;Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010, Barcelona, Spain;Department of Genetics, Microbiology and Statistics, Faculty of Biology, and Institut de Biomedicina (IBUB), University of Barcelona, 08028, Barcelona, Spain;Department of Genetics, Microbiology and Statistics, Faculty of Biology, and Institut de Biomedicina (IBUB), University of Barcelona, 08028, Barcelona, Spain;Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain;Institut de Recerca Sant Joan de Déu (IR-SJD), Esplugues de Llobregat, 08950, Barcelona, Spain;Department of Genetics, Microbiology and Statistics, Faculty of Biology, and Institut de Biomedicina (IBUB), University of Barcelona, 08028, Barcelona, Spain;Department of Cell Biology, Physiology and Immunology, and Institute of Neurosciences, University of Barcelona, 08028, Barcelona, Spain;Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain;Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain;Department of Genetics, Microbiology and Statistics, Faculty of Biology, and Institut de Biomedicina (IBUB), University of Barcelona, 08028, Barcelona, Spain;Department of Zoology, Charles University, Vinicna 7, 12844, Prague, Czech Republic;Department of Human Anatomy, School of Medicine, University of Murcia and IMIB-Arrixaca Institute, 30120, Murcia, Spain;Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, 41013, Sevilla, Spain;Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, 41013, Sevilla, Spain;Present Address: Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Neuropsychopharmacology and psychobiology research group, UCA, INiBICA, Cádiz, Spain;Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, 41013, Sevilla, Spain;Present Address: Instituto de Neurociencias de Alicante (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas), Alicante, Spain;Genome Architecture, Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), the Barcelona Institute of Science and Technology, 08003, Barcelona, Spain;Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain;

关键词: Genetic novelty;    Transposon domestication;    Bex3;    Tceal;    Placental mammals;    Gene cluster;    Neurodevelopmental disorders;    mTOR;    Autism spectrum disorder;   

DOI  :  10.1186/s13059-020-02172-3

来源: Springer

【 摘 要 】

BackgroundOne of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes at the core of key macroevolutionary changes, their origin and organismal function are generally poorly understood.ResultsHere, we identify several previously unreported transposable element domestication events in the human and mouse genomes. Among them, we find a remarkable molecular domestication that gave rise to a multigenic family in placental mammals, the Bex/Tceal gene cluster. These genes, which act as hub proteins within diverse signaling pathways, have been associated with neurological features of human patients carrying genomic microdeletions in chromosome X. The Bex/Tceal genes display neural-enriched patterns and are differentially expressed in human neurological disorders, such as autism and schizophrenia. Two different murine alleles of the cluster member Bex3 display morphological and physiopathological brain modifications, such as reduced interneuron number and hippocampal electrophysiological imbalance, alterations that translate into distinct behavioral phenotypes.ConclusionsWe provide an in-depth understanding of the emergence of a gene cluster that originated by transposon domestication and gene duplication at the origin of placental mammals, an evolutionary process that transformed a non-functional transposon sequence into novel components of the eutherian genome. These genes were integrated into existing signaling pathways involved in the development, maintenance, and function of the CNS in eutherians. At least one of its members, Bex3, is relevant for higher brain functions in placental mammals and may be involved in human neurological disorders.

【 授权许可】

CC BY