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

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• dc.contributor.author Navas Pérez, Enrique
• dc.contributor.author Cuscó Pons, Pol, 1987-
• dc.contributor.author García Fernàndez, Jordi
• dc.date.accessioned 2020-11-13T07:31:06Z
• dc.date.available 2020-11-13T07:31:06Z
• dc.date.issued 2020
• dc.description.abstract Background: One 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. Results: Here, 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. Conclusions: We 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.
• dc.description.sponsorship Major financial support for this research was received from Spanish “Ministerio de Ciencia, Innovación y Universidades.” Grants BFU2015-68655-P and BFU2017-861152-P to J.G.F., RTI2018-100968-B-I00, 2017-SGR-738, H2020/2014-2020 under grant agreements n°667302, n°643051, and n°728018 to B.C., PGC2018-098229-B-I00 to J.L.F., BES-2016-077374 to E.A.-G., CVI-7290 Junta de Andalucía to A.R.M., SAF2016-80937-R (Ministerio de Economía y Competitividad/FEDER) to G.M., Institutional Grant MDM-2016-0687 (Maria de Maeztu Excellence Unit, Department of Gene Regulation and Morphogenesis at CABD) and BFU2017-83150-P to J.J.C, BFU2017-89780-R and P12-CTS-2257 to A.M.C. and SAF2016-76340-R and María de Maeztu Excellence Unit, Institute of Neurosciences to E.S.. E.N.P. held an FPI pre-doctoral fellowship (Spanish “Ministerio de Ciencia, Innovación y Universidades”).
• dc.format.mimetype application/pdf
• dc.identifier.citation Navas-Pérez E, Vicente-García C, Mirra S, Burguera D, Fernàndez-Castillo N, Ferrán JL et al. Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions. Genome Biol. 2020; 21(1):267. DOI: 10.1186/s13059-020-02172-3
• dc.identifier.doi http://dx.doi.org/10.1186/s13059-020-02172-3
• dc.identifier.issn 1474-7596
• dc.identifier.uri http://hdl.handle.net/10230/45752
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof Genome Biol. 2020; 21(1):267
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/667302
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68655-P
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-861152-P
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/643051
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/728018
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-80937-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-83150-P
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-89780-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-89780-R
• dc.rights © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data ma
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Autism spectrum disorder
• dc.subject.keyword Bex3
• dc.subject.keyword Gene cluster
• dc.subject.keyword Genetic novelty
• dc.subject.keyword Neurodevelopmental disorders
• dc.subject.keyword Placental mammals
• dc.subject.keyword Tceal
• dc.subject.keyword Transposon domestication
• dc.subject.keyword mTOR
• dc.title Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion