RT Journal Article
T1 Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions
A1 Navas-Pérez, Enrique
A1 Vicente-García, Cristina
A1 Mirra, Serena
A1 Burguera, Demian
A1 Fernàndez-Castillo, Noèlia
A1 Ferrán, José Luis
A1 López-Mayorga, Macarena
A1 Alaiz-Noya, Marta
A1 Suárez-Pereira, Irene
A1 Antón-Galindo, Ester
A1 Ulloa, Fausto
A1 Herrera-Úbeda, Carlos
A1 Cuscó, Pol
A1 Falcón-Moya, Rafael
A1 Rodríguez-Moreno, Antonio
A1 D’Aniello, Salvatore
A1 Cormand, Bru
A1 Marfany, Gemma
A1 Soriano, Eduardo
A1 Carrión Rodríguez, Ángel Manuel
A1 Carvajal, Jaime J.
A1 Garcia-Fernàndez, Jordi
K1 Genetic novelty
K1 Transposon domestication
K1 Bex3
K1 Tceal
K1 Placental mammals
K1 Gene cluster
K1 Neurodevelopmental disorders
K1 mTOR
K1 Autism spectrum disorder
AB 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.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.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.
PB Springer Nature
YR 2020
FD 2020-10-26
LK https://hdl.handle.net/10433/22857
UL https://hdl.handle.net/10433/22857
LA en
NO Navas-Pérez, E., Vicente-García, C., Mirra, S., Burguera, D., Fernàndez-Castillo, N., Ferrán, J. L., López-Mayorga, M., Alaiz-Noya, M., Suárez-Pereira, I., Antón-Galindo, E., Ulloa, F., Herrera-Úbeda, C., Cuscó, P., Falcón-Moya, R., Rodríguez-Moreno, A., D’Aniello, S., Cormand, B., Marfany, G., Soriano, E., … Garcia-Fernàndez, J. (2020). Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions. Genome Biology, 21(1), 267–267. https://doi.org/10.1186/s13059-020-02172-3
NO FundingMajor 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”). S.M. was first supported by a contract with the “Centro de Investigación Biomédica en Enfermedades Neurodegenerativas,” and later by “Centro de Investigación Biomédica en Red de Enfermedades Raras” (CIBERER). N.F.C. is also under contract by CIBERER. This study makes use of data generated by the DECIPHER community. A full list of centres who contributed to the generation of the data is available at http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Funding for the project was provided by the Wellcome Trust.
NO Departamento Fisiología, Anatomía y Biología Celular
NO Centro Andaluz de Biología del Desarrollo (CABD)
NO Department of Genetics, Microbiology and Statistics, Faculty of Biology, and Institut de Biomedicina (IBUB), University of Barcelona
DS RIO
RD Apr 23, 2026