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.

• Klíčová slova
• Autism spectrum disorder, Bex3, Gene cluster, Genetic novelty, Neurodevelopmental disorders, Placental mammals, Tceal, Transposon domestication, mTOR,
• MeSH
• CRISPR-Cas systémy MeSH
• DNA vazebné proteiny genetika   MeSH
• domestikace * MeSH
• fylogeneze MeSH
• jaderné proteiny genetika   MeSH
• lidé MeSH
• molekulární evoluce MeSH
• mozek MeSH
• multigenová rodina * MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• neurovývojové poruchy genetika   MeSH
• placenta MeSH
• placentálové genetika   MeSH
• poruchy autistického spektra genetika   MeSH
• proteiny nervové tkáně genetika   MeSH
• proteiny regulující apoptózu genetika   MeSH
• těhotenství MeSH
• TOR serin-threoninkinasy genetika   MeSH
• transkripční faktory genetika   MeSH
• transpozibilní elementy DNA * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BEX3 protein, human MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• jaderné proteiny MeSH
• Ngfrap1 protein, mouse MeSH Prohlížeč
• proteiny nervové tkáně MeSH
• proteiny regulující apoptózu MeSH
• TCEAL7 protein, human MeSH Prohlížeč
• TOR serin-threoninkinasy MeSH
• transkripční faktory MeSH
• transpozibilní elementy DNA * MeSH