title: The Flow of the Gibbon LAVA Element Is Facilitated by the LINE-1 Retrotransposition Machinery.
abstract: LINE-Alu-VNTR-Alu-like (LAVA) elements comprise a family of non-autonomous, composite, non-LTR retrotransposons specific to gibbons and may have played a role in the evolution of this lineage. A full-length LAVA element consists of portions of repeats found in most primate genomes: CT-rich, Alu-like, and VNTR regions from the SVA retrotransposon, and portions of the AluSz and L1ME5 elements. To evaluate whether the gibbon genome currently harbors functional LAVA elements capable of mobilization by the endogenous LINE-1 (L1) protein machinery and which LAVA components are important for retrotransposition, we established a trans-mobilization assay in HeLa cells. Specifically, we tested if a full-length member of the older LAVA subfamily C that was isolated from the gibbon genome and named LAVAC, or its components, can be mobilized in the presence of the human L1 protein machinery. We show that L1 proteins mobilize the LAVACelement at frequencies exceeding processed pseudogene formation and human SVAEretrotransposition by > 100-fold and ≥3-fold, respectively. We find that only the SVA-derived portions confer activity, and truncation of the 3' L1ME5 portion increases retrotransposition rates by at least 100%. Tagged de novo insertions integrated into intronic regions in cell culture, recapitulating findings in the gibbon genome. Finally, we present alternative models for the rise of the LAVA retrotransposon in the gibbon lineage.
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon.|Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Meyer
authors.affiliation: Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Held
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Nevonen
authors.affiliation: Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.|Present address: Division of Inborn Metabolic Diseases, University Children's Hospital, Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Klawitter
authors.affiliation: Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pirzer
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon Gerald.Schumann@pei.de carbone@ohsu.edu.|Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon.|Department of Medicine, Oregon Health & Science University, Portland, Oregon.
authors.forename: Lucia
authors.initials: L
authors.lastname: Carbone
authors.affiliation: Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany Gerald.Schumann@pei.de carbone@ohsu.edu.
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Schumann
mesh_terms: D020087:Alu Elements; D000818:Animals; D016678:Genome; D006367:HeLa Cells; D006801:Humans; D006922:Hylobates / Q000235:genetics*; D020084:Long Interspersed Nucleotide Elements; D018598:Minisatellite Repeats; D011995:Recombination, Genetic
keywords: LAVA; LINE-1; gibbon; retrotransposon; trans-mobilization assay