The Flow of the Gibbon LAVA Element Is Facilitated by the LINE-1 Retrotransposition Machinery

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 LAVA(C), or its components, can be mobilized in the presence of the human L1 protein machinery. We show that L1 proteins mobilize the LAVA(C) element at frequencies exceeding processed pseudogene formation and human SVA(E) retrotransposition 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.