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 gibbonsandmay haveplayeda role inthe evolutionof this lineage.Afull-lengthLAVAelement consists ofportions of repeats foundin 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)proteinmachinery andwhich LAVAcomponents areimportant for retrotransposition,we establishedatransmobilization assay in HeLa cells. Specifically, we tested if a full-length member of the older LAVA subfamily C thatwas isolated from the gibbon genome and namedLAVAC, or its components, can be mobilized in the presence of thehumanL1 protein machinery.We show that L1 proteins mobilize the LAVAC element at frequencies exceeding processed pseudogene formation and human SVAE retrotransposition by>100-fold and≥3-fold, respectively.Wefind that only theSVA-derived portions confer activity, and truncation of the30 L1ME5portion increases retrotranspositionrates by at least100%.Taggeddenovoinsertions integratedinto 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.