Transposition of Mutator-like Transposable Elements (MULEs) Resembles HAT and Transib Elements and V(D)J Recombination

Mutator-like transposable elements (MULEs) are widespread across fungal, plant and animal species. Despite their abundance and importance as genetic tools in plants, the transposition mechanism of the MULE superfamily was previously unknown. Discovery of the Muta1 element from Aedes aegypti and its successful transposition in yeast facilitated the characterization of key steps in Muta1 transposition. Here we show that purified transposase binds specifically to the Muta1 ends and catalyzes excision through double strand breaks (DSB) and the joining of newly excised transposon ends with target DNA. In the process, the DSB forms hairpin intermediates on the flanking DNA side. Analysis of transposase proteins containing site-directed mutations revealed the importance of the conserved DDE motif and a W residue. The transposition pathway resembles that of the V(D)J recombination reaction and the mechanism of hAT and Transib transposases including the importance of the conserved W residue in both MULEs and hATs. In addition, yeast transposition and in vitro assays demonstrated that the terminal motif and subterminal repeats of the Muta1 terminal inverted repeat also influence Muta1 transposition. Collectively, our data provides new insights to understand the evolutionary relationships between MULE, hAT and Transib elements and the V(D)J recombinase.