Eukaryotic genomes contain numerous DNA transposons that move by a cut-and-paste mechanism. The majority of these elements are self-insufficient and dependent on their autonomous relatives to transpose. Miniature inverted repeat transposable elements (MITEs) are often the most numerous nonautonomous DNA elements in a higher eukaryotic genome. Little is known about the origin of these MITE families as few of them are accompanied by their direct ancestral elements in a genome. Analyses of MITEs in the yellow fever mosquito identified its youngest MITE family, designated as Gnome, that contains at least 116 identical copies. Genome-wide search for direct ancestral autonomous elements of Gnome revealed an elusive single copy Tc1/Mariner-like element, named as Ozma, that encodes a transposase with a DD37E triad motif. Strikingly, Ozma also gave rise to two additional MITE families, designated as Elf and Goblin. These three MITE families were derived at different times during evolution and bear internal sequences originated from different regions of Ozma. Upon close inspection of the sequence junctions, the internal deletions during the formation of these three MITE families always occurred between two microhomologous sites (6–8 bp). These results suggest that multiple MITE families may originate from a single ancestral autonomous element, and formation of MITEs can be mediated by sequence microhomology. Ozma and its related MITEs are exceptional candidates for the long sought-after endogenous active transposon tool in genetic control of mosquitoes.

Miniature inverted repeat transposable elements (MITEs) are often the most numerous DNA transposons in plant and animal genomes. The dramatic amplification of MITE families during evolution is puzzling, because the transposase sources for the vast majority of MITE families are unknown. The yellow fever mosquito genome contains > 220-Mb MITE sequences; however, transposition activity has not been demonstrated for any of the MITE families. The Gnome elements are the youngest MITE family in this genome, with at least 116 identical copies. To test whether the putative autonomous element Ozma is capable of mobilizing Gnome and its two sibling MITEs, analyses were performed in a yeast transposition assay system. Whereas the wild-type transposase resulted in very low transposition activity, mutations in the region containing a putative nuclear export signal motif resulted in a dramatic (at least 4160-fold) increase in transposition frequency. We have also demonstrated that each residue of the novel DD37E motif is required for the activity of the Ozma transposase. Footprint sequences left at the donor sites suggest that the transposase may cleave between the second and the third nucleotides from the 5' ends of the elements. The excised elements reinsert specifically at dinucleotide 'TA',~55% of them in yeast genes. The elements described in this article could potentially be useful as genetic tools for genetic manipulation of mosquitoes.