Sleeping BeautyTransposition

Members of the Tc1/marinersuperfamily are probably the most widespread DNA transposons in nature (1). However, these elements appear to be transpositionally inactive in vertebrates due to the accumulation of mutations. In an attempt to isolate potentially active copies, we surveyed a number of fish genomes for the presence of Tc1-like elements from 11 different species. In summary, all the Tc1-like elements that we (2) and others (3,4) described from the different fish species were defective copies carrying inactivating mutations that accumulated over long evolutionary times. Nevertheless, careful sequence analysis allowed us to predict a consensus sequence that would likely represent an active archetypal sequence. We have engineered this sequence by eliminating the inactivating mutations from the transposase open reading frame. The resurrected synthetic transposon was named Sleeping Beauty(SB), in analogy of the Grimm brothers' famous fairy tale.SBcan be identical or closely related to an ancient transposon that once successfully invaded several fish genomes, in part by horizontal transmission between species (5). The resurrection of SB was the first demonstration that ancient transposable elements can be brought back to life. Before this work was published in 1997, there was no indication that any DNA-based transposon was active in vertebrates. SB not only represents the first DNA-based transposon ever shown to be active in cells of vertebrates, but the first functional gene ever reconstructed from inactive, ancient genetic material, for which an active, naturally occurring copy either does not exist or has not yet been isolated.