Identification in the human genome of mobile elements spread by DNA-mediated transposition

Abstract

We have identified in the human genome two families of mobile elements possessing the sequence characteristics of transposons that move directly from DNA to DNA rather than requiring the reverse transcription of an RNA intermediate. One type of element is closely related to the autonomous transposable element, mariner, and comprises a coding region for a transposase protein flanked by short terminal inverted repeat sequences (TIRs) of 31 or 32 bp. Elements of the second type form a family of short interspersed repetitive elements (SINEs) that are composed simply of two 37 bp TIRs surrounding six unique bps. The TIRs of the human mariner family are identical in all but one position to those of the SINE family, suggesting that the inverted-repeat SINEs represent non-autonomous transposable elements dependent on mariner-type transposase for mobility. Evidence for the mobility of both types of element is provided by examples of their integration into other repeat sequences and by the comparison of orthologous sites in cattle and human genomes. This evidence also shows that these elements have been active in DNA-mediated transposition at some point in the mammalian lineage. Therefore, it appears that the process of DNA-mediated transposition has occurred in mammalian cells and that its maximal cis-requirements are contained in the 80 bp consensus sequence of the human inverted-repeat SINE family.