IDENTIFICATION IN THE HUMAN GENOME OF MOBILE ELEMENTS SPREAD BY DNA-MEDIATED TRANSPOSITION

We have identified in the human genome two families of mobile elements possessing the sequence characteristics of transposons that move dire ctly from DNA to DNA rather than requiring the reverse transcription o f an RNA intermediate. One type of element is closely related to the a utonomous transposable element, mariner, and comprises a coding region for a transposase protein flanked by short terminal inverted repeat s equences (TIRs) of 31 or 32 bp. Elements of the second type form a fam ily of short interspersed repetitive elements (SINEs) composed simply of two 37 bp TIRs surrounding six unique bps. The TIRs of the human ma riner family are identical in all but one position to those of the SIN E family, suggesting that the inverted-repeat SINEs represent non-auto nomous transposable elements dependent on mariner-type transposase for mobility: Evidence for the mobility of both types of element is provi ded by examples of their integration into other repeat sequences and b y the comparison of orthologous sites in cattle and human genomes. Thi s evidence also shows that these elements have been active in DNA-medi ated 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 containe d in the 80 bp consensus sequence of the human inverted-repeat SINE fa mily. (C) 1995 Academic Press Limited