Human LINE retrotransposons generate processed pseudogenes

Long interspersed elements (LINEs) are endogenous mobile genetic elements(1 -4) that have dispersed and accumulated in the genomes of higher eukaryotes via germline transposition, with up to 100,000 copies in mammalian genomes . In humans, LINEs are the major source of insertional mutagenesis, being i nvolved in both germinal and somatic mutant phenotypes(4). Here we show tha t the human LINE retrotransposons, which transpose through the reverse tran scription of their own transcript(2), can also mobilize transcribed DNA not associated with a LIME sequence by a process involving the diversion of th e LINE enzymatic machinery by the corresponding mRNA transcripts. This resu lts in the 'retroposition' of the transcribed gene and the formation of new copies that disclose features characteristic of the widespread and natural ly occurring processed pseudogenes: loss of intron and promoter, acquisitio n of a poly(A) 3' end and presence of target-site duplications of varying l ength(5,6). We further show-by introducing deletions within either coding s equence of the human LINE-that both ORFs are necessary for the formation of the processed pseudogenes, and that retroviral-like elements are not able to produce similar structures in the same assay. Our results strengthen the unique versatility of LINEs as genome modellers.