Identifying related L1 retrotransposons by analyzing 3′ transduced sequences -: art. no. R30

Background: A large fraction of the human genome is attributable to LI retrotransposon sequences. Not only do LIs themselves make up a significant portion of the genome, but LI-encoded proteins are thought to be responsible for the transposition of other repetitive elements and processed pseudogenes. In addition, LIs can mobilize non-LI, 3'-flanking DNA in a process called 3' transduction. Using computational methods, we collected DNA sequences from the human genome for which we have high confidence of their mobilization through LI-mediated 3' transduction. Results: The precursors of LIs with transduced sequence can often be identified, allowing us to reconstruct LI element families in which a single parent LI element begot many progeny LIs. Of the LIs exhibiting a sequence structure consistent with 3' transduction (LI with transduction-derived sequence, LI-TD), the vast majority were located in duplicated regions of the genome and thus did not necessarily represent unique insertion events. Of the remaining LI-TDs, some lack a clear polyadenylation signal, but the alignment between the parent-progeny sequences nevertheless ends in an A-rich tract of DNA. Conclusions: Sequence data suggest that during the integration into the genome of RNA representing an LI-TD, reverse transcription may be primed internally at A-rich sequences that lie downstream of the LI 3' untranslated region. The occurrence of LI-mediated transduction in the human genome may be less frequent than previously thought, and an accurate estimate is confounded by the frequent occurrence of segmental genomic duplications.