Heads or tails: L1 insertion-associated 5' homopolymeric sequences

We report on loci with sequence architecture consistent with variants of the twin priming mechanism and introduce dual priming, a mechanism that could generate similar sequence characteristics. These insertions take the form of truncated L1s with hallmarks of classical TPRT insertions but having a poly(T) simple repeat at the 5' end of the insertion. We identified loci using computational analyses of the human, chimpanzee, orangutan, rhesus macaque and marmoset genomes. Insertion site characteristics for all putative loci were experimentally verified.The 39 loci that passed our computational and experimental screens probably represent inversion-deletion events which resulted in a 5' inverted poly(A) tail. Based on our observations of these loci and their local sequence properties, we conclude that they most probably represent twin priming events with unusually short non-inverted portions. We postulate that dual priming could, theoretically, produce the same patterns. The resulting homopolymeric stretches associated with these insertion events may promote genomic instability and create potential target sites for future retrotransposition events.Retrotransposons, mobile elements that move via a 'copy and paste' mechanism, called retrotransposition, are ubiquitous in primate genomes [1,2]. L1s, members of the long interspersed element (LINE) family of non-long terminal repeat (LTR) retrotransposons, which comprise as much as ~17% of primate genomes, are present in copy numbers of approximately 520,000 and have actively molded primate genomic architecture for the last 65 million years [3-5]. During their mobilization, they generate insertions containing L1 sequence and, in some cases, transduced sequence and deletion of adjacent genomic sequence [6-9]. Long after insertion, however, L1s can serve as sites of non-allelic homologous recombination, resulting in the loss, gain and inversion of genetic material [10,11]. In these ways, L1s have been shown to disrupt genes, ca