Transduction‐Specific ATLAS Reveals a Cohort of Highly Active L 1 Retrotransposons in Human Populations

L ong IN terspersed E lement‐1 ( LINE ‐1 or L 1) retrotransposons are the only autonomously active transposable elements in the human genome. The average human genome contains ∼80–100 active L1s, but only a subset of these L1s are highly active or ‘hot’. Human L1s are closely related in sequence, making it difficult to decipher progenitor/offspring relationships using traditional phylogenetic methods. However, L1 m RNA s can sometimes bypass their own polyadenylation signal and instead utilize fortuitous polyadenylation signals in 3′ flanking genomic DNA . Retrotransposition of the resultant m RNA s then results in lineage specific sequence “tags” (i.e., 3′ transductions) that mark the descendants of active L1 progenitors. Here, we developed a method (Transduction‐Specific Amplification Typing of L1 Active Subfamilies or TS ‐ ATLAS ) that exploits L1 3′ transductions to identify active L1 lineages in a genome‐wide context. TS ‐ ATLAS enabled the characterization of a putative active progenitor of one L1 lineage that includes the disease causing L1 insertion L1 RP , and the identification of new retrotransposition events within two other “hot” L1 lineages. Intriguingly, the analysis of the newly discovered transduction lineage members suggests that L1 polyadenylation, even within a lineage, is highly stochastic. Thus, TS ‐ ATLAS provides a new tool to explore the dynamics of L1 lineage evolution and retrotransposon biology. Long INterspersed Element‐1 (L1) retrotransposons are the only independently mobile elements in the human genome. We developed Transduction‐Specific Amplification Typing of L1 Active Subfamilies (TS‐ATLAS), which utilizes L1‐transduced genomic sequences, to identify a subset of highly active L1s genome‐wide. TS‐ATLAS enabled the characterization of the putative progenitor of an active disease‐causing L1 lineage, and identified new retrotransposition events within two other “hot” L1 lineages.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98809/1/humu22327.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98809/2/humu22327-sup-0001-si.pd