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Transduction‐Specific ATLAS Reveals a Cohort of Highly Active L 1 Retrotransposons in Human Populations
Author(s) -
Macfarlane Catriona M.,
Collier Pamela,
Rahbari Raheleh,
Beck Christine R.,
Wagstaff John F.,
Igoe Samantha,
Moran John V.,
Badge Richard M.
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22327
Subject(s) - retrotransposon , biology , genetics , genome , lineage (genetic) , human genome , polyadenylation , computational biology , transposable element , gene , rna
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.