Human Molecular Genetics, 2003, Vol. 12, No. 11 1321-1328
DOI: 10.1093/hmg/ddg138
© 2003 Oxford University Press
Trans mobilization of genomic DNA as a mechanism for retrotransposon-mediated exon shuffling
1Department of Radiological Sciences, Hiroshima Prefectural College of Health Sciences, 1-1 Gakuen-machi, Mihara, Hiroshima 723-0053, Japan and 2Hiroshima Prefecture Collaboration of Regional Entities for the Advancement of Technological Excellence, JST, 3-10-32 Kagamiyama, Higashihiroshima, Hiroshima 739-0046, Japan
Received December 17, 2002; Accepted March 24, 2003
Exon shuffling, the juxtaposition and new combinations of exons from different genes, facilitates evolutionary changes by increasing protein diversity or by generating new function. Exon shuffling is generated as a consequence of segmental duplications. Long interspersed element (LINE)-1 (L1)-mediated 3' transduction is a potential pathway for exon shuffling by which L1 associates 3' flanking DNA in cis as a read-through transcript and carries the DNA to a new genomic location. In this pathway, however, the targets are limited to the regions located 3' to L1s. Here we propose that the genomic DNA distant from L1 may be mobilized by an alternative (trans) action of L1. A partial ATM sequence containing a single exon and flanking introns has been retrotransposed to a new genomic location on chromosome 7. There was no L1 around the exon of the authentic ATM locus. An unusual feature that the poly(A) tail tagged to the transposed sequence oriented oppositely to the ATM's transcriptional orientation suggests that a trans action of reverse transcriptase on antisense transcript has driven the duplication of genomic DNA without removing introns. Taking account of similar duplication events in previous studies, a certain class of segmental duplications in the human genome may be accounted for by the trans action of retrotransposon machinery.
* To whom correspondence should be addressed. Tel: +81 848601171; Fax: +81 848601129; Email: ezima{at}hpc.ac.jp
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