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MBE Advance Access published online on June 8, 2005

Molecular Biology and Evolution, doi:10.1093/molbev/msi188
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Published by Oxford University Press 2005.
Accepted June 1, 2005

Research Article

Evolutionary Diversity and Potential Recombinogenic Role of Integration Targets of Non-LTR Retrotransposons

Andrew J. Gentles 1, Oleksiy Kohany 1, and Jerzy Jurka 1*

1 Genetic Information Research Institute, 1925 Landings Drive, Mountain View, CA 94043

* To whom correspondence should be addressed.
Jerzy Jurka, E-mail: jurka{at}girinst.org


   Abstract

Short interspersed elements (SINEs) make up a significant fraction of total DNA in mammalian genomes, providing a rich substrate for chromosomal rearrangements by SINE-SINE recombinations. Proliferation of mammalian SINEs is mediated primarily by LINE1 (L1) non-LTR retrotransposons that preferentially integrate at DNA sequence targets with average length ~15 bp and containing conserved endonucleolytic nicking signals at both ends. We report that sequence variations in the first of the two nicking signals, represented by a 5' TT-AAAA consensus sequence, affect the position of the second signal thus leading to target site duplications (TSDs) of different lengths. The length distribution of TSDs appears to be affected also by L1-encoded enzyme variants, since targets with the same 5' nicking site can be of different average length in different mammalian species. Taking this into account, we re-analyzed the second nicking site and found that it is larger and includes more conserved sites than previously appreciated, with a consensus of 5' ANTNTN-AA. We also studied potential involvement of the nicking sites in stimulating recombinations between SINE elements. We determined that SINE elements retaining TSDs with perfect 5' TT-AAAA nicking sites appear to be lost relatively rapidly from the human and rat genomes, and less rapidly from dog. We speculate that the introduction of single-strand DNA breaks induced by recurring endonucleolytic attacks at these sites, combined with the ubiquitousness of SINEs, may significantly promote recombination between repetitive elements, leading to the observed losses. At the same time new L1 subfamilies may be selected for "incompatibility" with pre-existing targets. This provides a possible driving force for the continual emergence of new L1 subfamilies which, in turn, may affect selection of L1-dependent SINE subfamilies.

Keywords: non-LTR retrotransposons; recombination; SINE integration targets.
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