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MBE Advance Access published online on March 16, 2009
Molecular Biology and Evolution, doi:10.1093/molbev/msp050
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© The Author 2009. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

mRNA retrotransposition coupled with 5’ inversion as a possible source of new genes

Kenji K. Kojima and Norihiro Okada

Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology

Address for correspondence and reprints: Norihiro Okada, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuta-Cho, Midori-Ku, Yokohama, Japan. PHONE: +81-45-924-5742. FAX: +81-45-924-5835. E-mail: nokada{at}bio.titech.ac.jp.

Received for publication February 12, 2009. Revision received March 10, 2009. Accepted for publication March 10, 2009.

Human long interspersed nuclear element-1 (L1) occupies one-sixth of our genome and has contributed to genome evolution in various ways. Approximately 10% of human L1 copies are composed of two L1 segments; the 5' segment and 3' segment are in head-to-head (i.e., 5'-inverted) orientation. Besides mediating their own retrotransposition, L1 has the ability to mobilize mRNA in trans, and the number of retrotransposed mRNA sequences (retrocopies) is estimated to be >6,000. In this study, we identified 48 human-specific retrocopies and 95 chimpanzee-specific retrocopies by comparing the human and chimpanzee genomes. Among these retrocopies, 12 were 5'-inverted. The characteristics of these 5'-inverted retrocopies were similar to those of 5'-inverted L1 copies, indicating that the 5' inversion is generated by the same mechanism. With these findings, we examined the possibility that 5' inversion of the retrocopy generates a new gene that codes for a peptide with a different N terminus. We identified several potential 5'-inverted retrogenes, including those of thymopoietin beta (TMPO) and eukaryotic translation initiation factor 3 subunit 5 (EIF3F). The most interesting candidate was the 5'-inverted retrocopy of small nuclear ribonucleoprotein polypeptide N (SNRPN). This retrocopy was transcribed in the reverse orientation in several organs, had multiple transcript variants, and encoded a protein containing a peptide fragment derived from the N-terminal portion of SNRPN. Our results suggest that mRNA retrotransposition coupled with 5' inversion may be a mechanism to generate new genes distinct from parental genes.

Key Words: retrotransposition • retrocopy • retrogene • inversion • L1 • twin priming


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