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Human Molecular Genetics Advance Access published online on March 26, 2009

Human Molecular Genetics, doi:10.1093/hmg/ddp152
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Large-scale analysis of exonized mammalian-wide interspersed repeats (MIRs) in primate genomes

Lan Lin1, Peng Jiang1, Shihao Shen2, Seiko Sato1, Beverly L. Davidson1,3,4 and Yi Xing1,5,*

1 Departments of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA 2 Departments of Biostatistics, University of Iowa, Iowa City, Iowa 52242, USA 3 Departments of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, USA 4 Departments of Neurology, University of Iowa, Iowa City, Iowa 52242, USA 5 Biomedical Engineering, University of Iowa, Iowa City, Iowa 52242, USA

* Corresponding Author: Yi Xing, Ph.D., Departments of Internal Medicine and Biomedical Engineering, 3294 CBRB, 285 Newton Rd, University of Iowa, Iowa City, IA, USA, 52242, EMAIL: yi-xing{at}uiowa.edu, TEL: (319)-384-3099, FAX: (319)-384-3150

Received February 20, 2009; Revised March 24, 2009; Accepted March 24, 2009

Transposable elements (TEs) are major sources of new exons in higher eukaryotes. Almost half of the human genome is derived from transposable elements, and many types of transposable elements have the potential to exonize. In this work, we conducted a large-scale analysis of human exons derived from mammalian-wide interspersed repeats (MIRs), a class of old transposable elements which was active prior to the radiation of placental mammals. Using exon array data of 328 MIR-derived exons and RT-PCR analysis of 39 exons in 10 tissues, we identified 15 constitutively spliced MIR exons, and 15 MIR exons with tissue-specific shift in splicing patterns. Analysis of RNAs from multiple species suggests that the splicing events of many strongly included MIR exons have been established before the divergence of primates and rodents, while a small percentage result from recent exonization during primate evolution. Interestingly, exon array data suggest substantially higher splicing activities of MIR exons as compared to exons derived from Alu elements, a class of primate-specific retrotransposons. This appears to be a universal difference between exons derived from young and old transposable elements, as it is also observed when comparing Alu exons to exons derived from LINE1 and LINE2, two other groups of old transposable elements. Together, this study significantly expands current knowledge about exonization of transposable elements. Our data imply that with sufficient evolutionary time, numerous new exons could evolve beyond the evolutionary intermediate state and contribute functional novelties to modern mammalian genomes.


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