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Nucleic Acids Research 2005 33(8):2374-2383; doi:10.1093/nar/gki531
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Published online 28 April 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Article

Transcribed processed pseudogenes in the human genome: an intermediate form of expressed retrosequence lacking protein-coding ability

Paul M. Harrison*, Deyou Zheng1, Zhaolei Zhang3, Nicholas Carriero2 and Mark Gerstein1,2

Department of Biology, McGill University Stewart Biology Building, 1205 Dr. Penfield Avenue, Montreal, Quebec, Canada H3A 1B1 1Department of Molecular Biophysics and Biochemistry, Yale University New Haven, CT, USA 2Department of Computer Science, Yale University New Haven, CT, USA 3Banting and Best Department of Medical Research, University of Toronto Toronto, Ontario, Canada

*To whom correspondence should be addressed. Tel: +1 514 398 6420; Fax: +1 514 398 5069; Email: paul.harrison{at}mcgill.ca

Received January 19, 2005. Revised March 14, 2005. Accepted April 4, 2005.

Pseudogenes, in the case of protein-coding genes, are gene copies that have lost the ability to code for a protein; they are typically identified through annotation of disabled, decayed or incomplete protein-coding sequences. Processed pseudogenes (P{Psi}gs) are made through mRNA retrotransposition. There is overwhelming genomic evidence for thousands of human P{Psi}gs and also dozens of human processed genes that comprise complete retrotransposed copies of other genes. Here, we survey for an intermediate entity, the transcribed processed pseudogene (TP{Psi}g), which is disabled but nonetheless transcribed. TP{Psi}gs may affect expression of paralogous genes, as observed in the case of the mouse makorin1-p1 TP{Psi}g. To elucidate their role, we identified human TP{Psi}gs by mapping expressed sequences onto P{Psi}gs and, reciprocally, extracting TP{Psi}gs from known mRNAs. We consider only those P{Psi}gs that are homologous to either non-mammalian eukaryotic proteins or protein domains of known structure, and require detection of identical coding-sequence disablements in both the expressed and genomic sequences. Oligonucleotide microarray data provide further expression verification. Overall, we find 166–233 TP{Psi}gs (~4–6% of P{Psi}gs). Proteins/transcripts with the highest numbers of homologous TP{Psi}gs generally have many homologous P{Psi}gs and are abundantly expressed. TP{Psi}gs are significantly over-represented near both the 5' and 3' ends of genes; this suggests that TP{Psi}gs can be formed through gene–promoter co-option, or intrusion into untranslated regions. However, roughly half of the TP{Psi}gs are located away from genes in the intergenic DNA and thus may be co-opting cryptic promoters of undesignated origin. Furthermore, TP{Psi}gs are unlike other P{Psi}gs and processed genes in the following ways: (i) they do not show a significant tendency to either deposit on or originate from the X chromosome; (ii) only 5% of human TP{Psi}gs have potential orthologs in mouse. This latter finding indicates that the vast majority of TP{Psi}gs is lineage specific. This is likely linked to well-documented extensive lineage-specific SINE/LINE activity. The list of TP{Psi}gs is available at: http://www.biology.mcgill.ca/faculty/harrison/tppg/bppg.tov (or) http:pseudogene.org.


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