Journal
NUCLEIC ACIDS RESEARCH
Volume 33, Issue 8, Pages 2374-2383Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gki531
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Funding
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [P50HG002357] Funding Source: NIH RePORTER
- NHGRI NIH HHS [P50 HG02357-01, P50 HG002357] Funding Source: Medline
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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 (similar to 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: < URLREF > http://www.biology.mcgill.ca/faculty/harrison/tppg/bppg.tov URLREF > (or) < URLREF > http:pseudogene.org .
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