TY - JOUR
T1 - Transcribed processed pseudogenes in the human genome
T2 - An intermediate form of expressed retrosequence lacking protein-coding ability
AU - Harrison, Paul M.
AU - Zheng, Deyou
AU - Zhang, Zhaolei
AU - Carriero, Nicholas
AU - Gerstein, Mark
N1 - Funding Information:
Thanks to T. Bureau, N. Juretic and D. Hoen (McGill U.) for discussions. This work was supported in part by a Discovery Grant from the National Science and Engineering Council of Canada to P.M.H., and by National Institutes of Health grant # P50 HG02357-01 to M.G. Funding to pay the Open Access publication charges for this article was provided by McGill University.
PY - 2005
Y1 - 2005
N2 - 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 (TPψgs) are made through mRNA retrotransposition. There is overwhelming genomic evidence for thousands of human Pψgs 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 (TPψg), which is disabled but nonetheless transcribed. TPψgs may affect expression of paralogous genes, as observed in the case of the mouse makorin1-p1 TPψgs. To elucidate their role, we identified human TPψgs by mapping expressed sequences onto Pψgs and, reciprocally, extracting TPψgs from known mRNAs. We consider only those Pψgs 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 TPψgs (∼4-6% of Pψgs). Proteins/transcripts with the highest numbers of homologous TPψgs generally have many homologous Pψgs and are abundantly expressed. TPψgs are significantly over-represented near both the 5′ and 3′ ends of genes; this suggests that TPψgs can be formed through gene-promoter co-option, or intrusion into untranslated regions. However, roughly half of the TPψgs are located away from genes in the intergenic DNA and thus may be co-opting cryptic promoters of undesignated origin. Furthermore, TPψgs are unlike other Pψgs 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 TPψgs have potential orthologs in mouse. This latter finding indicates that the vast majority of TPψgs is lineage specific. This is likely linked to well-documented extensive lineage-specific SINE/LINE activity. The list of TPψgs is available at: http://www.biology.mcgill.ca/faculty/harrison/tppg/bppg.tov (or) http:pseudogene.org.
AB - 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 (TPψgs) are made through mRNA retrotransposition. There is overwhelming genomic evidence for thousands of human Pψgs 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 (TPψg), which is disabled but nonetheless transcribed. TPψgs may affect expression of paralogous genes, as observed in the case of the mouse makorin1-p1 TPψgs. To elucidate their role, we identified human TPψgs by mapping expressed sequences onto Pψgs and, reciprocally, extracting TPψgs from known mRNAs. We consider only those Pψgs 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 TPψgs (∼4-6% of Pψgs). Proteins/transcripts with the highest numbers of homologous TPψgs generally have many homologous Pψgs and are abundantly expressed. TPψgs are significantly over-represented near both the 5′ and 3′ ends of genes; this suggests that TPψgs can be formed through gene-promoter co-option, or intrusion into untranslated regions. However, roughly half of the TPψgs are located away from genes in the intergenic DNA and thus may be co-opting cryptic promoters of undesignated origin. Furthermore, TPψgs are unlike other Pψgs 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 TPψgs have potential orthologs in mouse. This latter finding indicates that the vast majority of TPψgs is lineage specific. This is likely linked to well-documented extensive lineage-specific SINE/LINE activity. The list of TPψgs is available at: http://www.biology.mcgill.ca/faculty/harrison/tppg/bppg.tov (or) http:pseudogene.org.
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U2 - 10.1093/nar/gki531
DO - 10.1093/nar/gki531
M3 - Article
C2 - 15860774
AN - SCOPUS:17844396017
SN - 0305-1048
VL - 33
SP - 2374
EP - 2383
JO - Nucleic acids research
JF - Nucleic acids research
IS - 8
ER -