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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