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J. Biol. Chem., Vol. 281, Issue 1, 16-19, January 6, 2006

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Adult Tissue-specific Expression of a Dppa3-derived Retrogene Represents a Postnatal Transcript of Pluripotent Cell Origin^*

Stephen J. Elliman1, Isaac Wu1, and Daniel M. Kemp2

From the Diabetes and Metabolism Disease Area, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139 and the Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Processed pseudogenes emerge by reverse transcription of spliced mRNAs followed by incorporation of the resultant cDNA into the genome. Their genesis requires that retrotransposition occurs within the germ line, a provision that significantly limits random distribution of source genes. We previously identified embryonic stem cell-specific genes as an enriched source of retropseudogene origin. Nanog, Oct4, and Dppa3 (Stella/PGC7) presented as source genes for >30 processed pseudogenes within the human genome. In the current study, we extended our previous analysis and focused on the pluripotent cell-specific Dppa gene family. Of the five Dppa genes characterized, four were associated with putative retropseudogenes as determined by nucleotide BLAST (basic local alignment sequence tool) searches of the respective mRNA transcripts against the human genome. A subset of the 11 Dppa3-derived hits were then screened against a human adult tissue cDNA panel for evidence of transcriptional activity. One of the putative Dppa3-derived retropseudogenes, Dppa3(d), located on human chromosome 16p13, tested positive for mRNA transcript in bone marrow, peripheral blood, pancreas, adrenal gland, and thyroid gland. Specificity against the source Dppa3 gene expression was sequence verified, and independent human tissue samples were obtained to confirm Dppa3(d) expression. These data substantiate the existence of human adult tissue-specific transcripts that originate via retrotransposition of the pluripotent cell-specific gene, Dppa3. Further studies may reveal an evolutionary role for this example of genetic diversity, but in the short term our observations serve a cautionary purpose regarding the use of Dppa3 transcripts in adult tissue-derived cells as a potential marker of pluripotency.

Received for publication, October 14, 2005

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ These authors contributed equally to this work.

² To whom correspondence should be addressed: Diabetes & Metabolism Disease Area, Novartis Institutes for BioMedical Research, 100 Technology Square, Cambridge, MA 02139. Tel.: 617-817-0105; Fax: 617-871-7051; E-mail: daniel.kemp{at}novartis.com.

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