Discovery of a functional retrotransposon of the murine phospholipid hydroperoxide glutathione peroxidase: chromosomal localization and tissue-specific expression pattern.
Phospholipid hydroperoxide glutathione peroxidase (PHGPx), a selenoprotein capable of reducing toxic hydroperoxy ester lipids, has been implicated in antioxidative defense and spermatogenesis. Screening a murine genomic library, we isolated two recombinants (pseudogenes 1 and 2) containing retrotransposons for this enzyme. On comparison with the paralogous cDNA, pseudogene 1 contained only two silent nucleotide exchanges, and the 3'-untranslated region (3'-UTR) carrying the functionally important selenocysteine insertion sequence was free of mutations. This retrotransposon was found in various mouse strains and could be mapped to the region B2-B3 of chromosome 10. In vitro studies indicated significant promoter activity in the 5'-flanking region of pseudogene 1, and we observed a tissuespecific expression of this retrotransposon. In the submandibular gland. Most PHGPx transcripts originated from pseudogene 1. In contrast, pseudogene 2, containing numerous mutations in all parts of the retrotransposon, was not expressed in any tissue. It was mapped to region E3-E4 of chromosome 17, and we did not detect any promoter activity in its 5'-flanking region. These data indicate the existence of two retrotransposed PHGPx pseudogenes, one of which encodes a functional enzyme. This retrotransposon belongs to the rare group of pseudogenes that are tissue-specifically expressed under the control of captured regulatory elements, and it constitutes an example of evolutionarily acquired redundancy in gene expression. The results are important for the design of future knockout strategies aimed at investigating the biological role of this enzyme.
Boschan
Carolin
C
Institute of Biochemistry, University Clinics Charité, Humboldt University, Monbijoustr.2, Berlin, D-10117, Germany.
Borchert
Astrid
A
Ufer
Christoph
C
Thiele
Bernd-Joachim
BJ
Kuhn
Hartmut
H
D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D002874:Chromosome Mapping; D005979:Glutathione Peroxidase / Q000235:genetics*; D007438:Introns / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D011401:Promoter Regions, Genetic / Q000235:genetics; D011544:Pseudogenes / Q000235:genetics*; D018626:Retroelements / Q000235:genetics*
D018626:Retroelements; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase