Comparative genomic analysis of prion genes

• Main Authors: Gamulin Vera, Premzl Marko
• Format: Article
• Language: English
• Published: BMC 2007-01-01
• Series: BMC Genomics
• Online Access: http://www.biomedcentral.com/1471-2164/8/1

<p>Abstract</p> <p>Background</p> <p>The homologues of human disease genes are expected to contribute to better understanding of physiological and pathogenic processes. We made use of the present availability of vertebrate genomic sequences, and we have conducted the most comprehensive comparative genomic analysis of the prion protein gene <it>PRNP </it>and its homologues, shadow of prion protein gene <it>SPRN </it>and doppel gene <it>PRND</it>, and prion testis-specific gene <it>PRNT </it>so far.</p> <p>Results</p> <p>While the <it>SPRN </it>and <it>PRNP </it>homologues are present in all vertebrates, <it>PRND </it>is known in tetrapods, and <it>PRNT </it>is present in primates. <it>PRNT </it>could be viewed as a TE-associated gene. Using human as the base sequence for genomic sequence comparisons (VISTA), we annotated numerous potential <it>cis</it>-elements. The conserved regions in <it>SPRN</it>s harbour the potential Sp1 sites in promoters (mammals, birds), C-rich intron splicing enhancers and PTB intron splicing silencers in introns (mammals, birds), and hsa-miR-34a sites in 3'-<it>UTR</it>s (eutherians). We showed the conserved <it>PRNP </it>upstream regions, which may be potential enhancers or silencers (primates, dog). In the <it>PRNP </it>3'-<it>UTR</it>s, there are conserved cytoplasmic polyadenylation element sites (mammals, birds). The <it>PRND </it>core promoters include highly conserved CCAAT, CArG and TATA boxes (mammals). We deduced 42 new protein primary structures, and performed the first phylogenetic analysis of all vertebrate prion genes. Using the protein alignment which included 122 sequences, we constructed the neighbour-joining tree which showed four major clusters, including shadoos, shadoo2s and prion protein-likes (cluster 1), fish prion proteins (cluster 2), tetrapode prion proteins (cluster 3) and doppels (cluster 4). We showed that the entire prion protein conformationally plastic region is well conserved between eutherian prion proteins and shadoos (18–25% identity and 28–34% similarity), and there could be a potential structural compatibility between shadoos and the left-handed parallel beta-helical fold.</p> <p>Conclusion</p> <p>It is likely that the conserved genomic elements identified in this analysis represent <it>bona fide cis</it>-elements. However, this idea needs to be confirmed by functional assays in transgenic systems.</p>