Abstract
The prion protein (PrP) when misfolded into the pathogenic conformer PrPSc is the major causative agent of several lethal transmissible spongiform encephalopathies in mammals. Studies of evolutionary pressure on the corresponding gene using different datasets have yielded conflicting results. In addition, putative PrP or PrP interacting partners with strong similarity to PrP such as the doppel protein have not been examined to determine if the same evolutionary mechanisms apply to prion paralogs or if there are coselected sites that might indicate how and where the proteins interact. We examined several taxonomic groups that contain model organisms of prion diseases focusing on primates, bovids, and an expanded dataset of rodents for selection pressure on the prion gene (PRNP) and doppel gene (PRND) individually and for coevolving sites within. Overall, the results clearly indicate that both proteins are under strong selective constraints with relaxed selection on amino acid residues connecting α-helices 1 and 2.
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Acknowledgments
We thank the French ANR Biodiversity, Grant ANR 07 BDIV 012 CERoPath project (Community Ecology of Rodents and their Pathogens in a changing environment (www.ceropath.org), and the French ANR CP&ES, Grant ANR 11 CPEL 002 BiodivHealthSEA project (Local impacts and perceptions of global changes: Biodiversity and health in Southeast Asia) (www.biodivhealthsea.org) and all the CERoPath participants for their great help in field works. We also thank the Conservation Genetics Unit of the University of Liège and the Belgian Funds for the Scientific Research (FNRS) for supporting Johan Michaux. The provision of samples and support of the investigations by Jona Freise (Oldenburg), Hanan Sheikh Ali (Greifswald-Insel Riems) are kindly acknowledged. We acknowledge the help of Sergei L. Kosakovsky Pond with the programs HyPhy and Spidermonkey.
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Kyriakos Tsangaras, Sergios-Orestis Kolokotronis are considered joint first authors.
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Tsangaras, K., Kolokotronis, SO., Ulrich, R.G. et al. Negative Purifying Selection Drives Prion and Doppel Protein Evolution. J Mol Evol 79, 12–20 (2014). https://doi.org/10.1007/s00239-014-9632-1
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DOI: https://doi.org/10.1007/s00239-014-9632-1