title: Negative purifying selection drives prion and doppel protein evolution.
abstract: The prion protein (PrP) when misfolded into the pathogenic conformer PrP(Sc) 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.
authors.affiliation: Department of Wildlife Diseases, Leibniz Institute for Zoo and Wildlife Research, Alfred-Kowalke-Str. 17, 10315, Berlin, Germany.
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Tsangaras
authors.forename: Sergios-Orestis
authors.initials: SO
authors.lastname: Kolokotronis
authors.forename: Rainer G
authors.initials: RG
authors.lastname: Ulrich
authors.forename: Serge
authors.initials: S
authors.lastname: Morand
authors.forename: Johan
authors.initials: J
authors.lastname: Michaux
authors.forename: Alex D
authors.initials: AD
authors.lastname: Greenwood
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011323:Primates; D011328:Prions / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012377:Rodentia; D012418:Ruminants; D012641:Selection, Genetic; D016415:Sequence Alignment
chemical_list: D011328:Prions