Comparative analysis of the prion protein (PrP) gene in cetacean species

Abstract

The partial PrP gene sequence and the deduced protein of eight cetacean species, seven of which have never been reported so far, have been determined in order to extend knowledge of sequence variability of the PrP genes in different species and to aid in speculation on cetacean susceptibility to prions. Both the nucleotide and the deduced amino acid sequences have been analysed in comparison with some of the known mammalian PrPs. Cetacean PrPs present typical features of eutherian PrPs. The PrP gene from the species of the family Delphinidae gave identical nucleic acid sequences, while differences in the PrP gene were found in Balaenopteridae and Ziphidae. The phylogenetic tree resulting from analysis of the cetacean PrP gene sequences, together with reported sequences of some ungulates, carnivores and primates, showed that the PrP gene phylogenesis mirrors the species phylogenesis. The PrP gene of cetaceans is very close to species where natural forms of TSEs are known. From an analysis of the sequences and the phylogenesis of the PrP gene, susceptibility to or occurrence of prion diseases in cetaceans can not be excluded.

Unraveling the key to the resistance of canids to prion diseases

“…Given the idiosyncrasies of the causal agent of TSEs, the mechanism of the low susceptibility in some species may be due to a specific feature(s) of each PrP sequence and its misfolding proneness [ 28 ]. Comparative alignments of PrP sequences—taking into account the disease susceptibility of each species—is one of the preferred methods to search for low susceptibility determinants [ 19 , 29 – 33 ].…”

Loss of Octarepeats in Two Processed Prion Pseudogenes in the Red Squirrel, Sciurus vulgaris

“…Misfolded isoforms of PrP mediate the intra- and inter-species transmission of the mammalian prion diseases (transmissible spongiform encephalopathies, TSEs) (Kovacs and Budka 2009). Copper binding to PrP occurs extracellularly at the N -terminal domain, which in most mammals contains five or six repeats of a peptide of eight or nine residues with the consensus sequence P(Q/H)GGG(G/-)WGQ (Wopfner et al 1999; van Rheede et al 2003; Acutis et al 2007). This region can bind up to one Cu2 + ion per repeat (Viles et al 2008; Guerrieri et al 2009), but there is still no generally accepted role for the binding of copper to PrP (Davies and Brown 2008).…”