Journal of Molecular Evolution

, Volume 68, Issue 3, pp 205–207

Positive Selection in Prion Protein


DOI: 10.1007/s00239-008-9176-3

Cite this article as:
Premzl, M. & Gamulin, V. J Mol Evol (2009) 68: 205. doi:10.1007/s00239-008-9176-3


The prion diseases, such as Creutzfeldt-Jakob disease of humans and bovine spongiform encephalopathy, involve the aberrant metabolism and accumulation of prion protein PrP. There are three contradictory hypotheses about evolution of prion protein gene PRNP. Population genetic studies have proposed that PRNP could be under balancing selection, strong purifying selection, or mainly positive selection. We made use of the maximum likelihood tests for detection of positive selection at the amino acid level and present availability of PRNP coding sequences to contribute to these disagreements. Positive selection could occur at amino acids residing in active sites, and at amino acids involved in protein-protein interactions. Thus we tested a hypothesis that positive selection at the amino acid level in PrP might have taken place in human and related species from the superordinal group Euarchonta, as well as in bovine and related species from the superordinal clade Laurasiatheria. Our study and the present experimental evidences indicate that positive selection at the amino acid level might have taken place in the PrP signal sequences and conformationally plastic PrP regions, as well as at the protein X binding sites.


Positive selection Prion diseases Prion protein Protein X Signal sequence Species barrier 

Supplementary material

239_2008_9176_MOESM1_ESM.eps (286 kb)
Additional data file 1PRNP phylogenies. The ML phylogenetic trees of the Euarchonta (a) and Laurasiatheria (b) PRNPs were determined using PHYLIP using default settings ( We used these topologies for our ML tests for detection of positive selection at the amino acid level. Branch lengths were estimated using the M0 model (number of nucleotide substitutions per codon) (Wong et al. 2004). The foreground branches are indicated. PRNP GenBank accession numbers: Bos taurus AJ298878, Camelus dromedarius Y09760, Canis familiaris DQ444488, Cynocephalus variegatus AY133034, Diceros bicornis AY133052, Equus caballus AY133051, Erinaceus europaeus BN001181, Homo sapiens M13899, Macaca mulatta U08307, Manis sp. AY133050, Microcebus murinus DQ014540, Myotis lucifugus BN000992, Pongo pygmaeus abelii EMBL acc. number BN000848, Pteropus vampyrus BN000994, Saimiri sciureus U08310, Sorex araneus BN001182, Sus scrofa L07623, Talpa europaea AY133042, Tupaia tana AY133035. We annotated the E. europaeus and S. araneusPRNP coding sequences as the third party annotations and submitted them to EBI ( (Eps 286 kb)

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Molecular BiologyRudjer Boskovic InstituteZagrebCroatia

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