Mol. Biol. Evol. 20(1):111-121. 2003
DOI: 10.1093/molbev/msg014
© 2003 by the Society for Molecular Biology and Evolution. ISSN: 0737-4038
Molecular Evolution of the Mammalian Prion Protein
Department of Biochemistry, NCMLS, University of Nijmegen, The Netherlands
Prion protein (PrP) sequences are until now available for only six of the 18 orders of placental mammals. A broader comparison of mammalian prions might help to understand the enigmatic functional and pathogenic properties of this protein. We therefore determined PrP coding sequences in 26 mammalian species to include all placental orders and major subordinal groups. Glycosylation sites, cysteines forming a disulfide bridge, and a hydrophobic transmembrane region are perfectly conserved. Also, the sequences responsible for secondary structure elements, for N- and C-terminal processing of the precursor protein, and for attachment of the glycosyl-phosphatidylinositol membrane anchor are well conserved. The N-terminal region of PrP generally contains five or six repeats of the sequence P(Q/H)GGG(G/-)WGQ, but alleles with two, four, and seven repeats were observed in some species. This suggests, together with the pattern of amino acid replacements in these repeats, the regular occurrence of repeat expansion and contraction. Histidines implicated in copper ion binding and a proline involved in 4-hydroxylation are lacking in some species, which questions their importance for normal functioning of cellular PrP. The finding in certain species of two or seven repeats, and of amino acid substitutions that have been related to human prion diseases, challenges the relevance of such mutations for prion pathology. The gene tree deduced from the PrP sequences largely agrees with the species tree, indicating that no major deviations occurred in the evolution of the prion gene in different placental lineages. In one species, the anteater, a prion pseudogene was present in addition to the active gene.
Key Words: prion protein • concerted evolution • BSE • Creutzfeldt-Jakob • pseudogene
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. J. Pushie and H. J. Vogel Molecular Dynamics Simulations of Two Tandem Octarepeats from the Mammalian Prion Protein: Fully Cu2+-bound and Metal-Free Forms Biophys. J., December 1, 2007; 93(11): 3762 - 3774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dong, J. D. Bloom, V. Goncharov, M. Chattopadhyay, G. L. Millhauser, D. G. Lynn, T. Scheibel, and S. Lindquist Probing the Role of PrP Repeats in Conformational Conversion and Amyloid Assembly of Chimeric Yeast Prions J. Biol. Chem., November 23, 2007; 282(47): 34204 - 34212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Martinez del Hoyo, M. Lopez-Bravo, P. Metharom, C. Ardavin, and P. Aucouturier Prion Protein Expression by Mouse Dendritic Cells Is Restricted to the Nonplasmacytoid Subsets and Correlates with the Maturation State J. Immunol., November 1, 2006; 177(9): 6137 - 6142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Eckhart, A. Uthman, W. Sipos, and E. Tschachler Genome Sequence Comparison Reveals Independent Inactivation of the Caspase-15 Gene in Different Evolutionary Lineages of Mammals Mol. Biol. Evol., November 1, 2006; 23(11): 2081 - 2089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Andrievskaia, H. McRae, C. Elmgren, H. Huang, A. Balachandran, and K. Nielsen Generation of Antibodies against Bovine Recombinant Prion Protein in Various Strains of Mice Clin. Vaccine Immunol., January 1, 2006; 13(1): 98 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Cancellotti, F. Wiseman, N. L. Tuzi, H. Baybutt, P. Monaghan, L. Aitchison, J. Simpson, and J. C. Manson Altered Glycosylated PrP Proteins Can Have Different Neuronal Trafficking in Brain but Do Not Acquire Scrapie-like Properties J. Biol. Chem., December 30, 2005; 280(52): 42909 - 42918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Novakofski, M. S. Brewer, N. Mateus-Pinilla, J. Killefer, and R. H. McCusker Prion biology relevant to bovine spongiform encephalopathy J Anim Sci, June 1, 2005; 83(6): 1455 - 1476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Lysek, C. Schorn, L. G. Nivon, V. Esteve-Moya, B. Christen, L. Calzolai, C. von Schroetter, F. Fiorito, T. Herrmann, P. Guntert, et al. Prion protein NMR structures of cats, dogs, pigs, and sheep PNAS, January 18, 2005; 102(3): 640 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Calzolai, D. A. Lysek, D. R. Perez, P. Guntert, and K. Wuthrich Prion protein NMR structures of chickens, turtles, and frogs PNAS, January 18, 2005; 102(3): 651 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Seabury, R. L. Honeycutt, A. P. Rooney, N. D. Halbert, and J. N. Derr Prion protein gene (PRNP) variants and evidence for strong purifying selection in functionally important regions of bovine exon 3 PNAS, October 19, 2004; 101(42): 15142 - 15147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. I. O'Rourke, T. R. Spraker, L. K. Hamburg, T. E. Besser, K. A. Brayton, and D. P. Knowles Polymorphisms in the prion precursor functional gene but not the pseudogene are associated with susceptibility to chronic wasting disease in white-tailed deer J. Gen. Virol., May 1, 2004; 85(5): 1339 - 1346. [Abstract] [Full Text] [PDF]
|
|