Prion's progress: patterns and rates of molecular evolution in relation to spongiform disease

Modification of the cellular prion protein has been correlated with the acquisition of several neurodegenerative diseases, including kuru, scrapie, bovine spongiform encephalopathy (BSE), and Creutzfeldt-Jakob disease (CJD). Sequence conservation and amino acid identity are known to influence the ef...

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Bibliographic Details
Published in:Journal of molecular evolution 1998-08, Vol.47 (2), p.133-145
Main Authors: Krakauer, D.C. (University of Oxford, Oxford, UK.), Zanotto, P.M. de A, Pagel, M
Format: Article
Language:English
Subjects:
AMINO ACID SEQUENCES
AMINO ACID SUBSTITUTIONS
ANIMAL PROTEINS
Animals
Base Composition
BIOLOGICAL DIFFERENCES
Birds
Bovine spongiform encephalopathy
BRAIN
Cattle
CELLULAR PRION PROTEINS
CEREBRO
CHEMICAL COMPOSITION
COMPOSICION QUIMICA
COMPOSITION CHIMIQUE
Creutzfeldt-Jakob disease
DIFERENCIAS BIOLOGICAS
DIFFERENCE BIOLOGIQUE
ENCEPHALE
Encephalopathy, Bovine Spongiform - genetics
ENFERMEDADES INFECCIOSAS
Evolution, Molecular
Evolutionary biology
FILOGENIA
GENE
GENES
Genetic Variation
Genetics
Humans
INFECTIOUS DISEASES
MALADIE INFECTIEUSE
MAMIFEROS
MAMMALS
MAMMIFERE
Molecular biology
MUTACION
Mutagenesis
MUTATION
NONSYNONYMOUS SUBSTITUTIONS
NUCLEOTIDE SEQUENCE
NUCLEOTIDE SUBSTITUTIONS
PEPTIDE
PEPTIDES
PEPTIDOS
PHYLOGENIE
PHYLOGENY
Polymorphism, Genetic
POLYPEPTIDES
PRION
PRION DISEASES
Prion Diseases - genetics
PRIONES
PRIONS
Prions - genetics
PROTEINAS
PROTEINE
PROTEINS
PRP GENE
PRPC PROTEIN
Scrapie - genetics
SECUENCIA NUCLEOTIDICA
Selection, Genetic
SEQUENCE NUCLEOTIDIQUE
SPECIES DIFFERENCES
Spongiform encephalopathies
SYNONYMOUS SUBSTITUTIONS
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Description
Summary:Modification of the cellular prion protein has been correlated with the acquisition of several neurodegenerative diseases, including kuru, scrapie, bovine spongiform encephalopathy (BSE), and Creutzfeldt-Jakob disease (CJD). Sequence conservation and amino acid identity are known to influence the efficacy of interspecific transmission. We analyzed patterns of interspecific genetic variation with a view toward identifying features related to disease transmission. The reconstructed gene trees and amino acid tree were compared with the species tree, and all discordances observed were related to the species barrier of disease transmission. The rates of synonymous substitution, nonsynonymous substitution, and nucleotide content were determined for the protein-coding gene. Substitutions implicated in each of the prion diseases were found to occur in regions of the protein that are least variable across all species--opposite to the pattern of variability expected from interaction with an infectious pathogen. Amino acid residues related to the species barrier form a single cluster associated with the first alpha-helical domain of the protein. Residues related to sporadic and hereditary human prion disease form two separate clusters, associated with the second and third alpha-helical domains. Taken together, these results are consistent with the view that prion diseases arise from accidents in protein folding, rather than infection with an undiscovered virus-like particle. We speculate that the differences in disease phenotype between transmissable and hereditary forms could result from interactions between different parts of the protein during propagation
ISSN:0022-2844
1432-1432
DOI:10.1007/PL00006370