THE ROLE OF PRION DOMAINS IN EVOLUTION
Galina A. Zhouravleva
Department of Genetics, St. Petersburg State University, St. Petersburg, Russia
Prion (from proteinaceous infectious particles) is a protein isoform that is able to
convert the normal form of the same protein into prion form. This term was proposed by S.
Prusiner in 1982 to explain the unusual properties of pathogen transmission observed in the
cases of some neurodegenerative diseases in mammals. Examples of the “prion diseases”
include “mad cow disease”, or bovine spongiform encephalopathy (BSE), sheep scrapie
disease, and human Creutzfeldt-Jacob disease. Importance of prion diseases was emphasized
by the possibility of BSE transmission from cows to humans. Prion capability is not restricted
to PrP and can be found in the other proteins. Moreover, discovery of the yeast prions [PSI+],
[URE3] and others makes it clear that PrP represents just an extreme case of much more
common phenomenon. Experiments using yeast and fungal systems confirm that prion-like
phenomena are widespread, and identify the major components of the cellular machinery that
modulates prion formation and propagation.
The prion concept reveals a new mechanism of inheritance, which operates at the level
of the structural organization of proteins. Possibly, the prion formation is a pathological
process, while conservation of prion-forming potential in evolution is due to some adaptive
functions played by PFDs (prion forming domains) in certain conditions. As misfolded and
potentially aggregating proteins are usually accumulated during aging, it is an intriguing
possibility that aging could promote prion-like pathologies. Indeed, some aggregation-related
diseases (e.g., Alzheimer's disease) in humans are frequently associated with advanced age.
An alternative model suggests that prion formation by itself could be an adaptive process, so
that certain prions are responsible for the emergence of the adaptive traits. Various models,
explaining the biological roles and evolutionary conservation of prion-forming processes, and
relating them to the certain controversial aspects of the theory of evolution are discussed.
This work was supported by the Russian Foundation for Basic Research (03-0448886) and by the Presidium of RAN (Program “Biosphere origin and evolution”).