Prion proteins capable of evolution despite containing no DNA
Scientists say specialized proteins that cause mad cow disease are lifeless but can still evolve.
Mon, Jan 04, 2010 at 08:36 AM
PRION PATHOGENS: At least 20 fatal diseases are associated with abnormal prions, including the human form of mad cow disease. (Photo: Eye of Science/Science Photo Library)
Scientists from the Scripps Research Institute have shown for the first time that "lifeless" organic substances with no genetic material are capable of evolving just like any higher form of life. The discovery could reshape the definition of life and have revolutionary impacts on how certain diseases are treated.
The maleable substances in question are types of proteins called prions, which are also known for being the infectious agents blamed for causing mad cow disease and its human variant, Creutzfeldt-Jakob Disease.
Prior to the discovery of prions, it was thought that all pathogens required the use of nucleic acids, like DNA or RNA, to direct their replication. But prions are capable of propagating through the manipulation of their shape and the shape of surrounding proteins, essentially transmitting a misfolded protein state to their neighbors.
Of course, once they can replicate there's the potential for evolution via natural selection. But before the Scripps Research Institute's discovery, it was generally believed that prion structure was more stable than the structure of other infectious agents like viruses, which can mutate easily.
That view must now be amended. "On the face of it, you have exactly the same process of mutation and adaptive change in prions as you see in viruses," said Charles Weissmann, who led the study. "This means that this pattern of Darwinian evolution appears to be universally active."
In the study, the scientists transferred prion populations from brain cells to other cells in culture and observed how they changed. The two populations were then mixed again with both populations out-competing each other in their respective adapted environments.
In practical terms, the findings mean that prions can change to suit their environment and develop drug resistance. Thus, the work suggests that new approaches might be necessary to develop therapies for the diseases prions cause.
"This is a timely reminder that prion concerns are not going away and that controls to stop abnormal prions being transmitted to humans through the food system or through blood transfusions must be vigorously maintained," noted Professor John Collinge of the Medical Research Council's Prion Unit.