Prions Evolve, Scripps Florida Study Finds

Prions, those mysterious bits of protein that can cause Creutzfeldt-Jakob disease , kuru , mad cow disease and scrapie, evolve according to Darwin's theory of evolution by natural selection. Researchers at The Scripps Research Institute's branch in Jupiter, Florida, announced the findings in the Dec. 31 online issue of the journal Science.

Prions are proteins that we all have. Prion diseases are caused by mistakes in folding these proteins. While DNA codes for making proteins, they form extremely intricate 3D structures that help determine their function. A misfolded protein, caused by some post-transcription error, can catalyze formation of other proteins, and the end result is prion disease. In other words, prion disease are not genetic diseases, although genes play a role in vulnerability.

Prions can evolve drug resistance and other beneficial mutations (from the prion's point of view, at least), like living things do, the study found. Prion diseases are remorseless and, as far as we know, 100 percent fatal, as the victims' brains are chewed away by the deadly protein.

It shouldn't be surprising that Darwinian evolution be found in prions, which after all are organic molecules. Darwin's insights have penetrated far afield from his original observation of evolution in whole organisms. Darwinian evolution has been used to design chemicals from mutation and directed selection of molecules, computerized and even used to create software programs .

From the press release:

"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 , M.D., Ph.D., the head of Scripps Florida's Department of Infectology, who led the study. "This means that this pattern of Darwinian evolution appears to be universally active. In viruses, mutation is linked to changes in nucleic acid sequence that leads to resistance. Now, this adaptability has moved one level down – to prions and protein folding – and it's clear that you do not need nucleic acid for the process of evolution."

"In the first part of the study, Weissmann and his colleagues transferred prion populations from infected brain cells to culture cells. When transplanted, cell-adapted prions developed and out-competed their brain-adapted counterparts, confirming prions' ability to adapt to new surroundings, a hallmark of Darwinian evolution. When returned to brain, brain-adapted prions again took over the population.

"To confirm the findings and to explore the issue of evolution of drug resistance, Weissmann and his colleagues used the drug swainsonine or swa, which is found in plants and fungi, and has been shown to inhibit certain prion strains. In cultures where the drug was present, the team found that a drug-resistant sub-strain of prion evolved to become predominant. When the drug was withdrawn, the sub-strain that was susceptible to swainsonine again grew to become the major component of the population.

"Weissmann notes that the findings have implications for the development of therapeutic targets for prion disease. Instead of developing drugs to target abnormal proteins, it could be more efficient to try to limit the supply of normally produced prions – in essence, reducing the amount of fuel being fed into the fire. Weissmann and his colleagues have shown some 15 years ago that genetically engineered mice devoid of the normal prion protein develop and function quite normally (and are resistant to prion disease!). . .


