ScienceDaily (Jan. 3, 2010) — Scientists from The Scripps Research Institute have determined for the first time that prions, bits of infectious protein devoid of DNA or RNA that can cause fatal neurodegenerative disease, are capable of Darwinian evolution.
The study from Scripps Florida in Jupiter shows that prions can develop large numbers of mutations at the protein level and, through natural selection, these mutations can eventually bring about such evolutionary adaptations as drug resistance, a phenomenon previously known to occur only in bacteria and viruses. These breakthrough findings also suggest that the normal prion protein -- which occurs naturally in human cells -- may prove to be a more effective therapeutic target than its abnormal toxic relation.
The study was published in the December 31, 2009 issue of the journal Science Express, an advance, online edition of the journal Science.
"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."
Infectious prions (short for proteinaceous infectious particles) are associated with some 20 different diseases in humans and animals, including mad cow disease and a rare human form, Creutzfeldt-Jakob disease. All these diseases are untreatable and eventually fatal. Prions, which are composed solely of protein, are classified by distinct strains, originally characterized by their incubation time and the disease they cause. Prions have the ability to reproduce, despite the fact that they contain no nucleic acid genome.
Mammalian cells normally produce cellular prion protein or PrPC. During infection, abnormal or misfolded protein -- known as PrPSc -- converts the normal host prion protein into its toxic form by changing its conformation or shape. The end-stage consists of large assemblies (polymers) of these misfolded proteins, which cause massive tissue and cell damage.
"It was generally thought that once cellular prion protein was converted into the abnormal form, there was no further change," Weissmann said. "But there have been hints that something was happening. When you transmit prions from sheep to mice, they become more virulent over time. Now we know that the abnormal prions replicate, and create variants, perhaps at a low level initially. But once they are transferred to a new host, natural selection will eventually choose the more virulent and aggressive variants."...