Prions show evolution without DNA: study

Infectious proteins that cause brain-wasting diseases such as BSE can evolve, even though they contain no genetic information, researchers say.

Scientists at the Scripps Research Institute in Florida found that prions can undergo mutations in their protein structure and those mutations can lead to changes in the disease, such as drug resistance.

Drug resistance is an evolutionary adaptation previously only seen in bacteria and viruses, organisms that carry genetic information in DNA or a similar nucleic acid molecule, RNA.

"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, head of Scripps Florida's department of infectology, in a statement.

"In viruses, mutation is linked to changes in nucleic acid sequence that leads to resistance. Now it's clear that you do not need nucleic acid for the process of evolution," Weissman said.

Prions are proteins that occur naturally in the cells of mammals. Infectious prions are abnormal, misshapen versions of this protein that cause neurodegenerative diseases such as Creutzfeldt-Jakob disease and BSE, also known as mad cow disease.

Prions "reproduce" by coming into contact with normal proteins and changing their shape to match their own, eventually forming long chains of abnormal proteins, leading to damage to the cells and tissues.

"It was generally thought that once cellular prion protein was converted into the abnormal form, there was no further change," Weissmann said. "Now we know that the abnormal prions replicate and create variants."

Natural selection

In their research, Scripps researcher Jiali Li and her colleagues found that natural selection would cause the more aggressive variants of the protein to take over the population.

In their experiment, the researchers transferred populations of prions from the brains of infected lab animals to cultures of cells. The prions adapted to their new environment, showing classic Darwinian evolution, and could out-compete prions adapted to the brain environment.

The scientists then introduced a drug to the cultures that has been found to inhibit certain prion strains. The number of infected cells fell dramatically, to seven per cent from 35 per cent.

They found that a drug-resistant variant of the prions became predominant in the cell culture, and the number of infected cells climbed to 25 per cent. When the drug was removed, the prion strain that was susceptible to the drug made a comeback and dominated the population again.

The evolution of drug resistance in prion diseases is an important finding for scientists searching for a treatment for these fatal illnesses.

The research was published online in the journal Science on Dec. 31.