Published online 2 April 2009 | Nature | doi:10.1038/news.2009.231

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The beneficial side of prions

The infectious agents could aid yeast survival in harsh conditions.

Germinating yeast cells.Some prions appear to help yeast survive.Punchstock

Prions, the mis-folded proteins best known for causing diseases such as bovine spongiform encephalopathy in cows, scrapie in sheep and Creutzfeldt–Jakob disease in humans, could also help yeast survival, according to a study in the journal Cell1.

"We think prions are really important," says co-author Simon Alberti of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. "When environmental conditions are harsh, they might allow a species to survive."

The work, led by Susan Lindquist of the Whitehead Institute, bolsters the theory that prions might confer an evolutionary advantage, says Alberti. Lindquist first broached that idea nine years ago, after finding that a prion called PSI+ in the yeast Saccharomyces cerevisiae triggered heritable changes that could provide a way of adapting to fluctuating environments2. More recent work also suggests prions might play a role in memory in sea slugs and smell in mice.

In the new work, a scan of the S. cerevisiae genome yielded 24 potential prion-forming proteins. Only five prions were known to exist in yeast before this study.

The team focused on a protein called Mot3 and found that it can twist into a prion form. When in its normal shape, Mot3 suppresses yeast genes involved in building the cellular wall. But when Mot3 kinks into a prion, it loses this function and the wall-building genes activate. Hence, yeast carrying the Mot3 prions grew thicker, more robust cell walls.

Under some conditions — such as low oxygen availability — a thicker wall will help yeast survive, says co-author Randal Halfmann, also at the Whitehead Institute.

Hedging bets

In about 1 in 10,000 yeast cells, Mot3 spontaneously twisted into prions, the researchers found. In yeast, prions can be transmitted from generation to generation without the transmission of genetic material, so most of the daughter cells also carried the prion form of Mot3.

Hence, in any given population of yeast, some colonies are likely to be carrying the prion form of Mot3 and thicker cell walls. "It is a bet-hedging strategy," says Halfmann.

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The research "represents a new step in our appreciation of prions and prion biology, and may lead us to a better understanding of their biological function, which is still pretty murky, especially in animals", says Willard Eyestone, a prion expert at Virginia Tech University in Blacksburg.

The work should also help researchers to identify previously unknown prions in organisms with sequenced genomes. That's because the 24 yeast prions the team identified contained an over-abundance of the amino acids glutamine and asparagine. Halfmann says the team is already searching the genomes of other organisms. A parade of prions could soon arrive. "We have much better predictive power now," says Alberti. 

  • References

    1. Alberti, S., Halfmann, R., King, O., Kapila, A. & Lindquist, S. Cell 137, 146–158 (2009). | Article |
    2. True, H. L. & Lindquist, S. Nature 407, 477–483 (2000). | Article | PubMed | ISI | ChemPort |
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