Healthy change? Prions radically altered yeast cells' metabolisms.

Prions Show Their Better Side

Prion proteins are notorious for causing deadly brain diseases like bovine spongiform encephalopathy--better known as mad cow disease--and, in humans, Creutzfeld-Jakob disease. But prions may actually do some good in yeast. According to a new study, prions may infer an evolutionary advantage by allowing yeast cells to adapt quickly and radically when the environment changes.

Originally thought to be infectious agents, like viruses, prions are actually abnormally folded forms of naturally occurring proteins. They convert to the abnormal state either because of an inherited mutation or through contact with other abnormal proteins. But while prions that occur in mammals are clearly pathogenic, those in yeast are not.

Yeast's so-called PSI prion is a differently folded version of a protein normally responsible for heeding the so-called stop codon--a built-in part of the genetic code that halts the translation of DNA. Such stop codons make many genes inactive, or "silent," when they mistakenly occur in the middle of a gene rather than the end. Scientists suspect that these faulty genes may have also collected new mutations, some of which could be beneficial under certain circumstances. PSI could bring out these traits by "reading through" the stop codons.

To find out, University of Chicago molecular biologists Heather True and Susan Lindquist grew the normal and the PSI varieties of seven different yeast strains under a series of circumstances. As they report in the 28 September Nature, prions dramatically changed the success rate of each strain. They enabled some strains to grow on sugars they couldn't normally metabolize, while making others insensitive to certain antibiotics that would otherwise kill them. "We weren't expecting the degree of variation that we found in the prion forms," says Lindquist.

That variation suggests it may be advantageous for yeast to have prions, say the authors, noting that the changes would likely be reversible when yeast cells occasionally reverted back to their normal, unfolded state, which could be advantageous if conditions changed again. "It's a thoughtful and intelligent study," says molecular geneticist Ira Herskowitz from the University of California, San Francisco. "It provides intriguing evidence as to the biological significance of prions."

Related sites
Susan Lindquist's home page
Prion diseases, from Leicester University