Study: Prions Can Be Helpful Engine of Evolution, Rather than Cause of Disease

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By Sarah Zhang
Feb 18, 2012 12:18 AMNov 20, 2019 12:54 AM

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Yeast under a microscope.

What's the News: Prions

get a bad name---the very word is a portmanteau of "protein" and "infection," which suggests that they're up to no good. And there's obviously some truth to this: Prions are a type of protein that have alternative folded forms, and if they aggregate into insoluble clumps, they can cause problems like mad cow disease. But prions might also be a key part of evolution. A new survey published in

 Nature

found prions in 1/3 of yeast strains, and 40% of the traits they conferred were beneficial. How the Heck:

  • The study's authors had a key tool for studying prions in yeast: a protein called Hsp104 that is known to turn prions into their active, aggregating form. If knocking out Hsp104 changes how a yeast strain behaves, that's a sign the strain has prions.

  • After screening 4 isolates of 690 yeast strains in 12 different culturing conditions both with and without Hsp104 (that's 66,240 total samples, if you're not doing the math), the researchers concluded that prions exist in 1/3 of the strains. Yeast prions are sometimes thought to be artifacts of growth conditions in a petri dish, so the big, diverse set of samples lends credence to the alternative hypothesis that they are in fact common in nature.

  • The scientists also looked at two prions [PSI^+] and [MOT3^+] in detail and found that inactivating a prion could make the yeast strain better or worse at resisting toxins, depending on the strain. How can one change account for such diverse responses? [PSI^+] , [MOT3^+] and the 23 other known yeast prions tend to be master switches that change protein translation and RNA transcription, say the researchers. That makes them well-suited for affecting large changes in stressful conditions.

  • It's like hedging a bet, say the researchers. Sometimes the activated prion will make yeast more sensitive to a stressor, but any prion that's beneficial will spread among the survivors. In wild yeast, 40% of the "new" traits from activated prions were actually beneficial.

What's the Context:

  • It is controversial and novel to say that prions are a common mechanism for generating diversity, especially diversity that proves helpful. The study's lead author, Susan Lindquist, and her effort to gain acceptance for her ideas are featured in the latest issue of

    Nature

    along with the paper.

  • Prions are also noteworthy for being an epigenetic form of inheritance, which means they don't alter any DNA sequence yet still change an organism's traits. Activated prions will turn on any other proteins like itself that it encounters, so prions in the cytoplasm can perpetuate their activated form in daughter cells.

The Future Holds:

  • Prions are weird things, and scientists are still grappling with why they exist and what they do. If Dr. Linquist's hypothesis proves right, they're a hitherto unstudied evolutionary mechanism, and understanding that could help us understand how they flare up to cause neurodegenerative disease.

Reference: Halfmann et al. Prions are a common mechanism for phenotypic inheritance in wild yeasts. Nature. 16 February 2012. DOI: 10.1038/nature10875

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