Yeast find use for misfolded proteins

Clumps might help single-celled organisms adapt to hardship

A special set of misfolded proteins known as prions may offer yeast a trial run at different traits before permanent changes are made to the genetic code, a new study finds.

In yeast, prions cause a wide variety of new characteristics that are not wired into DNA but can still be passed on to daughter cells. The changes might act like prototypes that cells can try out before incorporating them into nucleic acid, scientists at the Whitehead Institute for Biomedical Research in Cambridge, Mass. report in the Feb. 16 Nature.

“This is opening up a whole new world of work for scientists and a whole new world for people to understand how evolution occurs,” says Yury Chernoff, a biologist at the Georgia Institute of Technology.

For the most part, prions have attracted attention because some variant forms cause diseases, like Creutzfeldt-Jakob disease in people and scrapie in sheep. 

In prion states, proteins change shape and cause other proteins to change conformation too. These misshapen proteins come together to form organized clumps, or amyloids. These clumps stop the individual proteins from functioning properly.

Though these protein clumps had been identified in many types of yeast grown in artificial lab conditions, it was unclear whether prions in yeast played a biologically important and nonharmful role out in the wild.

Whitehead Institute researcher Susan Lindquist and colleagues in her lab tackled these unknowns by screening over 700 strains of yeast. Many of these strains were collected from natural sources, such as soil, insects and human patients.

One-third of the yeast contained clumps of misfolded proteins.

The group paid particular attention to yeast that contained clumps of Sup35, a protein involved in making sure that a cell’s proteins are cut to the right length.

Some types of yeast with Sup35 clumps were able to adapt under stressful conditions, such as in environments with high acidity or that contain DNA-damaging drugs. Certain adaptive advantages also appeared in yeast containing clumps of Mot3, a protein that mediates the transcription of cell wall–building genes.

Overall, about 40 percent of changes brought on by the protein clumps appeared to boost yeast growth under stressful conditions, the scientists found. 

Scientists are not sure exactly how these traits might become incorporated into the yeast genetic code.

Still, Randal Halfmann, an author of the new study who is now at UT Southwestern Medical Center at Dallas, says these findings suggest that prions introduce flexible changes to yeast to test out before hardwiring the traits into the DNA.

“We’ve found these prions in hundreds of strains and they are conferring all kinds of really interesting biology to the cells,” Lindquist says. “This isn’t just an interesting or cool little oddity.”

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