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Prions act as stepping stones in evolution

When a protein misfolds, the results can be disastrous. An incorrect change in the molecule's shape can lead to diseases including Alzheimer's and Huntington's. But scientists have discovered that misfolded proteins can have a positive side in yeast, helping cells navigate the dicey current of natural selection by expressing a variety of hidden genetic traits.

What's more, at the center of this process is a prion, a protein that changes shape in a self-perpetuating way--much like the prion in mammals that is responsible for certain neurological conditions such as Mad Cow disease.

"This is the first time we've seen a prion affect a cell in a beneficial way that can determine the evolution of an organism," says Heather True, lead author of the paper, which will appear August 15 in the online edition of the journal Nature.

Previously, True and Whitehead Institute Director Susan Lindquist reported that a particular yeast protein called Sup35 somehow altered the metabolic properties--or phenotype--of the cell when it "misfolded" into a prion state. Sup35 helps guide the process by which cells manufacture protein molecules. However, when Sup35 misfolds into its prion state, it forms amyloid fibers similar to those found in Alzheimer's patients and causes the cell's protein-producing machinery to go drastically awry.

More often than not, this is deleterious to the cell. In about 20% of the cases tested, however, the Whitehead team discovered that these new phenotypes afford the yeast cell a survival advantage.

"But we still didn't know the molecular mechanisms behind this," says True, a former postdoctoral researcher in the Lindquist lab, and now an assistant professor at Washington University, St. Louis. "How exactly did the prion change the appearance of the cell?"

The answer revealed a twist in the traditional understanding of how traits are inherited.

In order for Sup35 to ensure that the cell proper
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Contact: David Cameron
newsroom@wi.mit.edu
617-324-0460
Whitehead Institute for Biomedical Research
15-Aug-2004


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