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Prions may play crucial role in evolution.

Prions, abnormally folded proteins associated with several bizarre human diseases, may hold the key to a major mystery in evolution: how survival skills that require multiple genetic changes arise all at once when each genetic change by itself would be unsuccessful and even harmful.

In a study in the September 28, 2000, issue of Nature researchers at the Howard Hughes Institute at the University of Chicago describe a prion-dependent mechanism that seems perfectly suited to solving this dilemma, at least for yeast. It allows yeast to stockpile an arsenal of genetic variation and then release it to express a host of novel characteristics, including the ability to grow well in altered environments.

"We found that a heritable genetic element based on protein folding, not encoded in DNA or RNA, allows yeast to acquire many silent changes in their genome and suddenly reveal them," said Susan Lindquist, Ph.D., professor of molecular genetics and cell biology at the University of Chicago, Howard Hughes Investigator and principal author of the study.

There are thousands of proteins in every cell and each one has to fold into just the right shape in order to function. In prion diseases, which include mad cow disease and Creutzfeldt-Jakob disease, a normal cell protein, PrP, assumes an abnormal shape.

Mis-folded proteins are usually just degraded, but the prion protein causes other PrP proteins to mis-fold, too, creating a protein-folding chain reaction. Thus, they act as infectious agents. As more and more of the proteins fold into the prion shape, they form inactive aggregates which lead to dysfunction and disease.

A few years ago geneticists made the startling discovery that yeast, the organism found in bread and beer, has prions, too. Yeast prions are unrelated to the mammalian prions, and dont harm humans or yeast. They do, however, have the unusual property of mis-folding in the same peculiar way and spreading their change in
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Contact: Jeanne Galatzer-Levy
jgalatz@uchospitals.edu
773-702-6241
University of Chicago Medical Center
27-Sep-2000


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