Prions may play crucial role in evolution.

eritance of the prion state and the normal state. A spontaneous switch between the two states occurs approximately once in a million generations. Because a yeast colony produces a new generation every two hours, in a short time a colony will produce some members that have switched their state.

"Its an all or nothing switch, with the changes immediately inherited by all the progeny," said Lindquist. "But because the cell maintains the ability to switch back, the prion switch allows cells to occupy a new niche without losing their capacity to occupy the old."

The researchers exposed seven distinct genetic strains of yeast in their prion and non-prion states to 150 different growth conditions. The prion-positive state had a substantial effect on the growth of the yeast in nearly half of the conditions tested. In more than 25 percent of these cases its effects were positive. The incredible diversity of the advantages conveyed by the prions indicated that each strain had different novel genes turned on in its prion-positive state.

This prion switch is conserved in yeast across very distantly related genetic strains. Though the switch may have evolved as an accidental consequence of a shape change in an unimportant functioning part of the Sup35, its conservation suggests an evolutionary advantage.

"It may be that the prion switch offers yeast a way to respond to commonly fluctuating environments," said Lindquist. "During its evolution S. cerevisiae (brewers yeast) must have met with such erratic environments that it needed to maintain a global mechanism for exploiting genome-wide variation."

By providing yeast with a way to respond to fluctuating environments, the prion switch may offer a significant evolutionary advantage.

"Though we havent shown it yet, selective pressure should operate to fix the advantageous genes, which could then be read and translated at all times," said Lindquist.

Prion mechanisms could be more common

Contact: Jeanne Galatzer-Levy
University of Chicago Medical Center

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