Nature 407, 477-483 (28 September 2000) | doi:10.1038/35035005; Received 31 May 2000; Accepted 24 July 2000

A yeast prion provides a mechanism for genetic variation and phenotypic diversity

Heather L. True & Susan L. Lindquist

  1. Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637, USA

Correspondence to: Correspondence and requests for materials should be addressed to S.L.L. (e-mail: Email:


A major enigma in evolutionary biology is that new forms or functions often require the concerted effects of several independent genetic changes. It is unclear how such changes might accumulate when they are likely to be deleterious individually and be lost by selective pressure. The Saccharomyces cerevisiae prion [PSI +] is an epigenetic modifier of the fidelity of translation termination, but its impact on yeast biology has been unclear. Here we show that [PSI +] provides the means to uncover hidden genetic variation and produce new heritable phenotypes. Moreover, in each of the seven genetic backgrounds tested, the constellation of phenotypes produced was unique. We propose that the epigenetic and metastable nature of [PSI +] inheritance allows yeast cells to exploit pre-existing genetic variation to thrive in fluctuating environments. Further, the capacity of [PSI +] to convert previously neutral genetic variation to a non-neutral state may facilitate the evolution of new traits.