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Science 30 September 2005:
Vol. 309. no. 5744, pp. 2185 - 2189
DOI: 10.1126/science.1118370
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Research Articles

Hsp90 Potentiates the Rapid Evolution of New Traits: Drug Resistance in Diverse Fungi

Leah E. Cowen and Susan Lindquist*

Hsp90 is a molecular chaperone for many signal transducers and may influence evolution by releasing previously silent genetic variation in response to environmental change. In fungi separated by ~800 million years of evolution, Hsp90 potentiated the evolution of drug resistance in a different way, by enabling new mutations to have immediate phenotypic consequences. Resistance was abrogated by Hsp90 inhibitors and by febrile temperatures, suggesting new therapeutic strategies and a clinical benefit of fever. During selection in a human host, drug resistance that was initially Hsp90-dependent evolved toward independence. Thus, Hsp90 can act in diverse ways to couple environmental contingency to the emergence and fixation of new traits.

Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.

* To whom correspondence should be addressed. E-mail: lindquist_admin{at}wi.mit.edu

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