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Research ArticlesHsp90 Potentiates the Rapid Evolution of New Traits: Drug Resistance in Diverse Fungi
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 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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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. 
Science. ISSN 0036-8075 (print), 1095-9203 (online)
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