Research Article

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

Science  30 Sep 2005:
Vol. 309, Issue 5744, pp. 2185-2189
DOI: 10.1126/science.1118370

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Abstract

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.

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