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Evidence for an epigenetic mechanism by which Hsp90 acts as a capacitor for morphological evolution

Nature Genetics volume 33, pages 7074 (2003) | Download Citation



Morphological alterations have been shown to occur in Drosophila melanogaster when function of Hsp90 (heat shock 90-kDa protein 1α, encoded by Hsp83) is compromised during development1. Genetic selection maintains the altered phenotypes in subsequent generations1. Recent experiments have shown, however, that phenotypic variation still occurs in nearly isogenic recombinant inbred strains of Arabidopsis thaliana2. Using a sensitized isogenic D. melanogaster strain, iso-KrIf-1, we confirm this finding and present evidence supporting an epigenetic mechanism for Hsp90's capacitor function, whereby reduced activity of Hsp90 induces a heritably altered chromatin state. The altered chromatin state is evidenced by ectopic expression of the morphogen wingless in eye imaginal discs and a corresponding abnormal eye phenotype, both of which are epigenetically heritable in subsequent generations, even when function of Hsp90 is restored. Mutations in nine different genes of the trithorax group that encode chromatin-remodeling proteins also induce the abnormal phenotype. These findings suggest that Hsp90 acts as a capacitor for morphological evolution through epigenetic and genetic mechanisms.

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We thank J. Kennison for providing fly stocks, G. Schubiger for recognizing that the ectopic outgrowths had triplicate vibrissae, T. Townes for suggesting the trichostatin A and sodium butyrate experiments and J. Horabin, S. Wilson and M. Bertram for reviewing the manuscript. This work was supported by Basil O'Connor Starter Scholar Research Awards to X.L. and D.M.R., a grant from the American Cancer Society to X.L. and grants from the US National Institutes of Health to X.L. and D.M.R.

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  1. Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

    • Vincent Sollars
  2. Department of Environmental Health Sciences, University of Alabama at Birmingham, RPHB 530, Birmingham, Alabama 35294-0022, USA.

    • Xiangyi Lu
    • , Li Xiao
    • , Mark D. Garfinkel
    •  & Douglas M. Ruden
  3. Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA.

    • Xiaoyan Wang


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The authors declare no competing financial interests.

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Correspondence to Douglas M. Ruden.

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