Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons

It has been suggested that the molecular chaperone protein Hsp90 (heat shock protein 90) is part of an evolutionarily conserved buffering mechanism that preserves the development process from phenotypic variance despite genetic and environmental perturbation. Specchia et al. offer an additional or an alternative mechanism whereby Hsp90 influences phenotypic variation by affecting the piRNA silencing mechanism leading to transposon activation. Phenotypic robustness in the face of genetic and environmental perturbations — known as canalization — relies on buffering mechanisms. Hsp90 chaperone machinery has been proposed to be an evolutionarily conserved buffering mechanism of phenotypic variance. Here, an additional, perhaps alternative, mechanism whereby Hsp90 influences phenotypic variation is proposed; Hsp90 mutations can generate new variation by transposon-mediated mutagenesis. The canalization concept1 describes the resistance of a developmental process to phenotypic variation, regardless of genetic and environmental perturbations, owing to the existence of buffering mechanisms. Severe perturbations, which overcome such buffering mechanisms, produce altered phenotypes that can be heritable and can themselves be canalized by a genetic assimilation process. An important implication of this concept is that the buffering mechanism could be genetically controlled. Recent studies on Hsp90, a protein involved in several cellular processes and development pathways2,3,4,5, indicate that it is a possible molecular mechanism for canalization and genetic assimilation. In both flies and plants, mutations in the Hsp90-encoding gene induce a wide range of phenotypic abnormalities, which have been interpreted as an increased sensitivity of different developmental pathways to hidden genetic variability6,7. Thus, Hsp90 chaperone machinery may be an evolutionarily conserved buffering mechanism of phenotypic variance, which provides the genetic material for natural selection. Here we offer an additional, perhaps alternative, explanation for proposals of a concrete mechanism underlying canalization. We show that, in Drosophila, functional alterations of Hsp90 affect the Piwi-interacting RNA (piRNA; a class of germ-line-specific small RNAs) silencing mechanism leading to transposon activation and the induction of morphological mutants. This indicates that Hsp90 mutations can generate new variation by transposon-mediated ‘canonical’ mutagenesis.