Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons

The canalization concept, first introduced by Waddington1, describes the resistance of a developmental process to phenotypic variation regardless of genetic and environmental perturbations, thanks to the existence of buffering mechanisms. Severe perturbations, which overcome such buffering mechanisms, produce altered phenotypes that can be heritable and then can themselves be canalized by a genetic assimilation process. An important implication of this concept is that the buffering mechanism itself could be genetically controlled. Recent studies on Hsp90, a protein involved in several cellular processes and development pathways2-5, seem to have identified it as 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. There has been a great interest in this proposal of a concrete mechanism underlying canalization. We would like to offer an additional, perhaps alternative, explanation for these observations. We show that, in Drosophila, functional alterations of Hsp90 affect the piRNA silencing mechanism leading to transposon activation and the induction of morphological mutants. This suggests that Hsp90 mutations can actually generate new variation by trasposon-mediated “canonical” mutagenesis.