HSP90 as a global genetic modifier for male genital morphology in Drosophila melanogaster.

The molecular chaperone protein HSP90 has been proposed to modulate genotype-phenotype relationship in a broad range of organisms. We explore the proposed genetic modifier effect of HSP90 through a genomewide analysis. Here, we show that HSP90 functions as a genetic modifier of genital morphology in Drosophila melanogaster. We identified a large number of single-nucleotide polymorphisms (SNPs) with an HSP90-dependent effect by using genome wide association analysis. We classified the SNPs into the ones under capacitance effect (smaller allelic effect under HSP90 inhibition) or the ones under potentiation effect (larger allelic effect under HSP90 inhibition). Although the majority of SNPs are under capacitance, there are a large number of SNPs under potentiation. This observation provides support for a model in which Hsp90 is not described exclusively as a "genetic capacitor," but is described more broadly as a "genetic modifier." Because the majority of the candidate genes estimated from SNPs with an HSP90-dependent effect in the current study has never been reported to interact with HSP90 directly, the global genetic modifier effect of HSP90 may be exhibited through epistatic interactions in gene regulatory networks.

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