Ryan_Browlie_Whyard-Stress_Hsp90_Transposon

Abstract: Background: Transposable elements (TEs) have been recognized as potentially powerful drivers of genomic evolutionary change, but factors affecting their mobility and regulation remain poorly understood. Chaperones such as Hsp90 buffer environmental perturbations by regulating protein conformation, but are also part of the PIWI-interacting RNA pathway, which regulates genomic instability arising from mobile TEs in the germline. Stress-induced mutagenesis from TE movement could thus arise from functional trade-offs in the dual roles of Hsp90. Results: We examined the functional constraints of Hsp90 and its role as a regulator of TE mobility by exposing nematodes (Caenorhabditis elegans and C. briggsae) to environmental stressors, with and without RNAi-induced silencing of Hsp90. TE excision rates increased with environmental stress intensity at multiple loci in several strains of each species. These effects were compounded by RNAi-induced knockdown of Hsp90. Mutation frequencies at the unc-22 marker gene in the offspring of exposed animals mirrored the effects of our environmental stressors and RNAi-induced silencing of Hsp90. Conclusions: Our results support a role for Hsp90 in the suppression of TE mobility, and demonstrate that that these regulatory mechanisms can be overwhelmed with moderate environmental stressors. By affecting genomic stability in germline cells, stress-induced mutations arising from TE mobility and insertions affect the phenotype and genotype of subsequent generations. These findings have important implications for understanding stress-induced mutagenesis and genome evolutionary change.