Changes in Alternative Splicing are Associated with Insecticide Response and Resistance.

Alternative splicing (AS) promotes phenotypic plasticity to adverse conditions by altering the transcripts of genes directly involved in adaptation to those conditions. Whether changes in AS occur in a few select genes or at a larger scale is unclear. Insect pests are regularly exposed to xenobiotic stress from insecticide applications and thus develop resistance. Here, we used a genome-wide approach to show that the fruit pest Drosophila suzukii, resistant to multiple insecticides, exhibits aberrant splicing in many classes of genes, including those involved in general stress response and processes previously implicated in insecticide resistance, such as metabolic and cuticular pathways. Our results suggest that resistance is not simply a consequence of broad, transcriptome-wide increases in AS events. Instead, the specific classes of genes that are differentially spliced are better determinants of insecticide resistance. Furthermore, we observe that sublethal insecticide exposure promotes AS events even in the absence of substantial differential gene expression. Based on our results, we propose that genetic accommodation could have led to the development of insecticide resistance in D. suzukii, in which repeated insecticide exposure alters the regulation of environmentally induced AS events, ultimately leading to genetic assimilation. This leads to elevated AS of specific transcripts, a phenomenon normally induced by insecticide exposure, potentially becoming genetically encoded and constitutively expressed, even in the absence of insecticide exposure. In summary, this study provides insights into the role of AS in enabling insects to diversify genome function to survive acute insecticide treatment and to develop xenobiotic resistance upon prolonged exposure.