Structural Variants and Selective Sweep Foci Contribute to Insecticide Resistance in the <i>Drosophila</i> Genetic Reference Panel

Abstract

Patterns of nucleotide polymorphism within populations of <i>Drosophila melanogaster</i> suggest that insecticides have been the selective agents driving the strongest recent bouts of positive selection. However, there is a need to explicitly link selective sweeps to the particular insecticide phenotypes that could plausibly account for the drastic selective responses that are observed in these non-target insects. Here, we screen the Drosophila Genetic Reference Panel with two common insecticides; malathion (an organophosphate) and permethrin (a pyrethroid). Genome-wide association studies map survival on malathion to two of the largest sweeps in the <i>D. melanogaster</i> genome; <i>Ace</i> and <i>Cyp6g1</i> Malathion survivorship also correlates with lines which have high levels of <i>Cyp12d1</i>, <i>Jheh1</i> and <i>Jheh2</i> transcript abundance. Permethrin phenotypes map to the largest cluster of P450 genes in the Drosophila genome, however in contrast to a selective sweep driven by insecticide use, the derived allele seems to be associated with susceptibility. These results underscore previous findings that highlight the importance of structural variation to insecticide phenotypes: <i>Cyp6g1</i> exhibits copy number variation and transposable element insertions, <i>Cyp12d1</i> is tandemly duplicated, the <i>Jheh</i> loci are associated with a <i>Bari1</i> transposable element insertion, and a <i>Cyp6a17</i> deletion is associated with susceptibility.