Intersecting experimental evolution and CRISPR screens to identify novel toxin resistance loci

Understanding toxin resistance in insects is key to appreciate niche adaptations but remains challenging due to its often-polygenic basis. A well-known example is the specialized association of Drosophila sechellia with noni fruit (Morinda citrifolia), which is toxic to most other insects, including the closely-related Drosophila simulans and Drosophila melanogaster. Toxicity of noni is due to its high concentration of octanoic acid (OA), but the mechanisms that determine sensitivity or resistance to OA in different species remain poorly understood. Here, we experimentally-evolved D. simulans with increased OA resistance, identifying multiple loci under selection. Cross-referencing these wit