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Cited by 2Evolution and Genetic DynamicsInsect Resistance and GeneticsNeurobiology and Insect Physiology Research

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

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Marconcini, Michele, Cruchet, Steeve, Goswami, Srishti, Viswanatha, Raghuvir, Butnaru, Matthew, De, Joydeep, Roselli, Camilla, Hadjieconomou, Dafni, Perrimon, Norbert, Mohr, Stephanie E, Benton, Richard·2026·eLife
DOI 10.7554/elife.111773.3

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Abstract

Understanding toxin resistance in insects is key to appreciating 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 other insects, including Drosophila simulans and Drosophila melanogaster . The main noni toxin is octanoic acid (OA), but the mechanisms that determine sensitivity or resistance to OA in different species remain unclear. Here, we experimentally evolved D. simulans with increased OA resistance, identifying multiple loci under selection. Cross-referencing these with a genome-wide, OA resistance CRISPR screen in a D. melanogaster cell line highlighted two proteins: Kraken, a putative detoxification enzyme expressed in digestive and renal tissues, and Alkbh7, a mitochondrial protein linked to fatty acid metabolism. Both genes show elevated expression in D. sechellia and OA-resistant D. simulans . In D. melanogaster , kraken mutants are more OA-sensitive, while Alkbh7 overexpression increased OA resistance. Mutation of these genes in D. sechellia reduced OA tolerance. Our identification of genes contributing to OA resistance in laboratory and natural contexts demonstrates how complementary selection approaches can provide insights into complex mechanisms of toxin susceptibility and adaptation. Such methods could have practical applications in the characterization of natural and artificial insecticides.

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Metadata

Authors
Marconcini, M., Cruchet, S., Goswami, S., Viswanatha, R., Butnaru, M., De, J., Roselli, C., Hadjieconomou, D., Perrimon, N., Mohr, S. E., & Benton, R.
Affiliations
  • University of Lausanne (CH)
  • Harvard University (US)
  • Howard Hughes Medical Institute (US)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Benton, Richard
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2026-09-11
Volume
15
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.111773.3
OpenAlex
W7212264776
Cited by
2
References
2
Citations by year
2026: 2
Type
posted content
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • eLife (acceptedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • PubMed Central (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
Funders
  • European Research Council (10.3030/101117267, 10.3030/833548)
  • Howard Hughes Medical Institute
  • Schweizerische Nationalfonds zur Förderung der wissenschaftlichen Forschung (310030_219185, 3200-0-239882)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Insect Resistance and Genetics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Keywords
toxin resistance, octanoic acid, Drosophila sechellia, Drosophila simulans, Drosophila melanogaster, experimental evolution, CRISPR screen, Kraken, noni fruit, insecticide resistance, polygenic adaptation, detoxification, fatty acid metabolism, niche adaptation

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