Population bulk segregant mapping uncovers resistance mutations and the mode of action of a chitin synthesis inhibitor in arthropods

  1. Van Leeuwen, T. 5
  2. Demaeght, P. 5
  3. Osborne, E.J. 2
  4. Dermauw, W. 5
  5. Gohlke, S. 4
  6. Nauen, R. 1
  7. Grbić, M. 36
  8. Tirry, L. 5
  9. Merzendorfer, H. 4
  10. Clark, R.M. 2
  1. 1 Bayer CropScience AG, Research Pest Control, D-40789 Monheim, Germany
  2. 2 University of Utah
    info

    University of Utah

    Salt Lake City, Estados Unidos

    ROR https://ror.org/03r0ha626

  3. 3 University of Western Ontario
    info

    University of Western Ontario

    London, Canadá

    ROR https://ror.org/02grkyz14

  4. 4 University of Osnabrück
    info

    University of Osnabrück

    Osnabrück, Alemania

    ROR https://ror.org/04qmmjx98

  5. 5 Ghent University
    info

    Ghent University

    Gante, Bélgica

    ROR https://ror.org/00cv9y106

  6. 6 Instituto de Ciencias de la Vid y del Vino
    info

    Instituto de Ciencias de la Vid y del Vino

    Logroño, España

    ROR https://ror.org/01rm2sw78

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Revista:
Proceedings of the National Academy of Sciences of the United States of America

ISSN: 0027-8424

Año de publicación: 2012

Volumen: 109

Número: 12

Páginas: 4407-4412

Tipo: Artículo

DOI: 10.1073/PNAS.1200068109 PMID: 22393009 SCOPUS: 2-s2.0-84858674174 GOOGLE SCHOLAR

Otras publicaciones en: Proceedings of the National Academy of Sciences of the United States of America

Repositorio institucional: lock_openAcceso abierto Editor

Resumen

Because of its importance to the arthropod exoskeleton, chitin biogenesis is an attractive target for pest control. This point is demonstrated by the economically important benzoylurea compounds that are in wide use as highly specific agents to control insect populations. Nevertheless, the target sites of compounds that inhibit chitin biogenesis have remained elusive, likely preventing the full exploitation of the underlying mode of action in pest management. Here, we show that the acaricide etoxazole inhibits chitin biogenesis in Tetranychus urticae (the two-spotted spider mite), an economically important pest. We then developed a population-level bulk segregant mapping method, based on high-throughput genome sequencing, to identify a locus for monogenic, recessive resistance to etoxazole in a field-collected population. As supported by additional genetic studies, including sequencing across multiple resistant strains and genetic complementation tests, we associated a nonsynonymous mutation in the major T. urticae chitin synthase (CHS1) with resistance. The change is in a C-terminal transmembrane domain of CHS1 in a highly conserved region that may serve a noncatalytic but essential function. Our finding of a target-site resistance mutation in CHS1 shows that at least one highly specific chitin biosynthesis inhibitor acts directly to inhibit chitin synthase. Our work also raises the possibility that other chitin biogenesis inhibitors, such as the benzoylurea compounds, may also act by inhibition of chitin synthases. More generally, our genetic mapping approach should be powerful for high-resolution mapping of simple traits (resistance or otherwise) in arthropods.