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Science 335 (6068): 574-578

Copyright © 2012 by the American Association for the Advancement of Science

Natural Variation in a Chloride Channel Subunit Confers Avermectin Resistance in C. elegans

Rajarshi Ghosh, Erik C. Andersen, Joshua A. Shapiro, Justin P. Gerke,* Leonid Kruglyak{dagger}

Abstract: Resistance of nematodes to anthelmintics such as avermectins has emerged as a major global health and agricultural problem, but genes conferring natural resistance to avermectins are unknown. We show that a naturally occurring four-amino-acid deletion in the ligand-binding domain of GLC-1, the alpha-subunit of a glutamate-gated chloride channel, confers resistance to avermectins in the model nematode Caenorhabditis elegans. We also find that the same variant confers resistance to the avermectin-producing bacterium Streptomyces avermitilis. Population-genetic analyses identified two highly divergent haplotypes at the glc-1 locus that have been maintained at intermediate frequencies by long-term balancing selection. These results implicate variation in glutamate-gated chloride channels in avermectin resistance and provide a mechanism by which such resistance can be maintained.

Lewis-Sigler Institute for Integrative Genomics, Department of Ecology and Evolutionary Biology, and Howard Hughes Medical Institute, Princeton University, Princeton, NJ 08544, USA.

* Present address: Pioneer Hi-Bred International, A DuPont Business, Johnston, IA 50131, USA

{dagger} To whom correspondence should be addressed. E-mail: leonid{at}genomics.princeton.edu (L.K.)

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Multiple Instances of Ancient Balancing Selection Shared Between Humans and Chimpanzees.
E. M. Leffler, Z. Gao, S. Pfeifer, L. Segurel, A. Auton, O. Venn, R. Bowden, R. Bontrop, J. D. Wall, G. Sella, et al. (2013)
Science 339, 1578-1582
   Abstract »    Full Text »    PDF »
Glutamate-gated Chloride Channels.
A. J. Wolstenholme (2012)
J. Biol. Chem. 287, 40232-40238
   Abstract »    Full Text »    PDF »
Surviving in a Toxic World.
A. J. Wolstenholme (2012)
Science 335, 545-546
   Abstract »    Full Text »    PDF »

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