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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.)


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