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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)574-578
Number of pages5
JournalScience
Volume335
Issue number6068
DOIs
StatePublished - Feb 3 2012

ASJC Scopus subject areas

  • General

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