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Science. 2012 Feb 3;335(6068):574-8. doi: 10.1126/science.1214318.

Natural variation in a chloride channel subunit confers avermectin resistance in C. elegans.

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1
Lewis-Sigler Institute for Integrative Genomics, Department of Ecology and Evolutionary Biology, and Howard Hughes Medical Institute, Princeton University, Princeton, NJ 08544, USA.

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.

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PMID:
22301316
PMCID:
PMC3273849
DOI:
10.1126/science.1214318
[Indexed for MEDLINE]
Free PMC Article

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