Genomic and Transcriptomic Associations Identify a New Insecticide Resistance Phenotype for the Selective Sweep at the Cyp6g1 Locus of Drosophila melanogaster.
Scans of the Drosophila melanogaster genome have identified organophosphate resistance loci among those with the most pronounced signature of positive selection. In this study, the molecular basis of resistance to the organophosphate insecticide azinphos-methyl was investigated using the Drosophila Genetic Reference Panel, and genome-wide association. Recently released full transcriptome data were used to extend the utility of the Drosophila Genetic Reference Panel resource beyond traditional genome-wide association studies to allow systems genetics analyses of phenotypes. We found that both genomic and transcriptomic associations independently identified Cyp6g1, a gene involved in resistance to DDT and neonicotinoid insecticides, as the top candidate for azinphos-methyl resistance. This was verified by transgenically overexpressing Cyp6g1 using natural regulatory elements from a resistant allele, resulting in a 6.5-fold increase in resistance. We also identified four novel candidate genes associated with azinphos-methyl resistance, all of which are involved in either regulation of fat storage, or nervous system development. In Cyp6g1, we find a demonstrable resistance locus, a verification that transcriptome data can be used to identify variants associated with insecticide resistance, and an overlap between peaks of a genome-wide association study, and a genome-wide selective sweep analysis.
The Bio21 Institute and the School of Biosciences, The University of Melbourne, Parkville, Victoria 3010, Australia pbattlay@gmail.com.
Paul
0000-0001-6050-1868
P
Battlay
The Bio21 Institute and the School of Biosciences, The University of Melbourne, Parkville, Victoria 3010, Australia.
Joshua M
JM
Schmidt
The Bio21 Institute and the School of Biosciences, The University of Melbourne, Parkville, Victoria 3010, Australia.
Alexandre
A
Fournier-Level
The Bio21 Institute and the School of Biosciences, The University of Melbourne, Parkville, Victoria 3010, Australia.
Charles
0000-0002-7733-6763
C
Robin
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D001387:Azinphosmethyl / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics*; D049750:Genome, Insect; D055106:Genome-Wide Association Study; D007305:Insecticide Resistance / Q000235:genetics*; D010641:Phenotype; D059467:Transcriptome
D029721:Drosophila Proteins; D001387:Azinphosmethyl; D003577:Cytochrome P-450 Enzyme System; C446928:Cyp6g1 protein, Drosophila
Cyp6g1; D. melanogaster; Drosophila Genetic Reference Panel; azinphos-methyl; systems genetics