title: Mutations in Dalpha1 or Dbeta2 nicotinic acetylcholine receptor subunits can confer resistance to neonicotinoids in Drosophila melanogaster.
abstract: Resistance to insecticides by modification of their molecular targets is a serious problem in chemical control of many arthropod pests. Neonicotinoids target the nicotinic acetylcholine receptor (nAChR) of arthropods. The spectrum of possible resistance-conferring mutations of this receptor is poorly understood. Prediction of resistance is complicated by the existence of multiple genes encoding the different subunits of this essential component of neurotransmission. We focused on the cluster of three Drosophila melanogaster nAChR subunit genes at cytological region 96A. EMS mutagenesis and selection for resistance to nitenpyram was performed on hybrids carrying a deficiency for this chromosomal region. Two complementation groups were defined for the four strains isolated. Molecular characterisation of the mutations found lesions in two nAChR subunit genes, Dalpha1 (encoding an alpha-type subunit) and Dbeta2 (beta-type). Mutations conferring resistance in beta-type receptors have not previously been reported, but we found several lesions in the Dbeta2 sequence, including locations distant from the predicted neonicotinoid-binding site. This study illustrates that mutations in a single-receptor subunit can confer nitenpyram resistance. Moreover, some of the mutations may protect the insect against nitenpyram by interfering with subunit assembly or channel activation, rather than affecting binding affinities of neonicotinoids to the channel.
authors.affiliation: Centre for Environmental Stress and Adaptation Research, Department of Genetics, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3052, Australia. trentp@unimelb.edu.au
authors.forename: Trent
authors.initials: T
authors.lastname: Perry
authors.forename: David G
authors.initials: DG
authors.lastname: Heckel
authors.forename: John A
authors.initials: JA
authors.lastname: McKenzie
authors.forename: Philip
authors.initials: P
authors.lastname: Batterham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005816:Genetic Complementation Test; D040582:Inheritance Patterns; D007305:Insecticide Resistance / Q000235:genetics; D007306:Insecticides; D008297:Male; D008969:Molecular Sequence Data; D000073943:Neonicotinoids; D011725:Pyridines; D011978:Receptors, Nicotinic / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D007306:Insecticides; D000073943:Neonicotinoids; D011725:Pyridines; D011978:Receptors, Nicotinic; C114279:nAChRalpha1 protein, Drosophila; C464843:nitenpyram