TY - JOUR
T1 - Point mutations in the Drosophila sodium channel gene para associated with resistance to DDT and pyrethroid insecticides
AU - Pittendrigh, B.
AU - Reenan, R.
AU - Ffrench-Constant, R. H.
AU - Ganetzky, B.
N1 - Funding Information:
Acknowledgements We thank R. Kreber for technical assistance. Supported by PHS Grants to GM43100 to B.G and NS29623 to R. ff-C. This is paper 3493 from the Laboratory of Genetics, University of Wisconsin-Madison.
PY - 1997
Y1 - 1997
N2 - The gene para in Drosophila melanogaster encodes an α subunit of voltage-activated sodium channels, the presumed site of action of DDT and pyrethroid insecticides. We used an existing collection of Drosophila para mutants to examine the molecular basis of target-site resistance to pyrethroids and DDT. Six out of thirteen mutants rested were associated with a largely dominant, 10- to 30-fold increase in DDT resistance. The amino acid lesions associated with these alleles defined four sites in the sodium channel polypeptide where a mutational change can cause resistance: within the intracellular loop between S4 and S5 in homology domains I and III, within the pore region of homology domain III, and within S6 in homology domain III. Some of these sites are analogous with those defined by knockdown resistance (kdr) and super-kdr resistance-associated mutations in houseflies and other insects, but are located in different homologous units of the channel polypeptide. We find a striking synergism in resistance levels with particular heterozygous combinations of para alleles that appears to mimic the super-kdr double mutant housefly phenotype. Our results indicate that the alleles analyzed from natural populations represent only a subset of mutations that can confer resistance. The implications for the binding site of pyrethroids and mechanisms of target-site insensitivity are discussed.
AB - The gene para in Drosophila melanogaster encodes an α subunit of voltage-activated sodium channels, the presumed site of action of DDT and pyrethroid insecticides. We used an existing collection of Drosophila para mutants to examine the molecular basis of target-site resistance to pyrethroids and DDT. Six out of thirteen mutants rested were associated with a largely dominant, 10- to 30-fold increase in DDT resistance. The amino acid lesions associated with these alleles defined four sites in the sodium channel polypeptide where a mutational change can cause resistance: within the intracellular loop between S4 and S5 in homology domains I and III, within the pore region of homology domain III, and within S6 in homology domain III. Some of these sites are analogous with those defined by knockdown resistance (kdr) and super-kdr resistance-associated mutations in houseflies and other insects, but are located in different homologous units of the channel polypeptide. We find a striking synergism in resistance levels with particular heterozygous combinations of para alleles that appears to mimic the super-kdr double mutant housefly phenotype. Our results indicate that the alleles analyzed from natural populations represent only a subset of mutations that can confer resistance. The implications for the binding site of pyrethroids and mechanisms of target-site insensitivity are discussed.
KW - DDT/pyrethroids
KW - Drosophila melanogaster
KW - Insecticide resistance
KW - Voltage-gated sodium channel
KW - para
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U2 - 10.1007/s004380050608
DO - 10.1007/s004380050608
M3 - Article
C2 - 9435785
AN - SCOPUS:0030661627
VL - 256
SP - 602
EP - 610
JO - Zeitschrift für Induktive Abstammungs- und Vererbungslehre
JF - Zeitschrift für Induktive Abstammungs- und Vererbungslehre
SN - 1617-4615
IS - 6
ER -