Cyclodiene insecticide resistance: From molecular to population genetics

This review follows progress in the analysis of cyclodiene insecticide resi stance from the initial isolation of the mutant, through cloning of the res istance gene, to an examination of the distribution of resistance alleles i n natural populations. Emphasis is given to the use of a resistant Drosophi la mutant as an entry point to cloning the associated gamma-aminobutyric ac id (GABA) receptor subunit gene, Resistance to dieldrin. Resistance is asso ciated with replacements of a single amino acid (alanine302) in the chlorid e ion channel pore of the protein. Replacements of alanine302 not only dire ctly affect the drug binding site but also allosterically destabilize the d rug preferred conformation of the receptor. Resistance is thus conferred by a unique dual mechanism associated with alanine302, which is the only resi due replaced in a wide range of different resistant insects. The underlying mutations appear either to have arisen once, or multiply, depending on the population biology of the pest insect. Although resistance frequencies dec line in the absence of selection, resistance alleles can persist at relativ ely high frequency and may cause problems for compounds to which cross-resi stance is observed, such as the novel fipronils.