Why are there so few resistance-associated mutations in insecticide target genes?

The genes encoding the three major targets of conventional insecticides are: Rdl, which encodes a gamma-aminobutyric acid receptor subunit (RDL); para, which encodes a voltage-gated sodium channel (PARA); and Ace, which encodes insect acetylcholinesterase (AChE). Interestingly, despite the complexity of the encoded receptors or enzymes, very few amino acid residues are replaced in different resistant insects: one within RDL, two within PARA and three or more within AChE. Here we examine the possible reasons underlying this extreme conservation by looking at the aspects of receptor and/or enzyme function that may constrain replacements to such a limited number of residues.