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 γ-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.