The diversity of Bt resistance genes in species of Lepidoptera.

Although the mode of action of Cry1A toxins produced by Bacillus thuringiensis is fairly well understood, knowledge of the molecular mechanisms by which lepidopteran species have evolved resistance to them is still in its infancy. The most common type of resistance has been called "Mode 1" and is characterized by recessive inheritance, >500-fold resistance to and reduced binding by at least one Cry1A toxin, and negligible cross-resistance to Cry1C. In three lepidopteran species, Heliothis virescens, Pectinophora gossypiella, and Helicoverpa armigera, Mode 1 resistance is caused by mutations in a toxin-binding 12-cadherin-domain protein expressed in the larval midgut. These mutations all interrupt the primary sequence of the protein and prevent its normal localization in the membrane, presumably removing a major toxic binding target of the Cry1A toxins. In Plutella xylostella, however, Mode 1 resistance appears to be caused by a different genetic mechanism, as Cry1A resistance is unlinked to the cadherin gene. Mapping studies in H. virescens have detected an additional major Cry1A resistance gene, which on the basis of comparative linkage mapping is distinct from the one in P. xylostella. An additional resistance mechanism supported by genetic data involves a protoxin-processing protease in Plodia interpunctella, and this is likely to be different from the genes mapped in Plutella and Heliothis. Thus, resistance to Cry1A toxins in species of Lepidoptera has a complex genetic basis, with at least four distinct, major resistance genes of which three are mapped in one or more species. The connection between resistance genes and the mechanisms they encode remains a challenging task to elucidate.