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Saltational evolution of a pesticide-metabolizing cytochrome P450 in a global crop pest.

BACKGROUND
The cotton bollworm, Helicoverpa armigera (Hübner), is a damaging insect pest threatening agricultural crops worldwide due to its resistance to insecticides. Metabolic resistance to pyrethroid insecticides is conferred by the chimeric P450 enzyme CYP337B3, produced by unequal crossing-over between CYP337B1 and CYP337B2. CYP337B3 is 99.7% similar to CYP337B1 except for the 177 N-terminal amino acids containing the substrate recognition site 1 from CYP337B2. Here, we studied the structure-function relationship of CYP337B3 and CYP337B1 to determine the amino acids that enable CYP337B3 to efficiently hydroxylate the 4'-carbon position of fenvalerate, while neither CYP337B1 nor CYP337B2 can do so.


RESULTS
Site-directed mutagenesis showed the L114F substitution in CYP337B3 reduced its 4'-hydroxylation activity by 89%, but the reciprocal F114L substitution in CYP337B1 increased its 4'-hydroxylation activity to only 49% of the level of CYP337B3. Docking models showed that amino acid 114 seems to have different functions in CYP337B1 and CYP337B3. Antibodies detected 2 to 3-fold more CYP337B1 than CYP337B3 in larval cuticle, which along with a 49% 4'-hydroxylation activity increase due to a F114L substitution in vivo might be expected to provide as much protection of the larva against exposure to fenvalerate as CYP337B3. However, CYP337B3 is present at much higher frequencies than CYP337B1-CYP337B2 in most populations, including those recently invading South America.


CONCLUSION
The metabolic resistance to pyrethroids in H. armigera has evolved by saltational evolution; i.e. by a single mutation, an unequal crossing-over, producing a larger selective advantage than could be attained gradually by stepwise improvement of the parental enzyme. This article is protected by copyright. All rights reserved.