Methyl farnesoate (MF) plays hormonal regulatory roles in crustaceans. An epoxidated form of MF, known as juvenile hormone (JH), controls metamorphosis and stimulates reproduction in insects. To address the evolutionary significance of MF epoxidation, we generated mosquitoes completely lacking either of the two enzymes that catalyze the last steps of MF/JH biosynthesis and epoxidation, respectively: the JH acid methyltransferase (JHAMT) and the P450 epoxidase CYP15 (EPOX). jhamt^−/− larvae lacking both MF and JH died at the onset of metamorphosis. Strikingly, epox^−/− mutants, which synthesized MF but no JH, completed the entire life cycle. While epox^−/− adults were fertile, the reproductive performance of both sexes was dramatically reduced. Our results suggest that although MF can substitute for the absence of JH in mosquitoes, it is with a significant fitness cost. We propose that MF can fulfill most roles of JH, but its epoxidation to JH was a key innovation providing insects with a reproductive advantage.

法尼酸甲酯 (MF) 在甲壳类动物中发挥激素调节作用。MF 的一种环氧化形式，称为保幼激素 (JH)，可控制昆虫的变态并刺激昆虫的繁殖。为了解决 MF 环氧化的进化意义，我们产生的蚊子完全缺乏分别催化 MF/JH 生物合成和环氧化最后步骤的两种酶：JH 酸性甲基转移酶 (JHAMT) 和 P450 环氧酶 CYP15 (EPOX)。jhamt ^-/-缺乏 MF 和 JH 的幼虫在变态开始时死亡。引人注目的是，合成 MF 但不合成 JH 的epox ^-/-突变体完成了整个生命周期。而环氧树脂^-/-成年人有生育能力，两性的生殖能力都大大降低。我们的研究结果表明，虽然 MF 可以替代蚊子中 JH 的缺失，但它的适应性成本很高。我们认为 MF 可以发挥 JH 的大部分作用，但其对 JH 的环氧化是为昆虫提供繁殖优势的关键创新。