Wilson Thomas G, Wang Shaoli, Beno Milan, Farkas Robert
Department of Entomology, Ohio State University, Columbus, OH 43210, USA.
Mol Genet Genomics. 2006 Sep;276(3):294-303. doi: 10.1007/s00438-006-0138-4. Epub 2006 Jun 27.
The Methoprene-tolerant (Met) bHLH-PAS gene in Drosophila melanogaster is involved in the molecular action of juvenile hormone (JH), and mutants result in resistance to the toxic and morphogenetic effects of JH and JH agonist insecticides such as methoprene. A detailed study of Met mutants can shed light on the poorly understood action of JH as well as the molecular basis of Met resistance to JH insecticides. Nine mutant alleles bearing point mutations in Met were examined for penetrance and expressivity of three phenotypic characters: resistance, defective oogenesis, and a novel eye defect. The collection ranged from two weak alleles having less severe phenotypes to strong alleles with severe phenotypes similar to that of a null allele. The point mutations were located in both conserved and nonconserved domains. Both the eye defect, seen as severely malformed ommatidial facets in the posterior margin of the compound eye, and the oogenesis phenotype are nonconditional, whereas expression of the resistance phenotype requires treatment with JH or JH analogs (JHAs) during early metamorphosis. A proposed basis for all the phenotypic characters centers on MET action as a transcriptional regulator of ecdysone secondary-response target genes during metamorphosis. Disruption of MET function either by mutation or by JHA presence during early metamorphosis results in transcriptional misregulation of different target genes, resulting in the pathology seen in either instance. The variety of amino acid changes in MET that resulted in resistance may portend a rapid rise in resistance in response to increased use of JH insecticides in field insect populations.
黑腹果蝇中耐甲氧普烯（Met）的bHLH - PAS基因参与保幼激素（JH）的分子作用，该基因的突变体对JH以及甲氧普烯等JH激动剂杀虫剂的毒性和形态发生效应具有抗性。对Met突变体进行详细研究，有助于深入了解人们知之甚少的JH作用以及Met对JH杀虫剂产生抗性的分子基础。研究人员检测了9个在Met中携带点突变的突变等位基因，观察其在三种表型特征上的外显率和表现度，这三种表型特征分别为：抗性、卵子发生缺陷和一种新发现的眼部缺陷。这些突变等位基因涵盖了从表型不太严重的两个弱等位基因到与无效等位基因表型相似的严重等位基因。点突变位于保守结构域和非保守结构域。眼部缺陷表现为复眼后缘小眼面严重畸形，卵子发生表型均为非条件性的，而抗性表型的表达需要在变态初期用JH或JH类似物（JHA）进行处理。所有表型特征的一个推测基础是，在变态过程中，MET作为蜕皮激素二级反应靶基因的转录调节因子发挥作用。在变态初期，无论是通过突变还是JHA的存在破坏MET功能，都会导致不同靶基因的转录失调，从而在这两种情况下出现病理现象。MET中导致抗性的多种氨基酸变化可能预示着随着田间昆虫种群中JH杀虫剂使用量的增加，抗性将迅速上升。
