Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
ACS Chem Biol. 2012 Aug 17;7(8):1321-5. doi: 10.1021/cb300169c. Epub 2012 Jun 12.
In the model organism Caenorhabditis elegans, a class of small molecule signals called ascarosides regulate development, mating, and social behaviors. Ascaroside production has been studied in the predominant sex, the hermaphrodite, but not in males, which account for less than 1% of wild-type worms grown under typical laboratory conditions. Using HPLC-MS-based targeted metabolomics, we show that males also produce ascarosides and that their ascaroside profile differs markedly from that of hermaphrodites. Whereas hermaphrodite ascaroside profiles are dominated by ascr#3, containing an α,β-unsaturated fatty acid, males predominantly produce the corresponding dihydro-derivative ascr#10. This small structural modification profoundly affects signaling properties: hermaphrodites are retained by attomole-amounts of male-produced ascr#10, whereas hermaphrodite-produced ascr#3 repels hermaphrodites and attracts males. Male production of ascr#10 is population density-dependent, indicating sensory regulation of ascaroside biosynthesis. Analysis of gene expression data supports a model in which sex-specific regulation of peroxisomal β-oxidation produces functionally different ascaroside profiles.
在模式生物秀丽隐杆线虫中，一类称为ascarosides 的小分子信号调节发育、交配和社交行为。ascaroside 的产生已在主要性别——雌雄同体中进行了研究，但在雄性中尚未进行研究，而雄性在典型的实验室条件下生长的不到野生型蠕虫的 1%。使用基于 HPLC-MS 的靶向代谢组学，我们表明雄性也产生 ascarosides，并且它们的 ascaroside 图谱与雌雄同体明显不同。虽然雌雄同体 ascaroside 图谱主要由含有α,β-不饱和脂肪酸的 ascr#3 主导，但雄性主要产生相应的二氢衍生物 ascr#10。这种小的结构修饰极大地影响了信号转导特性：雄性产生的 attomole 数量的 ascr#10 可以保留雌雄同体，而雌雄同体产生的 ascr#3 则排斥雌雄同体并吸引雄性。雄性 ascr#10 的产生依赖于种群密度，表明对 ascaroside 生物合成的感觉调节。对基因表达数据的分析支持这样一种模型，即过氧化物酶体β-氧化的性别特异性调节产生功能不同的 ascaroside 图谱。
