乙酰肉碱参与飞蝗两型转变调控的表观遗传机制研究

Phase change in the migratory locust is a key step for outbreaks of locust plagues and a ideal study model for phenotypic plasticity. We have demonstrated that acetyl-carnitine can have important roles in behavioral plasticity during phase change through metabolomic analysis. However, the detailed mechanisms underlying the regulation of acetyl-carnitine on locust phase change have been unknown now. According to the results from other animals, we suppose here that behavioral function of acetyl-carnitine on phase change may be through influencing the state of histone acetylation in central nervous system. In this project, we will conduct the integrative studies including genomics, ethology, neuronscience and gene interference to verify this hypothesis. We will investigate the effects of acetyl-carnitine on histone acetylation in central nervous system of locusts, define the molecular targets of histone acetylation by acetylcarnitine and investigate whether acetylcarnitine regulates genes and pathways which are influenced by histone acetylation. We will identify which genes and pathways can have roles in behavoiral change during phase change.

飞蝗两型转变是蝗灾暴发的生物学基础，也是表型可塑性研究的重要模式。我们前期研究通过代谢组学分析已经证明乙酰肉碱能够参与飞蝗型变过程中行为可塑性的调控。但其具体机制还需进一步明确。我们提出乙酰肉碱可能通过影响组蛋白乙酰化表观遗传修饰来发挥作用的假设。本项目中，我们拟结合基因组学、行为学、神经生物学和基因操作技术，来验证这一假设。通过回答乙酰肉碱是否能够影响飞蝗组蛋白乙酰化状态、神经组织中由乙酰肉碱引起的组蛋白乙酰化程度改变的分子靶标是什么、哪些乙酰肉碱调控的下游分子途径引起神经和行为的效应等问题来阐释乙酰肉碱调控行为可塑性的具体机制。

飞蝗两型转变是蝗灾暴发的生物学基础，也是表型可塑性研究的重要模式。基于任务书的内容，本项目顺利完成预订目标并进行了适度拓展。我们基于基因组和转录组数据库，全面系统地鉴定了飞蝗中存在的组蛋白乙酰化及甲基化相关酶类的同源物。通过鉴定工作，我们证明飞蝗包含有几乎所有在节肢类动物中报道过的组蛋白乙酰化及甲基化相关酶类的类型。此外，我们通过系统发育和祖先状态重建分析揭示了一种名为SmydA的节肢动物特异性SET基因家族。荧光原位杂交实验和体外甲基转移酶活性分析表明SmydA-2基因是具有转录活性并且保留了原始的组蛋白甲基转移酶的活性。另外，我们揭示了两个同源的神经肽F：NPF1a及NPF2，通过抑制一氧化氮信号通路调控飞蝗型变过程中的运动可塑性。这些工作揭示组蛋白乙酰化表观遗传修饰、不同神经肽与飞蝗两性转变的调节机制，为蝗灾治理的药物靶标分子筛选提供了可选目标。本项目共发表SCI论文8篇。培养博士后1名，博士生2名，硕士研究生3名。