Comparative Analysis of the Molecular Mechanisms of Ageing in Flies and Bees

生命史理论和衰老进化的一个核心部分是生育能力/寿命的权衡。社会性昆虫代表了一个令人困惑的例子，在这种情况下，在动物中普遍存在的权衡是相反的：繁殖个体是最长寿的个体。有趣的是，支撑这种权衡的生理途径和激素参与者大体上是保守的。然而，在群居昆虫中，我们缺乏对如何以及哪些保守途径或特定基因被增选以展示新功能的全面理解，以及哪些新的调节网络和基因促进了繁殖力/寿命权衡的逆转。本研究旨在探讨候选基因和关键基因在繁殖力/长寿表型中的功能作用和调控分子联系。为此，我们建立在与繁殖力和寿命相关的基因表达谱的广泛经验见解的基础上（研究单位的第一个资助阶段）。这些结果支持了TOR-Insulin-JuvenileHormone/Vitellogenin通路（TI-J-LiFe）的主要作用，并进一步揭示了几种或特定于单一社会物种的新候选基因。我们将通过沉默（RNAi）候选基因在社会性昆虫（蜜蜂）和非社会性昆虫（果蝇）中的表达来功能性测试候选基因的表型影响，以解决以下问题：哪些基因和基因级联是群居昆虫寿命和/或繁殖力的主要调节因子？2)候选基因具有哪些分子连接/它们是哪些途径的一部分？3)候选基因/途径/网络在社会性昆虫和苍蝇中是否具有相同的进化保守效应和联系？我们采用非社会性昆虫和社会性昆虫的比较方法，提供了检测调节繁殖力/寿命权衡的进化保守机制的能力，并使我们能够发现社会性昆虫特有的新特性。除了bbbb30候选基因的表型影响外，我们还将通过分析共表达网络（RNAseq）来确定这些基因的分子互联性，揭示它们在支持繁殖力和/或寿命的基因调控网络中的功能证据。特别是，这将提供关于哪些基因是连接不同途径的中心枢纽的见解，无论是以保守的还是以进化的新颖的，社会性昆虫特有的方式。我们的项目是迄今为止对群居昆虫繁殖力和寿命的分子调控进行的最全面的功能研究，特别是将揭示繁殖力和寿命与社会性之间权衡的逆转。

A central part of the life history theory and the evolution of ageing is the fecundity/longevity trade-off. Eusocial insects represent a puzzling case in which this otherwise in animals universal trade-off is reversed: the reproductive individuals are the longest lived individuals. Interestingly, the physiological pathways and hormonal players underpinning the trade-off are broadly conserved. However, in social insects we lack a comprehensive understanding on how and which conserved pathways or specific genes were co-opted to exhibit novel functions, and which novel regulatory networks and genes facilitated the reversal of the fedundity/longevity trade-off.This proposal aims to investigate the functional roles and regulatory molecular connections of candidate genes and key players implicated in the fecundity/longevity phenotype. For this, we build on the extensive empiricial insights on gene expression profiles related to fecundity and longevity (1st funding phase of the Research Unit). These results support a major role of the TOR-Insulin-JuvenileHormone/Vitellogenin pathways (TI-J-LiFe), and additionally revealed new candidate genes common for several or specific to single social species. We will functionally test the phenotypic impact of candidate genes by silencing (RNAi) their expression in a social (honeybee) and a non-social (fruitfly) insect to address the following questions:1. Which genes and gene cascades are major regulators of social insect longevity and/or fecundity?2) Which molecular connections do candidate genes possess/ which pathways are they part of?3) Do candidate genes/pathways/networks have the same evolutionary conserved effects and connections in social insects and the fly?Our comparative approach using a non-social and a social insect provides the power to detect evolutionary conserved mechanisms regulating the fecundity/longevity trade-off and enables us to discover novelties specific to social insects. In addition to phenotypic impact of >30 candidate genes, we will determine the molecular interconnectivities of these genes by analysing co-expression networks (RNAseq), revealing functional evidence for their position in gene regulatory networks underpinning fecundity and/or longevity. In particular, this will provide insights on which genes are central hubs connecting different pathways either in a conserved or in an evolutionary novel, social insect-specific manner. Our project is the thus far most comprehensive functional investigation into the molecular regulation of fecundity and longevity in social insects in general, and will, in particular, shed light on the reversal of the trade-off between fecundity and longevity with sociality.