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

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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.