The Drosophila foraging gene: gene regulation, pleiotropy and plasticity

果蝇觅食基因：基因调控、多效性和可塑性

• 批准号: RGPIN-2022-04346
• 负责人: Sokolowski, MarlaB
• 金额: $ 5.83万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=751457
• 关键词: Drosophila; foraging; gene; regulation; pleiotropy

Geneticists traditionally study a single well-defined function associated with a gene. However, many genes have multiple functions (pleiotropy) in different tissues and sometimes even within the same tissue. This proposal investigates how different parts of a gene support different functions, from a gene regulation perspective. We hypothesize that the foraging gene's modular structure and complexity facilitates its multiple functions. We use the fruit fly Drosophila melanogaster with its unsurpassed genetic tool kit. Our efforts are focused on the Drosophila foraging gene that encodes a signalling molecule called cGMP dependent protein kinase. The foraging gene encodes two natural allelic variants called rover and sitter. While foraging, rover flies move more and find more food than sitters. The foraging gene has many functions; in addition to foraging behaviour it modulates learning and memory, sleep, stress responses and social behaviours. In the present grant, we address how, from a molecular perspective, foraging accomplishes its pleiotropic functions in Drosophila social behaviours.  Social behaviours to be studied are: 1) Larval social foraging: Larval social foraging occurs under high-density conditions when 3rd instar larvae form groups who synchronize their downward digging into the liquified food. Under low-density rearing both sitters and rovers forage alone (solitary foraging) whereas under high density, sitters forage in groups (social foraging) while rovers (and larvae with the foraging gene genetically deleted) forage alone. 2) Adult social interaction duration: In groups, adult sitter flies have significantly longer interaction durations than rovers. Social isolation reduces the interaction duration of sitters but not rovers. Genetic analyses tie a number of adult social phenotypes to the foraging gene. The foraging gene is a complex gene comprising about 35kb of DNA. The foraging gene produces many gene products including 21 transcripts an approximately 9 protien isoforms.  The foraging gene is conserved across species and found in multiple systems, tissues and cells throughout development and adulthood of the fly. In the current proposal our objectives are to investigate 1) how the foraging gene's complex structure (multiple promoters, RNA transcripts and protein isoforms) play a modular role in Drosophila social behaviours and, 2) how social behaviours are regulated by interactions between the foraging gene and its epigenetic regulators (G9a, a histone methyl transferase gene, and the microRNA, miR-932), and how the social environment (e.g. social isolation) acts to change these patterns of regulation. This research will build a comprehensive and foundational understanding of how a complex gene affects multiple interacting phenotypes to generate normal individual differences in social behaviour.

传统上，遗传学家研究了与基因相关的单个定义明确的功能。但是，许多基因在不同组织中，有时甚至在同一组织中具有多种功能（多效性）。该建议从基因调节的角度研究了基因的不同部分如何支持不同的功能。我们假设觅食基因的模块化结构和复杂性设施其多个功能。我们将果蝇果蝇Melanogaster与其无与伦比的遗传工具套件一起使用。我们的努力集中在编码一个称为CGMP依赖性蛋白激酶的信号分子的果蝇觅食基因上。觅食基因编码两个自然等位基因变体，称为Rover and Natter。在觅食时，漫游者苍蝇移动更多，比保姆更多的食物。觅食基因具有许多功能。除了觅食行为外，它可以调节学习和记忆，睡眠，压力反应和社交行为。在目前的赠款中，我们从分子的角度解决了如何在果蝇社会行为中实现其多效性功能。要研究的社会行为是：1）幼虫社会觅食：幼体社会觅食发生在高密度条件下，当3龄幼虫形成群体组成的群体同步他们向下挖掘到清算食品中。在低密度饲养的情况下，保姆和流浪者的觅食（孤立的觅食），而在高密度下，保姆分成组（社会觅食），而流浪者（和带有觅食基因的幼虫通常被删除的觅食）。 2）成人社会互动持续时间：在组中，成年保姆苍蝇的相互作用持续时间明显比流浪者更长。社会隔离会减少保姆的相互作用持续时间，但不能减少流浪者。遗传分析将许多成人社会表型与觅食基因联系起来。觅食基因是一个完成约35kb DNA的复杂基因。觅食基因产生许多基因产物，包括21种转录本大约9个蛋白质同工型。觅食基因在整个物种之间是保守的，并且在整个苍蝇的发育和成年期间都发现了多个系统，组织和细胞。 In the current proposals are to investigate 1) how the foraging gene's complex structure (multiple promoters, RNA transcripts and protein isoforms) play a modular role in Drosophila social behaviors and, 2) how social behaviors are regulated by interactions between the foraging gene and its epigenetic regulators (G9a, a histone methyl transfer gene, and the microRNA, miR-932), and how the social environment （例如，社会隔离）采取行动改变了这些监管模式。这项研究将建立对复杂基因如何影响多种相互作用表型的全面和基本的理解，以产生社会行为的正常个体差异。