Genetic analyses of allelic variation in cGMP-dependent protein kinase and troponin-1 and their effects on behaviour

cGMP 依赖性蛋白激酶和肌钙蛋白-1 等位基因变异的遗传分析及其对行为的影响

• 批准号: 371554-2009
• 负责人: Fitzpatrick, Mark
• 金额: $ 3.35万
• 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: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=483622
• 关键词: Genetic; analyses; allelic; variation; cGMP

Investigating the genetic basis of complex traits like longevity, disease resistance, and behaviour is challenging since they are influenced by numerous genes and by fluctuations in the environment. The lability and complexity of behaviours like foraging are ideal for investigating the evolutionary genetics of complex traits. Foraging in larval fruit flies, Drosophila melanogaster, is largely influenced by natural allelic variation in the foraging gene (for). These alleles confer a natural behaviour polymorphism where rovers (forR) and sitters (fors) differ in their movement rates between and within food patches. New preliminary evidence suggests that foraging behaviour is also influenced by natural allelic variation in a modifier gene wings up A (wupA). wupA decreases rover foraging behaviour to a sitter level. In mammals the cGMP-dependent protein kinase, encoded by for, phosphorylates the Troponin-I (TnI) protein encoded by wupA. TnI is an important regulator of muscle contraction and is likely involved in the muscle output of food search behaviours. I propose to further investigate the role of epistatic interactions between wupA and for by first confirming a behavioural role for wupA using quantitative trait locus mapping and complementation tests with mutants in both wupA and for. I will measure the relative behavioural implications of natural allelic variation in for and wupA by introgressing alleles of wupA and for. Given that previous analyses have shown a role for negative frequency-dependent selection in maintaining allelic variation in for, I will investigate whether variation in wupA plays a role in the maintenance rovers and sitters. Finally, I propose to begin assessing the population genetics and molecular evolution of alleles in for/wupA by looking for signatures of positive selection in alignments of for and wupA from the genome sequences of 12 Drosophila species. I will then extend these analyses to a series of inbred lines that were recently derived from a natural population. Understanding the dynamic epistatic interactions between for and wupA on foraging behaviour provides a unique avenue and model system for studying complex trait evolution.

研究长寿、抗病和行为等复杂性状的遗传基础具有挑战性，因为它们受到众多基因和环境波动的影响。觅食等行为的不稳定性和复杂性是研究复杂性状的进化遗传学的理想选择。觅食的幼虫果蝇，果蝇，在很大程度上是由自然的等位基因变异觅食基因（为）。这些等位基因赋予了一个自然的行为多态性，其中漫游者（forR）和坐者（fors）在食物斑块之间和食物斑块内的运动速率不同。新的初步证据表明，觅食行为也受到修饰基因wings up A（wupA）中自然等位基因变异的影响。wupA降低漫游者觅食行为的坐在一个水平。在哺乳动物中，由for编码的cGMP依赖性蛋白激酶磷酸化由wupA编码的肌钙蛋白-I（TnI）蛋白。肌钙蛋白I是肌肉收缩的重要调节剂，可能参与食物搜索行为的肌肉输出。我建议进一步研究wupA和for之间上位性相互作用的作用，首先使用数量性状基因座作图和wupA和for突变体的互补测试来确认wupA的行为作用。我将测量的相对行为的影响，自然等位基因变异的wupA和wupA基因渐渗的等位基因。鉴于以前的分析表明，负频率依赖性选择在维持等位基因变异的作用，我将调查是否在wupA的变化发挥了作用，在维护漫游者和坐。最后，我建议开始评估的群体遗传学和等位基因的分子进化的for/wupA的12个果蝇物种的基因组序列的比对中寻找正选择的签名。然后，我将把这些分析扩展到最近从自然种群中获得的一系列近交系。了解动态上位性之间的相互作用和wupA觅食行为提供了一个独特的途径和模型系统，研究复杂的性状进化。