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

研究长寿、抗病和行为等复杂特征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。果蝇幼虫的觅食在很大程度上受觅食基因（for）的天然等位基因变异的影响。这些等位基因赋予了一种自然的行为多态性，使得漫游者（forR）和坐着者（fors）在食物斑块之间和食物斑块内的移动速度不同。新的初步证据表明，觅食行为也受到修饰基因翅上a （wupA）的自然等位基因变异的影响。wupA将漫游车的觅食行为降低到保姆的水平。在哺乳动物中，由for编码的cgmp依赖性蛋白激酶可磷酸化由wupA编码的肌钙蛋白i （TnI）蛋白。TnI是肌肉收缩的重要调节因子，可能与寻找食物行为的肌肉输出有关。我建议进一步研究wupA和for之间上位相互作用的作用，首先使用数量性状位点定位和wupA和for突变体的互补测试来确认wupA的行为作用。我将通过渗入wupA和for的等位基因来测量for和wupA的自然等位基因变异的相对行为含义。鉴于之前的分析已经显示了负频率依赖选择在维持等位基因变异中的作用，我将研究wupA的变异是否在维持漫游者和坐者中起作用。最后，我建议通过从12个果蝇物种的基因组序列中寻找for和wupA配对的正选择特征，开始评估for/wupA等位基因的群体遗传学和分子进化。然后，我将把这些分析扩展到最近从一个自然种群中衍生出来的一系列近交系。了解蚁群与wupA对觅食行为的动态上位相互作用，为研究复杂性状进化提供了独特的途径和模型体系。

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.