Molecular basis of genome interaction of the honeybee Apis mellifera with Nosema

我们以蜜蜂蜜蜂及其微孢子虫寄生虫Nosema为模型系统，研究了一种群居昆虫物种中寄主-寄生虫的共同进化。在之前的资助期间，我们可以将单个QTL定位到14号染色体上，该QTL降低了丹麦蜜蜂品系的寄主肠道中的寄生虫孢子负荷，该品系已被选为抗微孢子虫的品系。QTL是通过在相同的染色体区域进行选择性扫描而独立确认的，该区域只有四个开放阅读框。其中两个基因是抵抗微孢子虫感染的主要候选基因。一个基因是RNAi机制的一部分，另一个基因与昆虫先天免疫系统接触。在接下来的一段时间里，我们想要研究寄生虫基因组如何与宿主防御基因协商。我们将使用动物宿主和模型昆虫细胞培养系统作为宿主，利用人工进化实验来筛选两个不同微孢子虫物种的病原体基因组的选择模式。在抗性和感病蜜蜂品系以及细胞培养系统中，将根据毒力高低来选择微孢子虫。RNAi将被用来降低细胞培养系统的基因表达，以模拟在敏感宿主中的选择。利用感病基因和抗性基因杂合的杂交女王产生的靶标，我们将在寄主/病原菌转录组水平上筛选相互作用，并在人工选择高毒力和低毒力后，评估表型可塑性在病原菌毒力协同进化中的重要性。结果将突出寄生虫在毒力选择下表现出的遗传适应性程度，而不是毒力的表型可塑性。他们还将揭示介导微孢子虫毒力的共同遗传因素，并展示宿主-病原体系统共同进化的速度有多快。最后，研究结果还将告诉我们最初受寄主抗性选择影响的基因级联和生理途径，这可能指向保守的细胞防御机制。

We use the honeybee, Apis mellifera, and its Microsporidian parasite, Nosema as a model system to study host-parasite co-evolution in a social insect species. In the previous funding period, we could map a single QTL to chromosome 14 which reduced the parasite spore load in the host gut in a strain of Danish honeybees, which had been selected for Nosema resistance. The QTL was independently confirmed by a selective sweep in the identical chromosome region, comprising only four open reading frames. Two of these genes are prime candidates for resistance mechanisms against Nosema infections. One gene is part of the RNAi machinery and the other engages with the innate insect immune system. In the forthcoming period we want to study how the parasite genome negotiates with host defence genes.We will screen for patterns of selection in the pathogen genome in two different Nosema species using artificial evolution experiments, using both the animal host and a model insect cell culture system as host. Nosema will be selected for high and low virulence in the resistant and the susceptible honeybee strain and in the cell culture system. RNAi will be used to knock down gene expression of the cell culture system to mimic selection in a susceptible host. Using drones produced by a hybrid queen that is heterozygote for the susceptibility and the resistance allele, we will screen for interactions at the host/pathogen transcriptome level and also assess the importance of phenotypic plasticity in pathogen virulence for host-parasite co-evolution after artificial selection for high and low virulence. Results will highlight the degree of genetic adaptability the parasite can exhibit under selection for virulence, as opposed to phenotypic plasticity for virulence. They will also reveal common genetic factors that mediate Nosema virulence, and show how quickly host-pathogen systems can co-evolve. Finally, results will also inform us of the gene cascades and physiological pathways that have been affected by selection of host resistance in the first place, which could point to conserved cellular defence mechanisms.