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

本文以蜜蜂及其微孢子虫小孢子虫为模型系统，研究了一种群居昆虫的宿主-寄生虫协同进化。在之前的资助期内，我们可以将单个QTL定位到14号染色体上，该染色体减少了被选为小虫病抗性的丹麦蜜蜂菌株的宿主肠道中的寄生虫孢子负荷。该QTL通过对仅包含4个开放阅读框的同染色体区域的选择性扫描独立确认。其中两个基因是针对小虫感染的耐药机制的主要候选基因。一个基因是RNAi机制的一部分，另一个基因与昆虫的先天免疫系统有关。在即将到来的时期，我们想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式昆虫细胞培养系统作为宿主，使用人工进化实验筛选两种不同小虫物种病原体基因组的选择模式。在抗性和易感蜜蜂品系和细胞培养系统中，将根据高毒力和低毒力选择小虫。RNAi将用于敲低细胞培养系统的基因表达，以模拟易感宿主的选择。我们将利用由易感等位基因和抗性等位基因杂合子杂交后产生的雄蜂，筛选宿主/病原体转录组水平上的相互作用，并在人工选择高毒力和低毒力后，评估表型可塑性在病原体毒力中对宿主-寄生虫共同进化的重要性。结果将强调寄生虫在毒力选择下可以表现出的遗传适应性程度，而不是毒力的表型可塑性。他们还将揭示介导小孢子虫毒力的共同遗传因素，并显示宿主-病原体系统共同进化的速度有多快。最后，结果还将告诉我们基因级联和生理途径，这些途径首先受到宿主抗性选择的影响，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.