RNA interference (RNAi) plays a key role in insect defense against viruses and transposable elements, and it is being applied as an experimental tool and for insect pest control. However, RNAi efficiency is highly variable for some insects, notably the pea aphid Acyrthosiphon pisum. In this study, we used natural variation in RNAi susceptibility of pea aphids to identify genes that influence RNAi efficiency. Susceptibility to orally-delivered dsRNA against the gut aquaporin gene AQP1 (ds-AQP1) varied widely across a panel of 83 pea aphid genotypes, from zero to total mortality. Genome-wide association between aphid performance on ds-AQP1 supplemented diet and aphid genetic variants yielded 103 significantly associated single nucleotide polymorphisms (SNPs), including variants in 55 genes, at the 10⁻⁴ probability cut-off. When ds-AQP1 was co-administered with dsRNA against six candidate genes, aphid mortality was reduced for three (50%) genes: the orthologs of the Drosophila genes trachealess (CG42865), headcase (CG15532) and a gene coding a peritrophin-A domain (CG8192), indicating that these genes function to promote RNAi efficiency against AQP1 in the pea aphid. Aphid susceptibility (quantified as mortality) to ds-AQP1 was correlated with RNAi against a further gene, snakeskin with essential gut function unrelated to AQP1, for some but not all aphid genotypes tested, suggesting that the determinants of RNAi efficiency may be partly gene-specific. This study demonstrates high levels of natural variation in susceptibility to RNAi and demonstrates the value of harnessing this variation to identify genes influencing RNAi efficiency.

RNA干扰（RNAi）在昆虫防御病毒和转座因子中起着关键作用，它已被用作实验工具和控制害虫。但是，RNAi效率对于某些昆虫（尤其是豌豆蚜虫Acyrthosiphon pisum）具有很大的可变性。在这项研究中，我们利用豌豆蚜虫对RNAi敏感性的自然变异来鉴定影响RNAi效率的基因。对肠道水通道蛋白基因AQP1（ds- AQP1）口服dsRNA的易感性在83种豌豆蚜虫基因型中有很大差异，从零到总死亡率。ds- AQP1上蚜虫性能之间的全基因组关联补充饮食和蚜虫的遗传变异产生了103个显着相关的单核苷酸多态性（SNP），包括55个基因的变异，截止概率为10 ^-4。当针对六个候选基因将ds- AQP1与dsRNA共同施用时，蚜虫死亡率降低了三个（50％）基因：果蝇无气管（CG42865），头套（CG15532）和果糖蛋白A编码基因的直系同源基因。域（CG8192），表明这些基因的功能是提高豌豆蚜虫对AQP1的RNAi效率。ds- AQP1对蚜虫的敏感性（量化为死亡率）与针对另一个基因的RNAi相关，对于某些但不是全部的蚜虫基因型，具有基本肠功能的蛇皮与AQP1无关，这表明RNAi效率的决定因素可能部分是基因特异性的。这项研究证明了对RNAi敏感性的高水平自然变异，并证明了利用这种变异来鉴定影响RNAi效率的基因的价值。