Data from: Loci contributing to boric acid toxicity in two reference populations of Drosophila melanogaster

Populations maintain considerable segregating variation in the response to toxic, xenobiotic compounds. To identify variants associated with resistance to boric acid, a commonly-used household insecticide with a poorly understood mechanism of action, we assayed thousands of individuals from hundreds of strains. Using the Drosophila Synthetic Population Resource (DSPR), a multi-parental population (MPP) of inbred genotypes, we mapped six QTL to short genomic regions containing few protein-coding genes (3–188), allowing us to identify plausible candidate genes underlying resistance to boric acid toxicity. One interval contains multiple genes from the cytochrome P450 family, and we show that ubiquitous RNAi of one of these genes, Cyp9b2, markedly reduces resistance to the toxin. Resistance to boric acid is positively correlated with caffeine resistance. The two phenotypes additionally share a pair of QTL, potentially suggesting a degree of pleiotropy in the genetic control of resistance to these two distinct xenobiotics. Finally, we screened the Drosophila Genetic Reference Panel (DGRP) in an attempt to identify sequence variants within mapped QTL that are associated with boric acid resistance. The approach was largely unsuccessful, with only one QTL showing any associations at QTL-specific 20% False Discovery Rate (FDR) thresholds. Nonetheless, these associations point to a potential candidate gene that can be targeted in future validation efforts. Although the mapping data resulting from the two reference populations do not clearly overlap, our work provides a starting point for further genetic dissection of the processes underlying boric acid toxicity in insects.

各类种群在应对有毒外源性化合物时，均维持着大量的分离遗传变异。为鉴定与硼酸抗性相关的遗传变异——硼酸是一种广泛使用的家用杀虫剂，其作用机制迄今尚未完全阐明——我们对数百个品系的数千个个体开展了检测。本研究借助果蝇合成种群资源（DSPR）——一类由近交基因型构建的多亲本种群（MPP）——将6个数量性状位点（QTL）定位到仅含3~188个蛋白质编码基因的短小基因组区域，由此得以挖掘介导硼酸毒性抗性的潜在候选基因。其中一个基因组区间内包含多个细胞色素P450家族基因，我们证实，对其中的Cyp9b2基因进行全身性RNA干扰（RNAi），可显著降低昆虫对该毒素的抗性。硼酸抗性与咖啡因抗性呈显著正相关，且这两种表型共享一对数量性状位点（QTL），这提示针对这两种不同外源性化合物的抗性遗传调控可能存在一定程度的基因多效性。最后，我们对果蝇遗传参考面板（DGRP）进行了筛选，以期在已定位的QTL区域内鉴定出与硼酸抗性相关的序列变异。该筛选策略整体收效甚微，仅1个QTL在QTL专属的20%错误发现率（FDR）阈值下呈现出显著关联信号。尽管如此，上述关联信号仍指向一个潜在的候选基因，可供后续验证研究使用。尽管两个参考种群得到的定位数据并未出现明确的重合，但本研究仍为进一步解析昆虫体内硼酸毒性的作用过程提供了重要起点。