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...

种群在对有毒外源性化合物的应答过程中，维持着显著的分离遗传变异。为鉴定与硼酸抗性相关的遗传变异——硼酸是一种常用家用杀虫剂，其作用机制尚未阐明——我们对数百个品系的数千个个体开展了检测分析。本研究利用果蝇合成种群资源（Drosophila Synthetic Population Resource, DSPR）——一种由近交基因型构建的多亲本种群（multi-parental population, MPP）——将6个数量性状位点（Quantitative Trait Locus, QTL）定位到了仅含3~188个蛋白编码基因的短小基因组区域中，由此得以鉴定出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基因进行泛在性RNA干扰，可显著降低果蝇对该毒素的抗性。硼酸抗性与咖啡因抗性呈正相关；此外，这两种表型共享一对数量性状位点，这提示两种抗性的遗传调控可能存在一定程度的多效性……