Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing.
Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing.
复制标题
DOI：
10.1101/gr.189225.115
复制
发表时间：
2015-09
期刊：
影响因子：
7
通讯作者：
David JP
中科院分区：
文献类型：
--
作者：
Faucon F;Dusfour I;Gaude T;Navratil V;Boyer F;Chandre F;Sirisopa P;Thanispong K;Juntarajumnong W;Poupardin R;Chareonviriyaphap T;Girod R;Corbel V;Reynaud S;David JP
蚊子抵抗杀虫剂的能力威胁到登革热和疟疾等疾病的控制。在实施替代控制工具之前，表征抗性机制对于管理自然种群中的抗性至关重要。通过解毒酶进行的杀虫剂生物降解是一种常见的耐药机制;然而，这种机制背后的基因组变化很少被确定，排除了个体耐药基因分型。特别是，解毒酶的拷贝数变异（CNVs）和多态性的作用从未在基因组水平上进行过研究，尽管它们可以代表代谢抗性的强大标记。在这种情况下，我们结合目标富集与高通量测序进行第一次全面筛选的基因扩增和多态性与杀虫剂抗性蚊子。在登革热蚊子Ae的几个种群中捕获并深度测序了760多个候选基因。埃及伊蚊显示出不同的遗传背景和对杀虫剂溴氰菊酯的不同抗性水平。CNV分析确定了41个与抗性相关的基因扩增，其中大部分影响抗性种群中细胞色素P450的过度转录。多态性分析在特定基因组区域检测到超过30，000个变体和强选择足迹。结合贝叶斯和等位基因频率过滤方法，确定了55个非同义变异与耐药性密切相关。CNVs和多态性在区域内是保守的，但在各大洲之间是不同的，这证实了对杀虫剂的代谢抗性的基因组变化并不普遍。通过鉴定杀虫剂抗性的新DNA标记，这项研究为追踪蚊子在种群内和种群间抵抗杀虫剂而产生的代谢变化开辟了道路。
The capacity of mosquitoes to resist insecticides threatens the control of diseases such as dengue and malaria. Until alternative control tools are implemented, characterizing resistance mechanisms is crucial for managing resistance in natural populations. Insecticide biodegradation by detoxification enzymes is a common resistance mechanism; however, the genomic changes underlying this mechanism have rarely been identified, precluding individual resistance genotyping. In particular, the role of copy number variations (CNVs) and polymorphisms of detoxification enzymes have never been investigated at the genome level, although they can represent robust markers of metabolic resistance. In this context, we combined target enrichment with high-throughput sequencing for conducting the first comprehensive screening of gene amplifications and polymorphisms associated with insecticide resistance in mosquitoes. More than 760 candidate genes were captured and deep sequenced in several populations of the dengue mosquito Ae. aegypti displaying distinct genetic backgrounds and contrasted resistance levels to the insecticide deltamethrin. CNV analysis identified 41 gene amplifications associated with resistance, most affecting cytochrome P450s overtranscribed in resistant populations. Polymorphism analysis detected more than 30,000 variants and strong selection footprints in specific genomic regions. Combining Bayesian and allele frequency filtering approaches identified 55 nonsynonymous variants strongly associated with resistance. Both CNVs and polymorphisms were conserved within regions but differed across continents, confirming that genomic changes underlying metabolic resistance to insecticides are not universal. By identifying novel DNA markers of insecticide resistance, this study opens the way for tracking down metabolic changes developed by mosquitoes to resist insecticides within and among populations.