Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus.
Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus.
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DOI：
10.1371/journal.pgen.1009253
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发表时间：
2021-01
期刊：
影响因子：
4.5
通讯作者：
Anopheles gambiae 1000 Genomes Consortium
中科院分区：
文献类型：
--
作者：
Grau-Bové X;Lucas E;Pipini D;Rippon E;van 't Hof AE;Constant E;Dadzie S;Egyir-Yawson A;Essandoh J;Chabi J;Djogbénou L;Harding NJ;Miles A;Kwiatkowski D;Donnelly MJ;Weetman D;Anopheles gambiae 1000 Genomes Consortium
使用杀虫剂控制病媒种群是目前在非洲预防疟疾传播战略的一个关键要素。引入有效的杀虫剂，如有机磷酸酯-甲基哌啶磷，对于克服由高度多样化的按蚊基因组驱动的反复出现的耐药性至关重要。本研究采用种群基因组学方法研究了主要疟疾媒介冈比亚按蚊和科鲁兹按蚊对吡米磷抗性的基础。拷贝数变异和乙酰胆碱酯酶基因Ace1的单一非同义替换的组合，为来自Côte d 'Ivoire的A. coluzzii种群提供了关键的抗性诊断，我们将其用于基于序列的关联图谱，并在其他西非种群中进行了复制。Ace1的替换和复制发生在冈比亚拟虫中一种独特的抗性单倍型上，这种抗性单倍型在冈比亚拟虫中进化并渗入到coluzzii中，现在在西非很常见，主要是由于其他有机磷或氨基甲酸酯类杀虫剂施加的选择。我们的研究结果强调了这种复杂抗性单倍型对表型抗性的预测价值，并阐明了其进化史，为分子监测当前和未来基于甲基哌啶磷的干预措施的有效性提供了工具。通过杀虫工具或干预措施控制蚊子种群是减少疟疾传播运动的主要内容。然而，特别是在撒哈拉以南非洲，对疟按蚊最重要的种类持续的杀虫选择压力，有利于进化选择日益有效的抗性机制。我们调查了对有机磷酸酯甲胺磷抗性的遗传基础，甲胺磷是目前在非洲室内残留喷洒运动中使用的主要杀虫剂。对科特迪瓦一个种群进行的全基因组关联分析表明，耐药标本在乙酰胆碱酯酶这一基因中具有独特的突变组合，这是吡吡磷-甲基耐药的主要原因。在涉及两种主要疟疾病媒——科鲁兹疟蚊和冈比亚疟蚊——的诊断分析中对这些突变进行的进一步检测，证实了它们可作为吡虫磷-甲基耐药性的信息性预测因子。利用来自更广泛地区（布基纳法索、Côte科特迪瓦、加纳和几内亚）的大量全基因组测序标本的数据，我们的进化分析表明，这些突变出现在a . gambiae中，并通过种间杂交转移到a . coluzzii中。我们的研究结果显示了主要疟疾媒介的耐药机制是如何发展和传播的，并为分子监测提供了有效的工具，为公共卫生运动提供信息。
Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Côte d’Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa primarily due to selection imposed by other organophosphate or carbamate insecticides. Our findings highlight the predictive value of this complex resistance haplotype for phenotypic resistance and clarify its evolutionary history, providing tools to for molecular surveillance of the current and future effectiveness of pirimiphos-methyl based interventions. Control of mosquito populations via insecticidal tools or interventions is a mainstay of campaigns to reduce malaria transmission. However, especially in sub-Saharan Africa, continued insecticidal selection pressure on the most important species of Anopheles malaria mosquitoes has favoured the evolutionary selection of increasingly effective resistance mechanisms. We investigate the genetic basis of resistance to the organophosphate pirimiphos-methyl, the dominant insecticide now used for indoor residual spraying campaigns in Africa. Genome-wide association analysis of a population from Cote d’Ivoire showed that resistant specimens share a unique combination of mutations in one gene, the acetylcholinesterase enzyme, which constitute the prime cause of pirimiphos-methyl resistance. Further testing of these mutations in diagnostic assays involving two major malaria vectors, A. coluzzii and A. gambiae, validate their use as informative predictors of pirimiphos-methyl resistance. Using data from a large collection of whole genome sequenced specimens from a broader range of locations (Burkina-Faso, Côte d’Ivoire, Ghana, and Guinea), our evolutionary analyses demonstrate that these mutations emerged in A. gambiae and transferred into A. coluzzii by inter-specific hybridisation. Our results show how resistance mechanisms in key malaria vectors have developed and spread, and provide validated tools for molecular surveillance to inform public health campaigns.
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影响因子：
10.7
作者：
Minh BQ;Nguyen MA;von Haeseler A
通讯作者：
von Haeseler A
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
3.2
作者：
Dengela, Dereje;Seyoum, Aklilu;Fornadel, Christen M.
通讯作者：
Fornadel, Christen M.
影响因子：
10.7
作者：
Hoang DT;Chernomor O;von Haeseler A;Minh BQ;Vinh LS
通讯作者：
Vinh LS
DOI：
10.1093/bioinformatics/btp348
发表时间：
2009-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Capella-Gutiérrez S;Silla-Martínez JM;Gabaldón T
通讯作者：
Gabaldón T