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全基因组测序揭示布基纳法索纵向研究中主要疟疾媒介对新杀虫剂抗性变体的进化。

Whole-genome sequencing of major malaria vectors reveals the evolution of new insecticide resistance variants in a longitudinal study in Burkina Faso.

机构信息

Institut de Recherche en Sciences de la Santé (IRSS), 01 BP 545, Bobo-Dioulasso 01, Burkina Faso.

Université Nazi Boni, 01 BP 1091, Bobo-Dioulasso, Burkina Faso.

出版信息

Malar J. 2024 Sep 17;23(1):280. doi: 10.1186/s12936-024-05106-7.

DOI:10.1186/s12936-024-05106-7
PMID:39285410
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11406867/
Abstract

BACKGROUND

Intensive deployment of insecticide based malaria vector control tools resulted in the rapid evolution of phenotypes resistant to these chemicals. Understanding this process at the genomic level is important for the deployment of successful vector control interventions. Therefore, longitudinal sampling followed by whole genome sequencing (WGS) is necessary to understand how these evolutionary processes evolve over time. This study investigated the change in genetic structure and the evolution of the insecticide resistance variants in natural populations of Anopheles gambiae over time and space from 2012 to 2017 in Burkina Faso.

METHODS

New genomic data have been generated from An. gambiae mosquitoes collected from three villages in the western part of Burkina Faso between 2012 and 2017. The samples were whole-genome sequenced and the data used in the An. gambiae 1000 genomes (Ag1000G) project as part of the Vector Observatory. Genomic data were analysed using the analysis pipeline previously designed by the Ag1000G project.

RESULTS

The results showed similar and consistent nucleotide diversity and negative Tajima's D between An. gambiae sensu stricto (s.s.) and Anopheles coluzzii. Principal component analysis (PCA) and the fixation index (F) showed a clear genetic structure in the An. gambiae sensu lato (s.l.) species. Genome-wide F and H12 scans identified genomic regions under divergent selection that may have implications in the adaptation to ecological changes. Novel voltage-gated sodium channel pyrethroid resistance target-site alleles (V402L, I1527T) were identified at increasing frequencies alongside the established alleles (Vgsc-L995F, Vgsc-L995S and N1570Y) within the An. gambiae s.l.

POPULATIONS

Organophosphate metabolic resistance markers were also identified, at increasing frequencies, within the An. gambiae s.s. populations from 2012 to 2017, including the SNP Ace1-G280S and its associated duplication. Variants simultaneously identified in the same vector populations raise concerns about the long-term efficacy of new generation bed nets and the recently organophosphate pirimiphos-methyl indoor residual spraying in Burkina Faso.

CONCLUSION

These findings highlighted the benefit of genomic surveillance of malaria vectors for the detection of new insecticide resistance variants, the monitoring of the existing resistance variants, and also to get insights into the evolutionary processes driving insecticide resistance.

摘要

背景

基于杀虫剂的疟疾媒介控制工具的密集部署导致了对这些化学物质具有抗性的表型迅速进化。从基因组水平上了解这一过程对于成功实施媒介控制干预措施非常重要。因此,需要进行纵向采样和全基因组测序(WGS),以了解这些进化过程随时间的变化。本研究调查了 2012 年至 2017 年间布基纳法索西部三个村庄自然种群中按蚊的遗传结构变化和杀虫剂抗性变体的进化情况。

方法

从 2012 年至 2017 年期间布基纳法索西部的三个村庄采集的按蚊中获得了新的基因组数据。对这些样本进行了全基因组测序,并将数据用作 Vector Observatory 中 Ag1000G 项目的一部分。使用 Ag1000G 项目之前设计的分析管道对基因组数据进行了分析。

结果

结果表明,在按蚊 sensu stricto(s.s.)和按蚊 coluzzii 之间,核苷酸多样性和负 Tajima 的 D 相似且一致。主成分分析(PCA)和固定指数(F)显示,在按蚊 sensu lato(s.l.)物种中存在明显的遗传结构。全基因组 F 和 H12 扫描确定了可能对适应生态变化有影响的分歧选择的基因组区域。新型电压门控钠离子通道拟除虫菊酯抗性靶位等位基因(V402L,I1527T)与已建立的等位基因(Vgsc-L995F,Vgsc-L995S 和 N1570Y)一起在按蚊 s.l. 种群中以增加的频率出现。

种群

2012 年至 2017 年间,在按蚊 s.s. 种群中还发现了有机磷代谢抗性标记物,其频率也在增加,包括 SNP Ace1-G280S 及其相关的重复。在同一媒介种群中同时鉴定出的变异体引起了人们对新一代蚊帐和布基纳法索新的有机磷杀虫剂吡虫啉室内滞留喷洒长期效果的关注。

结论

这些发现强调了对疟疾媒介进行基因组监测以检测新的杀虫剂抗性变体、监测现有的抗性变体以及深入了解驱动杀虫剂抗性的进化过程的好处。

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