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疟蚊,按蚊属,在遗传和地理种群结构上为开创性的、限定基因驱动释放提供了一个候选系统。

Genetic and geographic population structure in the malaria vector, Anopheles farauti, provides a candidate system for pioneering confinable gene-drive releases.

机构信息

School of the Environment, University of Queensland, St Lucia, Brisbane, QLD, Australia.

Solomon Islands Ministry of Health, Honiara, Guadalcanal, Solomon Islands.

出版信息

Heredity (Edinb). 2024 May;132(5):232-246. doi: 10.1038/s41437-024-00677-2. Epub 2024 Mar 18.

Abstract

Indoor insecticide applications are the primary tool for reducing malaria transmission in the Solomon Archipelago, a region where Anopheles farauti is the only common malaria vector. Due to the evolution of behavioural resistance in some An. farauti populations, these applications have become less effective. New malaria control interventions are therefore needed in this region, and gene-drives provide a promising new technology. In considering developing a population-specific (local) gene-drive in An. farauti, we detail the species' population genetic structure using microsatellites and whole mitogenomes, finding many spatially confined populations both within and between landmasses. This strong population structure suggests that An. farauti would be a useful system for developing a population-specific, confinable gene-drive for field release, where private alleles can be used as Cas9 targets. Previous work on Anopheles gambiae has used the Cardinal gene for the development of a global population replacement gene-drive. We therefore also analyse the Cardinal gene to assess whether it may be a suitable target to engineer a gene-drive for the modification of local An. farauti populations. Despite the extensive population structure observed in An. farauti for microsatellites, only one remote island population from Vanuatu contained fixed and private alleles at the Cardinal locus. Nonetheless, this study provides an initial framework for further population genomic investigations to discover high-frequency private allele targets in localized An. farauti populations. This would enable the development of gene-drive strains for modifying localised populations with minimal chance of escape and may provide a low-risk route to field trial evaluations.

摘要

室内杀虫剂的应用是减少所罗门群岛疟疾传播的主要手段,该地区只有斑蚊是常见的疟疾传播媒介。由于一些斑蚊种群的行为抗性进化,这些应用的效果已经降低。因此,该地区需要新的疟疾控制干预措施,而基因驱动提供了一种有前途的新技术。在考虑在斑蚊中开发特定种群(本地)的基因驱动时,我们使用微卫星和整个线粒体基因组详细描述了该物种的种群遗传结构,发现许多在陆地内部和之间的空间受限种群。这种强烈的种群结构表明,斑蚊将是开发用于野外释放的特定种群、可限制的基因驱动的有用系统,其中私有等位基因可以用作 Cas9 靶点。以前关于冈比亚按蚊的工作已经使用 Cardinal 基因开发了一种全球种群替换基因驱动。因此,我们还分析了 Cardinal 基因,以评估它是否可以作为工程化基因驱动的合适靶点,用于修饰当地的斑蚊种群。尽管在斑蚊中观察到微卫星的广泛种群结构,但只有来自瓦努阿图的一个偏远岛屿种群在 Cardinal 基因座上存在固定和私有等位基因。尽管如此,这项研究为进一步的种群基因组学研究提供了一个初步框架,以发现本地化的斑蚊种群中高频的私有等位基因靶点。这将使我们能够开发基因驱动菌株来修饰本地化的种群,最大限度地减少逃逸的机会,并且可能为田间试验评估提供低风险的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e29/11074138/b4a7353eeea0/41437_2024_677_Fig1_HTML.jpg

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