丰富的保守 CRISPR-Cas9 靶位存在于高度多态的疟蚊和伊蚊基因组中。
Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes mosquitoes.
机构信息
Vector Genetics Laboratory, Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
Winclove Probiotics, Hulstweg 11, 1032 LB, Amesterdam, Netherlands.
出版信息
Nat Commun. 2020 Mar 18;11(1):1425. doi: 10.1038/s41467-020-15204-0.
A number of recent papers report that standing genetic variation in natural populations includes ubiquitous polymorphisms within target sites for Cas9-based gene drive (CGD) and that these "drive resistant alleles" (DRA) preclude the successful application of CGD for managing these populations. Here we report the results of a survey of 1280 genomes of the mosquitoes Anopheles gambiae, An. coluzzii, and Aedes aegypti in which we determine that ~90% of all protein-encoding CGD target genes in natural populations include at least one target site with no DRAs at a frequency of ≥1.0%. We conclude that the abundance of conserved target sites in mosquito genomes and the inherent flexibility in CGD design obviates the concern that DRAs present in the standing genetic variation of mosquito populations will be detrimental to the deployment of this technology for population modification strategies.
许多近期的论文报告指出，自然种群中的遗传变异包括 Cas9 基因为基础的基因驱动（CGD）靶点内普遍存在的多态性，而这些“驱动抗性等位基因”（DRA）会排除 CGD 成功应用于管理这些种群的可能性。在这里，我们报告了对 1280 个疟蚊属（Anopheles）、按蚊属（An. coluzzii）和埃及伊蚊（Aedes aegypti）基因组的调查结果，我们确定在自然种群中，约 90%的所有 CGD 靶点的编码蛋白基因至少有一个靶点，在频率≥1.0%的情况下没有 DRA。我们的结论是，蚊子基因组中保守靶点的丰富性和 CGD 设计的固有灵活性消除了一个担忧，即蚊子种群中存在的遗传变异中的 DRA 会对该技术用于种群改良策略的部署产生不利影响。
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