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归巢抑制驱动候选物在具有空间结构的模拟中表现出意想不到的性能差异。

homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial structure.

机构信息

Department of Computational Biology, Cornell University, Ithaca, United States.

Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.

出版信息

Elife. 2022 Oct 14;11:e79121. doi: 10.7554/eLife.79121.

Abstract

Recent experiments have produced several homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such drives may be highly effective tools to combat malaria. One such homing drive, based on the promoter driving CRISPR/Cas9, was able to eliminate a cage population of mosquitoes. A second version, purportedly improved upon the first by incorporating an X-shredder element (which biases inheritance towards male offspring), was similarly successful. Here, we analyze experimental data from each of these gene drives to extract their characteristics and performance parameters and compare these to previous interpretations of their experimental performance. We assess each suppression drive within an individual-based simulation framework that models mosquito population dynamics in continuous space. We find that the combined homing/X-shredder drive is actually less effective at population suppression within the context of our mosquito population model. In particular, the combined drive often fails to completely suppress the population, instead resulting in an unstable equilibrium between drive and wild-type alleles. By contrast, otherwise similar drives based on the promoter may prove to be more promising candidates for future development than originally thought.

摘要

最近的实验产生了几种归巢基因驱动,这些驱动会破坏雌性生育基因,从而最终导致种群崩溃。这种驱动可能是对抗疟疾的高效工具。其中一种基于 CRISPR/Cas9 驱动的归巢驱动能够消灭一个笼养蚊子种群。第二个版本据称通过引入 X 切碎器元件(偏向雄性后代的遗传)对第一个版本进行了改进,同样取得了成功。在这里,我们分析了这些基因驱动的实验数据,以提取它们的特征和性能参数,并将其与之前对其实验性能的解释进行比较。我们在个体模拟框架内评估每个抑制驱动,该框架在连续空间中模拟蚊子种群动态。我们发现,在我们的蚊子种群模型中,组合的归巢/X 切碎器驱动实际上在种群抑制方面的效果较差。具体来说,组合驱动往往无法完全抑制种群,而是导致驱动和野生型等位基因之间的不稳定平衡。相比之下,基于 启动子的其他类似驱动可能比最初想象的更有希望成为未来发展的候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c04/9596161/22966f89800b/elife-79121-fig1.jpg

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