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首页> 外文期刊>PLoS Genetics >A fly model establishes distinct mechanisms for synthetic CRISPR/Cas9 sex distorters
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A fly model establishes distinct mechanisms for synthetic CRISPR/Cas9 sex distorters

机译：一架飞行模型为合成CRISPR / CAS9性扭曲建立了独特的机制

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Synthetic sex distorters have recently been developed in the malaria mosquito, relying on endonucleases that target the X-chromosome during spermatogenesis. Although inspired by naturally-occurring traits, it has remained unclear how they function and, given their potential for genetic control, how portable this strategy is across species. We established Drosophila models for two distinct mechanisms for CRISPR/Cas9 sex-ratio distortion—“X-shredding” and “X-poisoning”—and dissected their target-site requirements and repair dynamics. X-shredding resulted in sex distortion when Cas9 endonuclease activity occurred during the meiotic stages of spermatogenesis but not when Cas9 was expressed from the stem cell stages onwards. Our results suggest that X-shredding is counteracted by the NHEJ DNA repair pathway and can operate on a single repeat cluster of non-essential sequences, although the targeting of a number of such repeats had no effect on the sex ratio. X-poisoning by contrast, i.e. targeting putative haplolethal genes on the X chromosome, induced a high bias towards males (&92%) when we directed Cas9 cleavage to the X-linked ribosomal target gene RpS6 . In the case of X-poisoning sex distortion was coupled to a loss in reproductive output, although a dominant-negative effect appeared to drive the mechanism of female lethality. These model systems will guide the study and the application of sex distorters to medically or agriculturally important insect target species.
机译：最近在疟疾蚊子中开发了合成性扭曲，依赖于在精子发生期间靶向X-染色体的内切核酸酶。尽管受到自然发生的特征的启发，但它仍然尚不清楚它们如何运作，并且鉴于遗传控制的潜力，这种策略在物种中有多便携。我们建立了两种不同机制的果蝇模型，用于克里普尔/ Cas9性别比失真 - “X-inredding”和“X-中毒” - 解剖其目标现场要求和修复动态。 X-粉碎导致性畸变当Cas9内切核酸酶活性在精子发生的白聚乙酸阶段发生时，但是当Cas9从干细胞阶段发出时没有。我们的研究结果表明，NHEJ DNA修复途径抵消了X型粉碎，并且可以在单一重复的非必要序列集群上运行，尽管靶向许多这种重复的靶向对性别比没有影响。相反，X-中毒，即靶向X染色体上的推定的再溶解基因，当我们将Cas9切割到X连接的核糖体靶基因RPS6时，诱导致麦芽（＆ 92％）的高偏差。在X-中毒的情况下，性失真耦合到生殖输出的损失，尽管似乎驱动了雌性致死率的机制。这些模型系统将指导研究和性扭曲对医学或农业上重要的昆虫靶物种的应用。

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