CRISPR/Cas gene drives can bias transgene inheritance through different mechanisms. Homing drives are designed to replace a wild-type allele with a copy of a drive element on the homologous chromosome. In Aedes aegypti, the sex-determining locus is closely linked to the white gene, which was previously used as a target for a homing drive element (w^GDe). Here, through an analysis using this linkage we show that in males inheritance bias of w^GDe did not occur by homing, rather through increased propagation of the donor drive element. We test the same w^GDe drive element with transgenes expressing Cas9 with germline regulatory elements sds3, bgcn, and nup50. We only find inheritance bias through homing, even with the identical nup50-Cas9 transgene. We propose that DNA repair outcomes may be more context dependent than anticipated and that other previously reported homing drives may, in fact, bias their inheritance through other mechanisms.

CRISPR/Cas 基因驱动可以通过不同的机制来偏向转基因遗传。归巢驱动器旨在用同源染色体上的驱动元件副本替换野生型等位基因。在埃及伊蚊中，性别决定基因座与白色基因密切相关，该基因先前被用作归巢驱动元件（ w ^GDe ）的靶标。在这里，通过使用这种联系的分析，我们表明，在雄性中， w ^GDe的遗传偏差并不是通过归巢而发生的，而是通过供体驱动元件的传播增加而发生的。我们使用表达带有种系调控元件sds3 、 bgcn和nup50 的Cas9 的转基因测试相同的w ^GDe驱动元件。即使使用相同的nup50 -Cas9 转基因，我们也只能通过归巢发现遗传偏差。我们认为 DNA 修复结果可能比预期更加依赖于环境，并且之前报道的其他归巢驱动实际上可能通过其他机制来偏向其遗传。