Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, 300072, Tianjin, China.
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, 300072, Tianjin, China.
Nat Commun. 2020 Aug 28;11(1):4344. doi: 10.1038/s41467-020-18222-0.
Self-propagating drive systems are capable of causing non-Mendelian inheritance. Here, we report a drive system in yeast referred to as a chromosome drive that eliminates the target chromosome via CRISPR-Cas9, enabling the transmission of the desired chromosome. Our results show that the entire Saccharomyces cerevisiae chromosome can be eliminated efficiently through only one double-strand break around the centromere via CRISPR-Cas9. As a proof-of-concept experiment of this CRISPR-Cas9 chromosome drive system, the synthetic yeast chromosome X is completely eliminated, and the counterpart wild-type chromosome X harboring a green fluorescent protein gene or the components of a synthetic violacein pathway are duplicated by sexual reproduction. We also demonstrate the use of chromosome drive to preferentially transmit complex genetic traits in yeast. Chromosome drive enables entire chromosome elimination and biased inheritance on a chromosomal scale, facilitating genomic engineering and chromosome-scale genetic mapping, and extending applications of self-propagating drives.
自我传播驱动系统能够引起非孟德尔遗传。在这里,我们报告了一种在酵母中称为染色体驱动的驱动系统,该系统通过 CRISPR-Cas9 消除靶染色体,从而实现所需染色体的传递。我们的结果表明,通过 CRISPR-Cas9 在着丝粒周围只有一个双链断裂,就可以有效地消除整个酿酒酵母染色体。作为该 CRISPR-Cas9 染色体驱动系统的概念验证实验,完全消除了合成酵母染色体 X,并且含有绿色荧光蛋白基因或合成紫胶途径组件的对应野生型染色体 X 通过有性生殖进行复制。我们还展示了使用染色体驱动在酵母中优先传递复杂的遗传特征。染色体驱动使整个染色体消除和染色体尺度上的偏向遗传成为可能,促进了基因组工程和染色体尺度的遗传作图,并扩展了自我传播驱动的应用。