Building a eukaryotic chromosome arm by de novo design and synthesis

Shuangying Jiang, Zhouqing Luo, Jie Wu, Kang Yu, Shijun Zhao, Zelin Cai, Wenfei Yu, Hui Wang, Li Cheng, Zhenzhen Liang, Hui Gao, Marco Monti, Daniel Schindler, Linsen Huang, Cheng Zeng, Weimin Zhang, Chun Zhou, Yuanwei Tang, Tianyi Li, Yingxin Ma, Yizhi Cai, Jef D. Boeke, Qiao Zhao () and Junbiao Dai ()
Additional contact information
Shuangying Jiang: Chinese Academy of Sciences
Zhouqing Luo: Chinese Academy of Sciences
Jie Wu: Chinese Academy of Sciences
Kang Yu: Chinese Academy of Sciences
Shijun Zhao: Chinese Academy of Sciences
Zelin Cai: Chinese Academy of Sciences
Wenfei Yu: Chinese Academy of Sciences
Hui Wang: Xiamen University
Li Cheng: Chinese Academy of Sciences
Zhenzhen Liang: Chinese Academy of Sciences
Hui Gao: Chinese Academy of Sciences
Marco Monti: University of Manchester
Daniel Schindler: University of Manchester
Linsen Huang: Chinese Academy of Sciences
Cheng Zeng: Chinese Academy of Sciences
Weimin Zhang: NYU Langone Health
Chun Zhou: Chinese Academy of Sciences
Yuanwei Tang: Chinese Academy of Sciences
Tianyi Li: Chinese Academy of Sciences
Yingxin Ma: Chinese Academy of Sciences
Yizhi Cai: Chinese Academy of Sciences
Jef D. Boeke: NYU Langone Health
Qiao Zhao: Chinese Academy of Sciences
Junbiao Dai: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract The genome of an organism is inherited from its ancestor and continues to evolve over time, however, the extent to which the current version could be altered remains unknown. To probe the genome plasticity of Saccharomyces cerevisiae, here we replace the native left arm of chromosome XII (chrXIIL) with a linear artificial chromosome harboring small sets of reconstructed genes. We find that as few as 12 genes are sufficient for cell viability, whereas 25 genes are required to recover the partial fitness defects observed in the 12-gene strain. Next, we demonstrate that these genes can be reconstructed individually using synthetic regulatory sequences and recoded open-reading frames with a “one-amino-acid-one-codon” strategy to remain functional. Finally, a synthetic neochromsome with the reconstructed genes is assembled which could substitute chrXIIL for viability. Together, our work not only highlights the high plasticity of yeast genome, but also illustrates the possibility of making functional eukaryotic chromosomes from entirely artificial sequences.

Date: 2023
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DOI: 10.1038/s41467-023-43531-5

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