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 MaYizhi Cai, Jef D. Boeke, Qiao Zhao, Junbiao Dai

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number7886
JournalNature communications
Issue number1
StatePublished - Dec 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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