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Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae

Author

Listed:
  • Li Cheng

    (Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Shijun Zhao

    (Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Tianyi Li

    (Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
    Shenzhen Lianghe Biotechnology Co., Ltd.)

  • Sha Hou

    (Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Zhouqing Luo

    (Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
    Xiamen University)

  • Jinsheng Xu

    (Huazhong Agricultural University)

  • Wenfei Yu

    (Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shuangying Jiang

    (Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Marco Monti

    (University of Manchester)

  • Daniel Schindler

    (University of Manchester)

  • Weimin Zhang

    (Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Langone Health)

  • Chunhui Hou

    (China State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences)

  • Yingxin Ma

    (Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Yizhi Cai

    (Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
    University of Manchester)

  • Jef D. Boeke

    (Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Langone Health
    NYU Tandon School of Engineering)

  • Junbiao Dai

    (Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences
    Shenzhen University)

Abstract

Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) is a promising tool to study genomic rearrangements. However, the potential of SCRaMbLE to study genomic rearrangements is currently hindered, because a strain containing all 16 synthetic chromosomes is not yet available. Here, we construct SparLox83R, a yeast strain containing 83 loxPsym sites distributed across all 16 chromosomes. SCRaMbLE of SparLox83R produces versatile genome-wide genomic rearrangements, including inter-chromosomal events. Moreover, when combined with synthetic chromosomes, SCRaMbLE of hetero-diploids with SparLox83R leads to increased diversity of genomic rearrangements and relatively faster evolution of traits compared to hetero-diploids only with wild-type chromosomes. Analysis of the SCRaMbLEd strain with increased tolerance to nocodazole demonstrates that genomic rearrangements can perturb the transcriptome and 3D genome structure and consequently impact phenotypes. In summary, a genome with sparsely distributed loxPsym sites can serve as a powerful tool for studying the consequence of genomic rearrangements and accelerating strain engineering in Saccharomyces cerevisiae.

Suggested Citation

  • Li Cheng & Shijun Zhao & Tianyi Li & Sha Hou & Zhouqing Luo & Jinsheng Xu & Wenfei Yu & Shuangying Jiang & Marco Monti & Daniel Schindler & Weimin Zhang & Chunhui Hou & Yingxin Ma & Yizhi Cai & Jef D., 2024. "Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44511-5
    DOI: 10.1038/s41467-023-44511-5
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