Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae

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. Boeke, Junbiao Dai

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number770
JournalNature communications
Issue number1
StatePublished - Dec 2024

ASJC Scopus subject areas

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


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