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Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae

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Zitation

Cheng, L., Zhao, S., Li, T., Hou, S., Luo, Z., Xu, J., et al. (2024). Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae. Nature Communications, 15(1): 770. doi:10.1038/s41467-023-44511-5.


Zitierlink: https://hdl.handle.net/21.11116/0000-000E-7FA0-F
Zusammenfassung
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.