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Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae

文献类型： 外文期刊

作者： Cheng L.;Zhao S.;Li T.;Hou S.;Luo Z.;Xu J.;Yu W.;Jiang S.;Monti M.;Schindler D.;Zhang W.;Hou C.;Ma Y.;Cai Y.;Boeke J.D.;Dai J.

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期刊名称： Nature Communications

ISSN： 2041-1723

年卷期： 2024 年 15 卷 1 期

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收录情况： SCIE（2024版）

摘要： 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. © 2024, The Author(s).

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