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Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae

文献类型: 外文期刊

作者: Cheng, Li 1 ; Zhao, Shijun 1 ; Li, Tianyi 1 ; Hou, Sha 1 ; Luo, Zhouqing 1 ; Xu, Jinsheng 4 ; Yu, Wenfei 1 ; Jiang, Shuangying 1 ; Monti, Marco 5 ; Schindler, Daniel 5 ; Zhang, Weimin 6 ; Hou, Chunhui 8 ; Ma, Yingxin 1 ; Cai, Yizhi 1 ; Boeke, Jef D. 6 ; Dai, Junbiao 1 ;

作者机构: 1.Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, Key Lab Quantitat Synthet Biol,Shenzhen Key Lab Sy, Shenzhen 518055, Peoples R China

2.Univ Chinese Acad Sci, Beijing, Peoples R China

3.Xiamen Univ, Innovat Ctr Cell Signaling Network, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Fujian, Peoples R China

4.Huazhong Agr Univ, Dept Bioinformat, Wuhan 430070, Hubei, Peoples R China

5.Univ Manchester, Manchester Inst Biotechnol, Manchester M1 7DN, England

6.NYU Langone Hlth, Inst Syst Genet, New York, NY USA

7.NYU Langone Hlth, Dept Biochem & Mol Pharmacol, New York, NY USA

8.Chinese Acad Sci, Kunming Inst Zool, China State Key Lab Genet Resources & Evolut, Kunming 650223, Peoples R China

9.NYU Tandon Sch Engn, Dept Biomed Engn, Brooklyn, NY 11201 USA

10.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Shenzhen Branch, Minist Agr & Rural Affairs,Guangdong Lab Lingnan M, Shenzhen, Peoples R China

11.Shenzhen Univ, Coll Life Sci & Oceanog, 1066 Xueyuan Rd, Shenzhen 518055, Guangdong, Peoples R China

12.Shenzhen Lianghe Biotechnol Co Ltd, Shenzhen, Peoples R China

期刊名称:NATURE COMMUNICATIONS ( 影响因子:16.6; 五年影响因子:17.0 )

ISSN:

年卷期: 2024 年 15 卷 1 期

页码:

收录情况: SCI

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.

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