Dissecting aneuploidy phenotypes by constructing Sc2.0 chromosome VII and 
SCRaMbLEing synthetic disomic yeast

Shen, Yue; Gao, Feng; Wang, Yun; Wang, Yuerong; Zheng, Ju; Gong, Jianhui; Zhang, Jintao; Luo, Zhouqing; Schindler, Daniel; Deng, Yang; Ding, Weichao; Lin, Tao; Swidah, Reem; Zhao, Hongcui; Jiang, Shuangying; Zeng, Cheng; Chen, Shihong; Chen, Tai; Wang, Yong; Luo, Yisha; Mitchell, Leslie; Bader, Joel S.; Zhang, Guojie; Shen, Xia; Wang, Jian; Fu, Xian; Dai, Junbiao; Boeke, Jef D.; Yang, Huanming; Xu, Xun; Cai, Yizhi

doi:10.1016/j.xgen.2023.100364

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Dissecting aneuploidy phenotypes by constructing Sc2.0 chromosome VII and SCRaMbLEing synthetic disomic yeast

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Schindler, Daniel
Core Facility MPG MAXGenesys DNAfoundry, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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https://doi.org/10.1016/j.xgen.2023.100364
(Publisher version)

https://doi.org/10.1101/2022.09.01.506252
(Preprint)

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Citation

Shen, Y., Gao, F., Wang, Y., Wang, Y., Zheng, J., Gong, J., et al. (2023). Dissecting aneuploidy phenotypes by constructing Sc2.0 chromosome VII and SCRaMbLEing synthetic disomic yeast. Cell genomics, 3(11): 100364. doi:10.1016/j.xgen.2023.100364.

Cite as: https://hdl.handle.net/21.11116/0000-000D-E724-6

Abstract

Summary
Aneuploidy compromises genomic stability, often leading to embryo inviability, and is frequently associated with tumorigenesis and aging. Different aneuploid chromosome stoichiometries lead to distinct transcriptomic and phenotypic changes, making it helpful to study aneuploidy in tightly controlled genetic backgrounds. By deploying the engineered SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution) system to the newly synthesized megabase Sc2.0 chromosome VII (synVII), we constructed a synthetic disomic yeast and screened hundreds of SCRaMbLEd derivatives with diverse chromosomal rearrangements. Phenotypic characterization and multi-omics analysis revealed that fitness defects associated with aneuploidy could be restored by (1) removing most of the chromosome content or (2) modifying specific regions in the duplicated chromosome. These findings indicate that both chromosome copy number and specific chromosomal regions contribute to the aneuploidy-related phenotypes, and the synthetic chromosome resource opens new paradigms in studying aneuploidy.