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

• DOI: 10.1016/j.xgen.2023.100364
• Publication Date: 2023-11-09T16:50:22Z
• Authors: Yue Shen; Feng Gao; Yun Wang; Yuerong Wang; Ju Zheng; Jianhui Gong; Jintao Zhang; Zhouqing Luo; Daniel Schindler; Yang Deng; Weichao Ding; Tao Lin; Reem Swidah; Hongcui Zhao; Shuangying Jiang; Cheng Zeng; Shihong Chen; Tai Chen; Yong Wang; Yisha Luo; Leslie Mitchell; Joel S. Bader; Guojie Zhang; Xia Shen; Jian Wang; Xian Fu; Junbiao Dai; Jef D. Boeke; Huanming Yang; Xun Xu; Yizhi Cai
• Keywords: 0301 basic medicine; Genome Evolution and Polyploidy in Plants; synVII; aneuploidy phenotypes; synthetic genomics; SCRaMbLE; Plant Science; Chromosome; Gene; Article; Agricultural and Biological Sciences; 03 medical and health sciences; Ploidy; Biochemistry, Genetics and Molecular Biology; Chromosomal Instability; Chromosome Duplication; Genetics; Molecular Biology; Biology; Genome; Genomic Expression and Function in Yeast Organism; Life Sciences; synthetic disomic yeast; Cell Biology; Regulation and Function of Microtubules in Cell Division; Aneuploidy; Chromosome segregation; Phenotype; FOS: Biological sciences; aneuploidy recovery approaches; growth rate

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