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Here, we report the successful design, construction, and characterization of a 770-kilobase synthetic yeast chromosome II (synII). Our study incorporates characterization at multiple levels-including phenomics, transcriptomics, proteomics, chromosome segregation, and replication analysis-to provide a thorough and comprehensive analysis of a synthetic chromosome. Our Trans-Omics analyses reveal a modest but potentially relevant pervasive up-regulation of translational machinery observed in synII, mainly caused by the deletion of 13 transfer RNAs. By both complementation assays and SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution), we targeted and debugged the origin of a growth defect at 37°C in glycerol medium, which is related to misregulation of the high-osmolarity glycerol response. Despite the subtle differences, the synII strain shows highly consistent biological processes comparable to the native strain. Copyright © 2017, American Association for the Advancement of Science.

Citation

Yue Shen, Yun Wang, Tai Chen, Feng Gao, Jianhui Gong, Dariusz Abramczyk, Roy Walker, Hongcui Zhao, Shihong Chen, Wei Liu, Yisha Luo, Carolin A Müller, Adrien Paul-Dubois-Taine, Bonnie Alver, Giovanni Stracquadanio, Leslie A Mitchell, Zhouqing Luo, Yanqun Fan, Baojin Zhou, Bo Wen, Fengji Tan, Yujia Wang, Jin Zi, Zexiong Xie, Bingzhi Li, Kun Yang, Sarah M Richardson, Hui Jiang, Christopher E French, Conrad A Nieduszynski, Romain Koszul, Adele L Marston, Yingjin Yuan, Jian Wang, Joel S Bader, Junbiao Dai, Jef D Boeke, Xun Xu, Yizhi Cai, Huanming Yang. Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome. Science (New York, N.Y.). 2017 Mar 10;355(6329)

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PMID: 28280153

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