Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome

Yue Shen (1, 2, 3, 4) , Yun Wang (2, 4) , Tai Chen (2, 4) , Feng Gao (2) , Jianhui Gong (2) , Dariusz Abramczyk (1) , Roy Walker (1) , Hongcui Zhao (2) , Shihong Chen (2) , Wei Liu (1) , Yisha Luo (1) , Carolin A Müller (5) , Adrien Paul-Dubois-Taine (1) , Bonnie Alver (1) , Giovanni Stracquadanio (6, 7) , Leslie Mitchell (8) , Zhouqing Luo (9) , Yanqun Fan (2) , Baojin Zhou (2) , Bo Wen (2) , Fengji Tan (2) , Yujia Wang (2) , Jin Zi (2) , Zexiong Xie (10) , Bingzhi Li (10) , Kun Yang (6) , Sarah Richardson (6, 7) , Hui Jiang (2) , Christopher French (1) , Conrad A Nieduszynski (5) , Romain Koszul (11) , Adele Marston (1) , Yingjin Yuan (10) , Jian Wang (2) , Joel Bader (7, 8) , Junbiao Dai (9) , Jef Boeke (8) , Xun Xu (2, 4) , Yizhi Cai (1) , Huanming Yang (2, 3)

1 University of Edinburgh
2 BGI - Beijing Genomics Institute [Shenzhen]
3 James D. Watson Institute of Genome Sciences
4 BGI Qingdao
5 Sir William Dunn School of Pathology [Oxford]
6 High Throughput Biology Center [Baltimore]
7 JHU - Johns Hopkins University
8 NYU Langone Medical Center - New York University Langone Medical Center
9 THU - Tsinghua University [Beijing]
10 TJU - Tianjin University
11 Régulation spatiale des Génomes - Spatial Regulation of Genomes

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.

Domains: Life Sciences [q-bio]

Yue Shen, Yun Wang, Tai Chen, Feng Gao, Jianhui Gong, et al.. Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome. Science, 2017, 355 (6329), pp.eaaf4791. ⟨10.1126/science.aaf4791⟩. ⟨pasteur-02868099⟩