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Science. 2017 Mar 10;355(6329). pii: eaaf4791. doi: 10.1126/science.aaf4791.

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

Author information

1
BGI-Shenzhen, Shenzhen 518083, China.
2
School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.
3
James D. Watson Institute of Genome Sciences, Hangzhou 310058, China.
4
BGI-Qingdao, Qingdao 266555, China.
5
Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
6
High-Throughput Biology Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 21205 USA.
7
Department of Biomedical Engineering, School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218 USA.
8
Institute for Systems Genetics, NYU Langone Medical Center, ACLSW Room 503, 430 East 29th Street, New York, NY 10016.
9
Key Laboratory of Industrial Biocatalysis (Ministry of Education), Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
10
Key Laboratory of Systems Bioengineering (Ministry of Education), SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, PR China.
11
Department of Genomes and Genetics, Institut Pasteur / CNRS UMR3525, 25-28, rue du Docteur Roux, 75724 Paris Cedex 15, France.
#
Contributed equally

Abstract

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.

PMID:
28280153
PMCID:
PMC5390853
DOI:
10.1126/science.aaf4791
[Indexed for MEDLINE]
Free PMC Article

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