title: Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome.
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 byloxP-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.
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.|School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.|James D. Watson Institute of Genome Sciences, Hangzhou 310058, China.|BGI-Qingdao, Qingdao 266555, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.|BGI-Qingdao, Qingdao 266555, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.|BGI-Qingdao, Qingdao 266555, China.
authors.forename: Tai
authors.initials: T
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Gong
authors.affiliation: School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Abramczyk
authors.affiliation: School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.
authors.forename: Roy
authors.initials: R
authors.lastname: Walker
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Hongcui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Shihong
authors.initials: S
authors.lastname: Chen
authors.affiliation: School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.
authors.forename: Yisha
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
authors.forename: Carolin A
authors.initials: CA
authors.lastname: Müller
authors.affiliation: School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.
authors.forename: Adrien
authors.initials: A
authors.lastname: Paul-Dubois-Taine
authors.affiliation: School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Alver
authors.affiliation: High-Throughput Biology Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 21205 USA.|Department of Biomedical Engineering, School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218 USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stracquadanio
authors.affiliation: Institute for Systems Genetics, NYU Langone Medical Center, ACLSW Room 503, 430 East 29th Street, New York, NY 10016.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Mitchell
authors.affiliation: Key Laboratory of Industrial Biocatalysis (Ministry of Education), Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhouqing
authors.initials: Z
authors.lastname: Luo
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Fan
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Baojin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wen
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Fengji
authors.initials: F
authors.lastname: Tan
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zi
authors.affiliation: 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.
authors.forename: Zexiong
authors.initials: Z
authors.lastname: Xie
authors.affiliation: 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.
authors.forename: Bingzhi
authors.initials: B
authors.lastname: Li
authors.affiliation: High-Throughput Biology Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 21205 USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: High-Throughput Biology Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 21205 USA.|Department of Biomedical Engineering, School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218 USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Richardson
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: French
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
authors.forename: Conrad A
authors.initials: CA
authors.lastname: Nieduszynski
authors.affiliation: Department of Genomes and Genetics, Institut Pasteur / CNRS UMR3525, 25-28, rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Koszul
authors.affiliation: School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.
authors.forename: Adele L
authors.initials: AL
authors.lastname: Marston
authors.affiliation: 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.
authors.forename: Yingjin
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218 USA.|Institute for Systems Genetics, NYU Langone Medical Center, ACLSW Room 503, 430 East 29th Street, New York, NY 10016.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Bader
authors.affiliation: Key Laboratory of Industrial Biocatalysis (Ministry of Education), Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Junbiao
authors.initials: J
authors.lastname: Dai
authors.affiliation: Institute for Systems Genetics, NYU Langone Medical Center, ACLSW Room 503, 430 East 29th Street, New York, NY 10016.
authors.forename: Jef D
authors.initials: JD
authors.lastname: Boeke
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.|BGI-Qingdao, Qingdao 266555, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Cai
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.|James D. Watson Institute of Genome Sciences, Hangzhou 310058, China.
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
mesh_terms: D020090:Chromosome Segregation; D018244:Chromosomes, Artificial, Yeast / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003470:Culture Media / Q000737:chemistry; D004261:DNA Replication; D016681:Genome, Fungal; D005990:Glycerol; D040901:Proteomics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D017422:Sequence Analysis, DNA; D058615:Synthetic Biology; D059467:Transcriptome
chemical_list: D003470:Culture Media; D005990:Glycerol