Bug mapping and fitness testing of chemically synthesized chromosome X

Yi Wu, Bing-Zhi Li, Meng Zhao, Leslie A. Mitchell, Ze-Xiong Xie, Qiu-Hui Lin, Xia Wang, Wen-Hai Xiao, Ying Wang, Xiao Zhou, Hong Liu, Xia Li, Ming-Zhu Ding, Duo Liu, Lu Zhang, Bao-Li Liu, Xiao-Le Wu, Fei-Fei Li, Xiu-Tao Dong, Bin Jia & 26 others Wen-Zheng Zhang, Guo-Zhen Jiang, Yue Liu, Xue Bai, Tian-Qing Song, Yan Chen, Si-Jie Zhou, Rui-Ying Zhu, Feng Gao, Zheng Kuang, Xuya Wang, Michael Shen, Kun Yang, Giovanni Stracquadanio, Sarah M. Richardson, Yicong Lin, Lihui Wang, Roy Walker, Yisha Luo, Ping-Sheng Ma, Huanming Yang, Yizhi Cai, Junbiao Dai, Joel S. Bader, Jef D. Boeke, Ying-Jin Yuan

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Debugging a genome sequence is imperative for successfully building a synthetic genome. As part of the effort to build a designer eukaryotic genome, yeast synthetic chromosome X (synX), designed as 707,459 base pairs, was synthesized chemically. SynX exhibited good fitness under a wide variety of conditions. A highly efficient mapping strategy called pooled PCRTag mapping (PoPM), which can be generalized to any watermarked synthetic chromosome, was developed to identify genetic alterations that affect cell fitness ("bugs"). A series of bugs were corrected that included a large region bearing complex amplifications, a growth defect mapping to a recoded sequence in FIP1, and a loxPsym site affecting promoter function of ATP2. PoPM is a powerful tool for synthetic yeast genome debugging and an efficient strategy for phenotype-genotype mapping.

Original languageEnglish
Article numbereaaf4706
Pages (from-to)1-6
Number of pages8
JournalScience
Volume355
Issue number6329
DOIs
Publication statusPublished - 10 Mar 2017
Externally publishedYes

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  • Cite this

    Wu, Y., Li, B-Z., Zhao, M., Mitchell, L. A., Xie, Z-X., Lin, Q-H., ... Yuan, Y-J. (2017). Bug mapping and fitness testing of chemically synthesized chromosome X. Science, 355(6329), 1-6. [eaaf4706]. https://doi.org/10.1126/science.aaf4706