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; 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

doi:10.1126/science.aaf4706

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 JiaWen-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 journal › Article › peer-review

146 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 language	English
Article number	eaaf4706
Pages (from-to)	1-6
Number of pages	8
Journal	Science
Volume	355
Issue number	6329
DOIs	https://doi.org/10.1126/science.aaf4706
Publication status	Published - 10 Mar 2017
Externally published	Yes

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10.1126/science.aaf4706

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Wu, Y., Li, B-Z., Zhao, M., Mitchell, L. A., Xie, Z-X., Lin, Q-H., Wang, X., Xiao, W-H., Wang, Y., Zhou, X., Liu, H., Li, X., Ding, M-Z., Liu, D., Zhang, L., Liu, B-L., Wu, X-L., Li, F-F., Dong, X-T., ... 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

Wu, Yi ; Li, Bing-Zhi ; Zhao, Meng ; Mitchell, Leslie A. ; Xie, Ze-Xiong ; Lin, Qiu-Hui ; Wang, Xia ; Xiao, Wen-Hai ; Wang, Ying ; Zhou, Xiao ; Liu, Hong ; Li, Xia ; Ding, Ming-Zhu ; Liu, Duo ; Zhang, Lu ; Liu, Bao-Li ; Wu, Xiao-Le ; Li, Fei-Fei ; Dong, Xiu-Tao ; Jia, Bin ; Zhang, Wen-Zheng ; Jiang, Guo-Zhen ; Liu, Yue ; Bai, Xue ; Song, Tian-Qing ; Chen, Yan ; Zhou, Si-Jie ; Zhu, Rui-Ying ; Gao, Feng ; Kuang, Zheng ; Wang, Xuya ; Shen, Michael ; Yang, Kun ; Stracquadanio, Giovanni ; Richardson, Sarah M. ; Lin, Yicong ; Wang, Lihui ; Walker, Roy ; Luo, Yisha ; Ma, Ping-Sheng ; Yang, Huanming ; Cai, Yizhi ; Dai, Junbiao ; Bader, Joel S. ; Boeke, Jef D. ; Yuan, Ying-Jin. / Bug mapping and fitness testing of chemically synthesized chromosome X. In: Science. 2017 ; Vol. 355, No. 6329. pp. 1-6.

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title = "Bug mapping and fitness testing of chemically synthesized chromosome X",

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.",

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

year = "2017",

month = mar,

day = "10",

doi = "10.1126/science.aaf4706",

language = "English",

volume = "355",

pages = "1--6",

journal = "Science (New York, N.Y.)",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6329",

}

Wu, Y, Li, B-Z, Zhao, M, Mitchell, LA, Xie, Z-X, Lin, Q-H, Wang, X, Xiao, W-H, Wang, Y, Zhou, X, Liu, H, Li, X, Ding, M-Z, Liu, D, Zhang, L, Liu, B-L, Wu, X-L, Li, F-F, Dong, X-T, Jia, B, Zhang, W-Z, Jiang, G-Z, Liu, Y, Bai, X, Song, T-Q, Chen, Y, Zhou, S-J, Zhu, R-Y, Gao, F, Kuang, Z, Wang, X, Shen, M, Yang, K, Stracquadanio, G, Richardson, SM, Lin, Y, Wang, L, Walker, R, Luo, Y, Ma, P-S, Yang, H, Cai, Y, Dai, J, Bader, JS, Boeke, JD & Yuan, Y-J 2017, 'Bug mapping and fitness testing of chemically synthesized chromosome X', Science, vol. 355, no. 6329, eaaf4706, pp. 1-6. https://doi.org/10.1126/science.aaf4706

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

In: Science, Vol. 355, No. 6329, eaaf4706, 10.03.2017, p. 1-6.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Bug mapping and fitness testing of chemically synthesized chromosome X

AU - Wu, Yi

AU - Li, Bing-Zhi

AU - Zhao, Meng

AU - Mitchell, Leslie A.

AU - Xie, Ze-Xiong

AU - Lin, Qiu-Hui

AU - Wang, Xia

AU - Xiao, Wen-Hai

AU - Wang, Ying

AU - Zhou, Xiao

AU - Liu, Hong

AU - Li, Xia

AU - Ding, Ming-Zhu

AU - Liu, Duo

AU - Zhang, Lu

AU - Liu, Bao-Li

AU - Wu, Xiao-Le

AU - Li, Fei-Fei

AU - Dong, Xiu-Tao

AU - Jia, Bin

AU - Zhang, Wen-Zheng

AU - Jiang, Guo-Zhen

AU - Liu, Yue

AU - Bai, Xue

AU - Song, Tian-Qing

AU - Chen, Yan

AU - Zhou, Si-Jie

AU - Zhu, Rui-Ying

AU - Gao, Feng

AU - Kuang, Zheng

AU - Wang, Xuya

AU - Shen, Michael

AU - Yang, Kun

AU - Stracquadanio, Giovanni

AU - Richardson, Sarah M.

AU - Lin, Yicong

AU - Wang, Lihui

AU - Walker, Roy

AU - Luo, Yisha

AU - Ma, Ping-Sheng

AU - Yang, Huanming

AU - Cai, Yizhi

AU - Dai, Junbiao

AU - Bader, Joel S.

AU - Boeke, Jef D.

AU - Yuan, Ying-Jin

PY - 2017/3/10

Y1 - 2017/3/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85014820348&partnerID=8YFLogxK

U2 - 10.1126/science.aaf4706

DO - 10.1126/science.aaf4706

M3 - Article

C2 - 28280152

AN - SCOPUS:85014820348

VL - 355

SP - 1

EP - 6

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

SN - 0036-8075

IS - 6329

M1 - eaaf4706

ER -

Bug mapping and fitness testing of chemically synthesized chromosome X

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