Design and synthesis of a minimal bacterial genome

被引:903
作者
Hutchison, Clyde A., III [1 ]
Chuang, Ray-Yuan [1 ,5 ]
Noskov, Vladimir N. [1 ]
Assad-Garcia, Nacyra [1 ]
Deerinck, Thomas J. [2 ]
Ellisman, Mark H. [2 ]
Gill, John [3 ]
Kannan, Krishna [3 ]
Karas, Bogumil J. [1 ]
Ma, Li [1 ]
Pelletier, James F. [4 ,6 ]
Qi, Zhi-Qing [3 ]
Richter, R. Alexander [1 ]
Strychalski, Elizabeth A. [4 ]
Sun, Lijie [1 ,7 ]
Suzuki, Yo [1 ]
Tsvetanova, Billyana [3 ]
Wise, Kim S. [1 ]
Smith, Hamilton O. [1 ,3 ]
Glass, John I. [1 ]
Merryman, Chuck [1 ]
Gibson, Daniel G. [1 ,3 ]
Venter, J. Craig [1 ,3 ]
机构
[1] J Craig Venter Inst, La Jolla, CA 92037 USA
[2] Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, La Jolla, CA 92037 USA
[3] Synthet Genom, La Jolla, CA 92037 USA
[4] NIST, Gaithersburg, MD 20899 USA
[5] Amer Type Culture Collect, 10801 Univ Blvd, Manassas, VA 20110 USA
[6] MIT, Ctr Bits & Atoms, Room E15-401,20 Ames St, Cambridge, MA 02139 USA
[7] CBRITE, 11575 Sorrento Valley Rd,Suite 204, San Diego, CA 92121 USA
关键词
ESSENTIAL GENES; MYCOPLASMA; SEPF;
D O I
10.1126/science.aad6253
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We used whole-genome design and complete chemical synthesis to minimize the 1079-kilobase pair synthetic genome of Mycoplasma mycoides JCVI-syn1.0. An initial design, based on collective knowledge of molecular biology combined with limited transposon mutagenesis data, failed to produce a viable cell. Improved transposon mutagenesis methods revealed a class of quasi-essential genes that are needed for robust growth, explaining the failure of our initial design. Three cycles of design, synthesis, and testing, with retention of quasi-essential genes, produced JCVI-syn3.0 (531 kilobase pairs, 473 genes), which has a genome smaller than that of any autonomously replicating cell found in nature. JCVI-syn3.0 retains almost all genes involved in the synthesis and processing of macromolecules. Unexpectedly, it also contains 149 genes with unknown biological functions. JCVI-syn3.0 is a versatile platform for investigating the core functions of life and for exploring whole-genome design.
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页数:11
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