Title |
Design and synthesis of a minimal bacterial genome
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Published in |
Science, March 2016
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DOI | 10.1126/science.aad6253 |
Pubmed ID | |
Authors |
Clyde A Hutchison, Ray-Yuan Chuang, Vladimir N Noskov, Nacyra Assad-Garcia, Thomas J Deerinck, Mark H Ellisman, John Gill, Krishna Kannan, Bogumil J Karas, Li Ma, James F Pelletier, Zhi-Qing Qi, R Alexander Richter, Elizabeth A Strychalski, Lijie Sun, Yo Suzuki, Billyana Tsvetanova, Kim S Wise, Hamilton O Smith, John I Glass, Chuck Merryman, Daniel G Gibson, J Craig Venter |
Abstract |
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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