基因组
基因
生物
计算生物学
遗传学
终止密码子
遗传密码
作者
Nili Ostrov,Matthieu Landon,Marc Güell,Gleb Kuznetsov,Jun Teramoto,Natalie Cervantes,Minerva Zhou,Kerry Singh,Michael G. Napolitano,Mark Moosburner,Ellen Shrock,Benjamin W. Pruitt,Nicholas Conway,Daniel B. Goodman,Cameron L. Gardner,Gary Tyree,Alexandra S. Gonzales,Barry L. Wanner,Julie E. Norville,Marc J. Lajoie,George M. Church
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2016-08-19
卷期号:353 (6301): 819-822
被引量:243
标识
DOI:10.1126/science.aaf3639
摘要
Recoding--the repurposing of genetic codons--is a powerful strategy for enhancing genomes with functions not commonly found in nature. Here, we report computational design, synthesis, and progress toward assembly of a 3.97-megabase, 57-codon Escherichia coli genome in which all 62,214 instances of seven codons were replaced with synonymous alternatives across all protein-coding genes. We have validated 63% of recoded genes by individually testing 55 segments of 50 kilobases each. We observed that 91% of tested essential genes retained functionality with limited fitness effect. We demonstrate identification and correction of lethal design exceptions, only 13 of which were found in 2229 genes. This work underscores the feasibility of rewriting genomes and establishes a framework for large-scale design, assembly, troubleshooting, and phenotypic analysis of synthetic organisms.
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