复制子
复制(统计)
突变体
遗传学
突变率
大肠杆菌
聚合酶
功能(生物学)
DNA聚合酶
突变
生物
DNA复制
基因组
计算生物学
DNA
分子生物学
细胞生物学
基因
病毒学
作者
Rongzhen Tian,Fabian B. H. Rehm,Dariusz Czernecki,Yangqi Gu,Jérôme F. Zürcher,Kim C. Liu,Jason W. Chin
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2024-01-26
卷期号:383 (6681): 421-426
被引量:5
标识
DOI:10.1126/science.adk1281
摘要
The evolution of new function in living organisms is slow and fundamentally limited by their critical mutation rate. Here, we established a stable orthogonal replication system in Escherichia coli. The orthogonal replicon can carry diverse cargos of at least 16.5 kilobases and is not copied by host polymerases but is selectively copied by an orthogonal DNA polymerase (O-DNAP), which does not copy the genome. We designed mutant O-DNAPs that selectively increase the mutation rate of the orthogonal replicon by two to four orders of magnitude. We demonstrate the utility of our system for accelerated continuous evolution by evolving a 150-fold increase in resistance to tigecycline in 12 days. And, starting from a GFP variant, we evolved a 1000-fold increase in cellular fluorescence in 5 days.
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