A self-propagating, barcoded transposon system for the dynamic rewiring of genomic networks.

IF 8.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Max A English, Miguel A Alcantar, James J Collins
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引用次数: 1

Abstract

In bacteria, natural transposon mobilization can drive adaptive genomic rearrangements. Here, we build on this capability and develop an inducible, self-propagating transposon platform for continuous genome-wide mutagenesis and the dynamic rewiring of gene networks in bacteria. We first use the platform to study the impact of transposon functionalization on the evolution of parallel Escherichia coli populations toward diverse carbon source utilization and antibiotic resistance phenotypes. We then develop a modular, combinatorial assembly pipeline for the functionalization of transposons with synthetic or endogenous gene regulatory elements (e.g., inducible promoters) as well as DNA barcodes. We compare parallel evolutions across alternating carbon sources and demonstrate the emergence of inducible, multigenic phenotypes and the ease with which barcoded transposons can be tracked longitudinally to identify the causative rewiring of gene networks. This work establishes a synthetic transposon platform that can be used to optimize strains for industrial and therapeutic applications, for example, by rewiring gene networks to improve growth on diverse feedstocks, as well as help address fundamental questions about the dynamic processes that have sculpted extant gene networks.

Abstract Image

Abstract Image

Abstract Image

一个自我繁殖的条形码转座子系统,用于基因组网络的动态重新布线。
在细菌中,自然转座子的调动可以驱动适应性基因组重排。在此,我们以这种能力为基础,开发了一种可诱导的、自繁殖的转座子平台,用于细菌中连续的全基因组诱变和基因网络的动态重连接。我们首先利用该平台研究了转座子功能化对平行大肠杆菌种群向不同碳源利用和抗生素抗性表型进化的影响。然后,我们开发了一个模块化的组合组装管道,用于用合成或内源性基因调控元件(例如,诱导启动子)以及DNA条形码实现转座子的功能化。我们比较了交替碳源的平行进化,并证明了可诱导的多基因表型的出现,以及条形码转座子可以纵向追踪以识别基因网络的致病重新连接的便性。这项工作建立了一个合成转座子平台,可用于优化用于工业和治疗应用的菌株,例如,通过重新连接基因网络以改善不同原料的生长,以及帮助解决有关塑造现有基因网络的动态过程的基本问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Systems Biology
Molecular Systems Biology 生物-生化与分子生物学
CiteScore
18.50
自引率
1.00%
发文量
62
审稿时长
6-12 weeks
期刊介绍: Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems. Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.
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