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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Artificial gene amplification reveals an abundance of promiscuous resistance determinants in Escherichia coli
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Artificial gene amplification reveals an abundance of promiscuous resistance determinants in Escherichia coli

机译：人工基因扩增揭示了大肠杆菌中大量混杂的耐药决定簇

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Duplicated genes provide an important raw material for adaptive evolution. However, the relationship between gene duplication and the emergence of new biochemical functions is complicated, and it has been difficult to quantify the likelihood of evolving novelty in any systematic manner. Here, we describe a comprehensive search for artificially amplified genes that are able to impart new phenotypes on Escherichia coli, provided their expression is up-regulated. We used a high-throughput library-on-library strategy to screen for resistance to antibiotics and toxins. Cells containing a complete E. coli ORF library were exposed to 237 toxin-containing environments. From 86 of these environments, we identified a total of 115 cases where overexpressed ORFs imparted improved growth. Of the overexpressed ORFs that we tested, most conferred small but reproducible increases in minimum inhibitory concentration (≤ 16-fold) for their corresponding antibiotics. In many cases, proteins were acting promiscuously to impart resistance. In the absence of toxins, most strains bore no fitness cost associated with ORF overexpression. Our results show that even the genome of a nonpathogenic bacterium harbors a substantial reservoir of resistance genes, which can be readily accessed through overexpression mutations. During the growth of a population under selection, these mutations are most likely to be gene amplifications. Therefore, our work provides validation and biochemical insight into the innovation, amplification, and divergence model of gene evolution under continuous selection [Bergthorsson U, Andersson Dl, Roth JR (2007) Proc Natl Acad Sci USA 104:17004-17009], and also illustrates the high frequency at which novel traits can evolve in bacterial populations.
机译：复制的基因为适应性进化提供了重要的原材料。但是，基因复制和新的生化功能的出现之间的关系是复杂的，并且很难以任何系统的方式来量化发展新奇的可能性。在这里，我们描述了对人工扩增基因的全面搜索，只要它们的表达被上调，这些基因就可以在大肠杆菌上赋予新的表型。我们使用了高通量的库对库策略来筛选对抗生素和毒素的耐药性。将包含完整大肠杆菌ORF文库的细胞暴露于237种含毒素的环境中。从这些环境的86个中，我们总共鉴定出115个过度表达的ORF促进生长的病例。在我们测试的过表达的ORF中，大多数赋予其相应抗生素最小抑菌浓度（≤16倍）的微小但可重现的增加。在许多情况下，蛋白质混杂地发挥作用以赋予抵抗力。在没有毒素的情况下，大多数菌株不承担与ORF过表达相关的适应性费用。我们的结果表明，即使是非致病性细菌的基因组也具有大量的抗性基因库，可以通过过量表达突变轻易地获得这些基因。在所选种群的生长过程中，这些突变最有可能是基因扩增。因此，我们的工作为连续选择下基因进化的创新，扩增和发散模型提供了验证和生物化学见识[Bergthorsson U，Andersson Dl，Roth JR（2007）Proc Natl Acad Sci USA 104：17004-17009]，以及说明了在细菌种群中新特征可以进化的高频率。

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