Causes and Effects of N-Terminal Codon Bias in Bacterial Genes
Causes and Effects of N-Terminal Codon Bias in Bacterial Genes
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DOI：
10.1126/science.1241934
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发表时间：
2013-10-25
期刊：
影响因子：
56.9
通讯作者：
Kosuri, Sriram
中科院分区：
文献类型：
--
作者：
Goodman, Daniel B.;Church, George M.;Kosuri, Sriram
大多数氨基酸由多个密码子编码，密码子的选择对蛋白质表达有很大影响。在大多数生物体中，稀有密码子在基因的 N 末端富集，尽管这种偏差的原因和影响尚不清楚。在这里，我们测量了大肠杆菌中超过 14,000 个合成报告基因的表达，结果表明使用 N 端稀有密码子代替常见密码子可使表达增加约 14 倍（中位数 4 倍）。我们量化了单个 N 末端密码子如何影响表达，并表明这些影响塑造了自然基因的序列。最后，我们证明RNA结构的减少而不是密码子稀有性本身是表达增加的原因。我们的观察解决了关于 N 末端密码子偏倚作用的争议，并提出了一种优化细菌中异源基因表达的简单方法。
Most amino acids are encoded by multiple codons, and codon choice has strong effects on protein expression. Rare codons are enriched at the N terminus of genes in most organisms, although the causes and effects of this bias are unclear. Here, we measure expression from >14,000 synthetic reporters in Escherichia coli and show that using N-terminal rare codons instead of common ones increases expression by similar to 14-fold (median 4-fold). We quantify how individual N-terminal codons affect expression and show that these effects shape the sequence of natural genes. Finally, we demonstrate that reduced RNA structure and not codon rarity itself is responsible for expression increases. Our observations resolve controversies over the roles of N-terminal codon bias and suggest a straightforward method for optimizing heterologous gene expression in bacteria.