Efficient translation initiation dictates codon usage at gene start
Efficient translation initiation dictates codon usage at gene start
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DOI：
10.1038/msb.2013.32
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发表时间：
2013-06-01
影响因子：
9.9
通讯作者：
Bluethgen, Nils
中科院分区：
文献类型：
--
作者：
Bentele, Kajetan;Saffert, Paul;Bluethgen, Nils
遗传密码是简并的;因此，蛋白质进化并不唯一地决定编码序列。因此，进化遗传学的难题之一是揭示导致特定密码子选择的进化驱动力。在许多细菌中，蛋白质编码基因的前5-10个密码子通常是在基因组其余部分中使用频率较低的密码子，这种效应被认为是由于选择减缓早期延伸以减少核糖体交通堵塞而产生的。然而，许多物种的基因组分析表明，该区域显示出减少的mRNA折叠与有效翻译起始的压力一致。这提出了一种可能性，即不寻常的密码子使用是选择减少mRNA结构的副作用。在这里，我们区分这两个相互竞争的假设，并表明，在细菌的选择有利于密码子，减少mRNA折叠周围的翻译开始，无论这些密码子是频繁或罕见的。实验证实，主要是mRNA的结构，而不是密码子的使用，在基因的开始决定翻译速率。
The genetic code is degenerate; thus, protein evolution does not uniquely determine the coding sequence. One of the puzzles in evolutionary genetics is therefore to uncover evolutionary driving forces that result in specific codon choice. In many bacteria, the first 5-10 codons of protein-coding genes are often codons that are less frequently used in the rest of the genome, an effect that has been argued to arise from selection for slowed early elongation to reduce ribosome traffic jams. However, genome analysis across many species has demonstrated that the region shows reduced mRNA folding consistent with pressure for efficient translation initiation. This raises the possibility that unusual codon usage is a side effect of selection for reduced mRNA structure. Here we discriminate between these two competing hypotheses, and show that in bacteria selection favours codons that reduce mRNA folding around the translation start, regardless of whether these codons are frequent or rare. Experiments confirm that primarily mRNA structure, and not codon usage, at the beginning of genes determines the translation rate.