Clustering of Codons with Rare Cognate tRNAs in Human Genes Suggests an Extra Level of Expression Regulation
Clustering of Codons with Rare Cognate tRNAs in Human Genes Suggests an Extra Level of Expression Regulation
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DOI：
10.1371/journal.pgen.1000548
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发表时间：
2009-07-01
期刊：
影响因子：
4.5
通讯作者：
Huynen, Martijn A.
中科院分区：
文献类型：
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作者：
Parmley, Joanna L.;Huynen, Martijn A.
在具有大的有效群体大小的物种中，高表达的基因倾向于由具有高度丰富的同源tRNA的密码子编码，以最大化翻译速率。然而，在高表达的人类基因中，几乎没有证据表明同义密码子存在类似的偏好。在这里，我们要问的是，是否有证据表明选择与低丰度tRNA相关的密码子。我们不是对完整基因的密码子使用进行平均，而是扫描具有偏离密码子使用的窗口的基因。我们发现，有一个显着的人类基因，包含低丰度同源tRNA的密码子簇的代表性。我们将这些区域命名为RTS（罕见tRNA评分）簇，与基因的其余部分相比，这些区域平均具有50%的同源tRNA可用量。我们观察到一个显着减少的替代率之间的人类RTS集群和他们的orthopathic黑猩猩序列相比，非RTS集群序列。总体而言，具有RTS簇的基因比非RTS簇基因具有更高的组织特异性。此外，这些基因在转录调控方面功能丰富。由于已知在低等真核生物中调节转录的基因参与按需翻译，这表明翻译水平表达调节的机制也存在于人类基因组中。
In species with large effective population sizes, highly expressed genes tend to be encoded by codons with highly abundant cognate tRNAs to maximize translation rate. However, there has been little evidence for a similar bias of synonymous codons in highly expressed human genes. Here, we ask instead whether there is evidence for the selection for codons associated with low abundance tRNAs. Rather than averaging the codon usage of complete genes, we scan the genes for windows with deviating codon usage. We show that there is a significant over representation of human genes that contain clusters of codons with low abundance cognate tRNAs. We name these regions, which on average have a 50% reduction in the amount of cognate tRNA available compared to the remainder of the gene, RTS (rare tRNA score) clusters. We observed a significant reduction in the substitution rate between the human RTS clusters and their orthologous chimp sequence, when compared to non-RTS cluster sequences. Overall, the genes with an RTS cluster have higher tissue specificity than the non-RTS cluster genes. Furthermore, these genes are functionally enriched for transcription regulation. As genes that regulate transcription in lower eukaryotes are known to be involved in translation on demand, this suggests that the mechanism of translation level expression regulation also exists within the human genome.