Codon usage suggests that translational selection has a major impact on protein expression in trypanosomatids
Codon usage suggests that translational selection has a major impact on protein expression in trypanosomatids
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DOI：
10.1186/1471-2164-9-2
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发表时间：
2008-01-03
期刊：
影响因子：
4.4
通讯作者：
Horn, David
中科院分区：
文献类型：
--
作者：
Horn, David
背景：构建一个活细胞需要不同数量的蛋白质。在大多数生物体中，转录控制对差异表达起着重要作用。在锥虫中，大多数基因在大的多顺反子群集中以相同的速率转录，但情况并非如此。因此，锥虫必须使用转录后控制机制来平衡基因表达需求。结果：本文探讨了翻译选择的证据，即在更多高表达基因中富集“有利”密码子。一组高表达、串联重复的基因在克氏锥虫、布鲁氏锥虫和大利什曼原虫中表现出密码子偏性。tRNA补体揭示了61个可能的反密码子中的45个，表明“摆动”tRNA的广泛使用。与翻译选择一致，有利密码子的同源tRNA基因被过度代表。重要的是，密码子的使用（密码子适应指数）与预测和观察到的表达水平相关。此外，在不同锥虫共体基因中，密码子的相对偏倚是广泛保守的。结论：同义密码子偏倚与锥虫tRNA基因拷贝数及蛋白表达水平相关。综上所述，这些结果表明，翻译选择是这些生物中差异蛋白表达控制的主要机制。这些发现揭示了锥虫如何弥补典型Pol II启动子的缺乏和随后广泛的组成性RNA聚合酶II转录。
Background: Different proteins are required in widely different quantities to build a living cell. In most organisms, transcription control makes a major contribution to differential expression. This is not the case in trypanosomatids where most genes are transcribed at an equivalent rate within large polycistronic clusters. Thus, trypanosomatids must use post-transcriptional control mechanisms to balance gene expression requirements.Results: Here, the evidence for translational selection, the enrichment of 'favoured' codons in more highly expressed genes, is explored. A set of highly expressed, tandem-repeated genes display codon bias in Trypanosoma cruzi, Trypanosoma brucei and Leishmania major. The tRNA complement reveals forty-five of the sixty-one possible anticodons indicating widespread use of 'wobble' tRNAs. Consistent with translational selection, cognate tRNA genes for favoured codons are over-represented. Importantly, codon usage (Codon Adaptation Index) correlates with predicted and observed expression level. In addition, relative codon bias is broadly conserved among syntenic genes from different trypanosomatids.Conclusion: Synonymous codon bias is correlated with tRNA gene copy number and with protein expression level in trypanosomatids. Taken together, the results suggest that translational selection is the dominant mechanism underlying the control of differential protein expression in these organisms. The findings reveal how trypanosomatids may compensate for a paucity of canonical Pol II promoters and subsequent widespread constitutive RNA polymerase II transcription.