Genome landscapes and bacteriophage codon usage.
Genome landscapes and bacteriophage codon usage.
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DOI：
10.1371/journal.pcbi.1000001
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发表时间：
2008-02-29
影响因子：
4.3
通讯作者：
Plotkin JB
中科院分区：
文献类型：
--
作者：
Lucks JB;Nelson DR;Kudla GR;Plotkin JB
在生物生命的所有领域中，蛋白质编码基因表现出同义密码子的不平等使用。虽然替代理论比比皆是，翻译选择已被接受为一个重要的机制，在原核生物和简单的真核生物的密码子使用模式的形状。在这里，我们分析了感染大肠杆菌的74种不同噬菌体的密码子使用模式。大肠杆菌、铜绿假单胞菌和L.乳酸菌作为主要宿主。我们使用“基因组景观”的概念，这有助于揭示整个基因组中密码子使用的非平凡的长距离模式。我们开发了一系列随机化测试，使我们能够询问密码子使用的一个方面的意义，如GC含量，同时控制另一个方面，如适应宿主偏好的密码子。我们发现，33噬菌体基因组表现出高度非随机模式，在其GC 3含量，使用主机偏好的密码子，或两者兼而有之。我们表明，这些噬菌体的头部和尾部蛋白质表现出显着的偏向主机偏好的密码子，相对于非结构噬菌体蛋白。我们的研究结果支持的假设，翻译选择病毒基因的宿主偏好的密码子，在广泛的噬菌体。任何蛋白质都可以由多种同义拼写编码。但是生物体通常更喜欢一种拼写而不是另一种，这种现象被称为密码子偏好。密码子偏好通常被理解为是由于选择同义拼写而导致的，其增加了蛋白质翻译的速率和准确性。在这项工作中，我们检查了所有感染大肠杆菌的测序病毒的完整基因组。大肠杆菌、铜绿假单胞菌和L. lactis，并且已经发现这些病毒基因组中的许多也表现出密码子偏好性。此外，密码子偏好的程度在病毒基因组中是不同的，如使用称为“基因组景观”的技术所可视化的。通过比较观察到的基因组随机抽取的基因组，我们表明，在这些病毒基因组中的高密码子偏好的区域往往与编码结构蛋白的区域相一致。因此，病毒需要以高拷贝数产生的蛋白质利用与其宿主生物体对于高表达蛋白质所利用的相同编码。我们的研究结果将密码子偏好的翻译理论扩展到病毒界：病毒基因组的部分被选择以服从其宿主的偏好。
Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonymous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa, and L. lactis as their primary host. We use the concept of a “genome landscape,” which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such as GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages. Any protein can be encoded by multiple, synonymous spellings. But organisms typically prefer one spelling over another—a phenomenon known as codon bias. Codon bias is generally understood to result from selection for synonymous spellings that increase the rate and accuracy of protein translation. In this work, we have examined the complete genomes of all sequenced viruses that infect the bacteria E. coli, P. aeruginosa, and L. lactis, and have found that many of these viral genomes also exhibit codon bias. Moreover, the degree of codon bias varies across the viral genome, as visualized using a technique called a “genome landscape.” By comparing the observed genomes to randomly drawn genomes, we demonstrate that the regions of high codon bias in these viral genomes often coincide with regions encoding structural proteins. Thus, the proteins that a virus needs to produce in high copy number utilize the same encoding as its host organism does for highly expressed proteins. Our results extend the translational theory of codon bias to the viral kingdom: parts of the viral genome are selected to obey the preferences of its host.
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