Department of Biomedical Engineering, Tel-Aviv University, Ramat Aviv, Israel.
SynVaccineLtd. Ramat Hachayal, Tel Aviv, Israel.
BMC Genomics. 2017 Nov 13;18(1):866. doi: 10.1186/s12864-017-4248-7.
Viruses undergo extensive evolutionary selection for efficient replication which effects, among others, their codon distribution. In the current study, we aimed at understanding the way evolution shapes the codon distribution in early vs. late viral genes in terms of their expression during different stages in the viral replication cycle. To this end we analyzed 14 bacteriophages and 11 human viruses with available information about the expression phases of their genes.
We demonstrated evidence of selection for distinct composition of synonymous codons in early and late viral genes in 50% of the analyzed bacteriophages. Among others, this phenomenon may be related to the time specific adaptation of the viral genes to the translation efficiency factors involved at different bacteriophage developmental stages. Specifically, we showed that the differences in codon composition in different temporal gene groups cannot be explained only by phylogenetic proximities between the analyzed bacteriophages, and can be partially explained by differences in the adaptation to the host tRNA pool, nucleotide bias, GC content and more. In contrast, no difference in temporal regulation of synonymous codon usage was observed in human viruses, possibly because of a stronger selection pressure due to a larger effective population size in bacteriophages and their bacterial hosts.
The codon distribution in large fractions of bacteriophage genomes tend to be different in early and late genes. This phenomenon seems to be related to various aspects of the viral life cycle, and to various intracellular processes. We believe that the reported results should contribute towards better understanding of viral evolution and may promote the development of relevant procedures in synthetic virology.
病毒在复制过程中经历了广泛的进化选择,以提高其效率,这影响了它们的密码子分布。在本研究中,我们旨在从病毒复制周期不同阶段的表达角度,了解进化如何影响早期和晚期病毒基因的密码子分布。为此,我们分析了 14 种噬菌体和 11 种人类病毒,这些病毒的基因表达阶段都有相关信息。
我们证明了在 50%的分析噬菌体中,早期和晚期病毒基因的同义密码子组成存在选择的证据。其中,这种现象可能与病毒基因在不同噬菌体发育阶段对翻译效率因子的特定时间适应性有关。具体来说,我们表明,不同时间基因组之间密码子组成的差异不能仅通过分析噬菌体之间的系统发育关系来解释,部分可以通过对宿主 tRNA 池、核苷酸偏好性、GC 含量等的适应性差异来解释。相比之下,在人类病毒中,没有观察到同义密码子使用的时间调节差异,这可能是由于噬菌体及其细菌宿主的有效种群大小较大,因此选择压力更强。
噬菌体基因组的大部分区域中,早期和晚期基因的密码子分布倾向于不同。这种现象似乎与病毒生命周期的各个方面以及各种细胞内过程有关。我们相信,所报道的结果将有助于更好地理解病毒进化,并可能促进合成病毒学中相关程序的发展。