BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, Guangdong, China; BGI-Shenzhen, Shenzhen 518083, Guangdong, China; China National Genebank, BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
BGI-Shenzhen, Shenzhen 518083, Guangdong, China; China National Genebank, BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Virus Res. 2018 Mar 2;247:71-83. doi: 10.1016/j.virusres.2018.01.014. Epub 2018 Feb 8.
A comprehensive demonstration of Zika virus (ZIKV) molecular evolution is essential for understanding its adaptation and expansion in its recent pandemics. Despite several studies on mutations and codon usage in ZIKVs, the variations in codon usage patterns across individual genes and their biological implication remains unclear. Here, we performed a gene-by-gene comparison of the codon usage variation in ZIKVs of the African and Asian lineages. We found that besides the evidence of positive selection (Ka/Ks >1) in the Asian lineage of the ZIKV genome, codon usage patterns were gene-specific and codon usage variation of ZIKV genes, was possibly constrained by their individual functional features, such as transmembrane domains, or antigenicity. In particular, the NS2B and NS4A genes showed distinct codon usage patterns, clearly separating them from the clusters of other genes in the correspondence analysis (CA). In the Asian lineage, the NS2B and NS4A genes showed the highest codon usage bias (ENC values: 51.01 ± 0.72 and 48.89 ± 0.99 respectively), and were subjected to the highest translation selection (ENC/ENC ratio: 0.847 ± 0.0297 and 0.828 ± 0.0233 respectively) in comparison to the African lineages of ZIKV. The CpG frequency of the NS2B showed a gradual ascending trend in the Asian ZIKV lineages, while in NS4A it was constrained along with the expansion of the Asian lineage. Furthermore, between the African and Asian lineages, differentiated and specific over-represented codons were more prominent in the NS2B and NS4A. Together, our study implies that ZIKVs are in the process of evolutionary fine tuning their codon as seen in the recent pandemics, and NS2B and NS4A could have played a potential role in the molecular evolution of the Asian lineage and their establishment.
全面展示寨卡病毒（ZIKV）分子进化对于理解其在最近的大流行中的适应性和扩张至关重要。尽管已经有几项关于 ZIKV 突变和密码子使用的研究，但个别基因的密码子使用模式的变化及其生物学意义仍不清楚。在这里，我们对来自非洲和亚洲谱系的 ZIKV 进行了逐个基因的密码子使用变化比较。我们发现，除了在 ZIKV 基因组的亚洲谱系中存在正选择（Ka/Ks>1）的证据外，密码子使用模式是基因特异性的，并且 ZIKV 基因的密码子使用变化可能受到其各自功能特征的限制，例如跨膜结构域或抗原性。特别是，NS2B 和 NS4A 基因表现出明显不同的密码子使用模式，在对应分析（CA）中清楚地将它们与其他基因的聚类区分开来。在亚洲谱系中，NS2B 和 NS4A 基因显示出最高的密码子使用偏好（ENC 值：分别为 51.01±0.72 和 48.89±0.99），并且与 ZIKV 的非洲谱系相比，它们受到最高的翻译选择（ENC/ENC 比：分别为 0.847±0.0297 和 0.828±0.0233）。NS2B 的 CpG 频率在亚洲 ZIKV 谱系中呈逐渐上升趋势，而在 NS4A 中则随着亚洲谱系的扩展而受到限制。此外，在非洲和亚洲谱系之间，分化和特异性过表达的密码子在 NS2B 和 NS4A 中更为突出。总之，我们的研究表明，寨卡病毒在最近的大流行中正在对其密码子进行进化微调，NS2B 和 NS4A 可能在亚洲谱系的分子进化及其建立中发挥了潜在作用。
