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Virus Res. 2018 Mar 2;247:71-83. doi: 10.1016/j.virusres.2018.01.014. Epub 2018 Feb 8.

Codon usage variation of Zika virus: The potential roles of NS2B and NS4A in its global pandemic.

Author information

1
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. Electronic address: lindechun@genomics.cn.
2
BGI-Shenzhen, Shenzhen 518083, Guangdong, China; China National Genebank, BGI-Shenzhen, Shenzhen 518083, Guangdong, China. Electronic address: liliqiang@genomics.cn.
3
Department of Pathogen Biology, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address: jimmy198360@163.com.
4
Department of Pathogen Biology, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address: 2150071@i.smu.edu.cn.
5
BGI-Shenzhen, Shenzhen 518083, Guangdong, China; China National Genebank, BGI-Shenzhen, Shenzhen 518083, Guangdong, China. Electronic address: saksenanitinkumar@genomics.cn.
6
The School of Foreign Studies, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address: fanglan@fimmu.com.
7
Department of Pathogen Biology, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address: wal034@ucsd.edu.
8
Department of Pathogen Biology, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address: daigeyang@fimmu.com.
9
BGI-Shenzhen, Shenzhen 518083, Guangdong, China; China National Genebank, BGI-Shenzhen, Shenzhen 518083, Guangdong, China; Department of Biology, University of Copenhagen, Copenhagen, Denmark. Electronic address: majinmin@genomics.cn.
10
Department of Pathogen Biology, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address: zhouxh@fimmu.com.
11
Department of Pathogen Biology, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address: xgchen2001@hotmail.com.

Abstract

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 (ENCobs/ENCexp 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.

KEYWORDS:

Codon usage bias; NS2B; NS4A; The African and Asian lineages; Zika virus

PMID:
29428601
DOI:
10.1016/j.virusres.2018.01.014
[Indexed for MEDLINE]

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