Molecular Evolution of Protein Sequences and Codon Usage in Monkeypox Viruses

IF 11.5 2区 生物学 Q1 GENETICS & HEREDITY
Ke-jia Shan, Changcheng Wu, Xiaolu Tang, Roujian Lu, Yaling Hu, Wenjie Tan, Jian Lu
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Abstract The monkeypox virus (mpox virus, MPXV) epidemic in 2022 has posed a significant public health risk. Yet, the evolutionary principles of MPXV remain largely unknown. Here, we examined the evolutionary patterns of protein sequences and codon usage in MPXV. We first demonstrated the signal of positive selection in OPG027, specifically in the Clade I lineage of MPXV. Subsequently, we discovered accelerated protein sequence evolution over time in the variants responsible for the 2022 outbreak. Furthermore, we showed strong epistasis between amino acid substitutions located in different genes. The codon adaptation index (CAI) analysis revealed that MPXV genes tended to use more non-preferred codons compared to human genes, and the CAI decreased over time and diverged between clades, with Clade I &gt; IIa and IIb-A &gt; IIb-B. While the decrease in fatality rate among the three groups aligned with the CAI pattern, it remains unclear whether this correlation was coincidental or if the deoptimization of codon usage in MPXV led to a reduction in fatality rates. This study sheds new light on the mechanisms that govern the evolution of MPXV in human populations.
猴痘病毒蛋白质序列和密码使用的分子进化
摘要 2022 年流行的猴痘病毒(monkeypox virus,MPXV)对公众健康构成了重大威胁。然而,MPXV的进化原理在很大程度上仍然未知。在此,我们研究了MPXV中蛋白质序列和密码子使用的进化模式。我们首先证明了 OPG027 中的正选择信号,特别是在 MPXV 的支系 I 中。随后,我们发现在造成 2022 年疫情爆发的变体中,蛋白质序列随时间加速进化。此外,我们还发现位于不同基因中的氨基酸替代之间存在很强的外显性。密码子适应指数(CAI)分析表明,与人类基因相比,MPXV基因倾向于使用更多的非首选密码子,CAI随时间推移而降低,并在支系之间出现分化,支系I&gt;IIa和支系IIb-A&gt;IIb-B。虽然这三个类群的死亡率下降与 CAI 模式一致,但目前还不清楚这种相关性是巧合还是 MPXV 中密码子使用的非优化导致了死亡率的下降。这项研究为人类中 MPXV 的进化机制提供了新的线索。
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来源期刊
Genomics, Proteomics & Bioinformatics
Genomics, Proteomics & Bioinformatics Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
14.30
自引率
4.20%
发文量
844
审稿时长
61 days
期刊介绍: Genomics, Proteomics and Bioinformatics (GPB) is the official journal of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China. It aims to disseminate new developments in the field of omics and bioinformatics, publish high-quality discoveries quickly, and promote open access and online publication. GPB welcomes submissions in all areas of life science, biology, and biomedicine, with a focus on large data acquisition, analysis, and curation. Manuscripts covering omics and related bioinformatics topics are particularly encouraged. GPB is indexed/abstracted by PubMed/MEDLINE, PubMed Central, Scopus, BIOSIS Previews, Chemical Abstracts, CSCD, among others.
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