Ozaki Keita, Matsushima Yuki, Nagasawa Koo, Aso Jumpei, Saraya Takeshi, Yoshihara Keisuke, Murakami Koichi, Motoya Takumi, Ryo Akihide, Kuroda Makoto, Katayama Kazuhiko, Kimura Hirokazu
Graduate School of Health Sciences, Gunma Paz University, Takasaki, Japan.
Niitaka Co., Ltd., Osaka, Japan.
Front Microbiol. 2020 Jan 14;10:2991. doi: 10.3389/fmicb.2019.02991. eCollection 2019.
Noroviruses are a major cause of viral epidemic gastroenteritis in humans worldwide. The protease (Pro) encoded in open reading frame 1 (ORF1) is an essential enzyme for proteolysis of the viral polyprotein. Although there are some reports regarding the evolutionary analysis of norovirus GII-encoding genes, there are few reports focused on the region. We analyzed the molecular evolution of the region of norovirus GII using bioinformatics approaches. A time-scaled phylogenetic tree of the region constructed using a Bayesian Markov chain Monte Carlo method indicated that the common ancestor of GII diverged from GIV around 1680 CE [95% highest posterior density (HPD), 1607-1749]. The GII region emerged around 1752 CE (95%HPD, 1707-1794), forming three further lineages. The evolutionary rate of GII region was estimated at more than 10 substitutions/site/year. The distribution of the phylogenetic distances of each genotype differed, and showed genetic diversity. Mapping of the negative selection and substitution sites of the Pro structure showed that the substitution sites in the Pro protein were mostly produced under neutral selection in positions structurally adjacent to the active sites for proteolysis, whereas negative selection was observed in residues distant from the active sites. The phylodynamics of GII.P4, GII.P7, GII.P16, GII.P21, and GII.P31 indicated that their effective population sizes increased during the period from 2005 to 2016 and the increase in population size was almost consistent with the collection year of these genotypes. These results suggest that the region of the norovirus GII evolved rapidly, but under no positive selection, with a high genetic divergence, similar to that of the RNA-dependent RNA polymerase () region and the region of noroviruses.
诺如病毒是全球人类病毒性流行性肠胃炎的主要病因。开放阅读框1（ORF1）中编码的蛋白酶（Pro）是病毒多聚蛋白进行蛋白水解的必需酶。尽管有一些关于诺如病毒GII编码基因进化分析的报道，但针对该区域的报道较少。我们使用生物信息学方法分析了诺如病毒GII该区域的分子进化。使用贝叶斯马尔可夫链蒙特卡罗方法构建的该区域的时间尺度系统发育树表明，GII的共同祖先在公元1680年左右（95%最高后验密度（HPD），1607 - 1749）与GIV分化。GII该区域在公元1752年左右出现（9%HPD，1707 - 1794），形成了另外三个谱系。GII该区域的进化速率估计超过10个替换/位点/年。每种基因型的系统发育距离分布不同，并显示出遗传多样性。Pro结构的负选择和替换位点图谱显示，Pro蛋白中的替换位点大多在结构上与蛋白水解活性位点相邻的位置处于中性选择下产生，而在远离活性位点的残基中观察到负选择。GII.P4、GII.P7、GII.P16、GII.P21和GII.P31的系统发育动力学表明，它们的有效种群大小在2005年至2016年期间增加，种群大小的增加几乎与这些基因型的收集年份一致。这些结果表明诺如病毒GII的该区域进化迅速，但没有正选择，具有高遗传分化，类似于诺如病毒的RNA依赖性RNA聚合酶（RdRp）区域和该区域。
