Abstract:
Negative sense RNA viruses (NSV) include some of the most detrimental human pathogens, including the influenza, Ebola, and measles viruses. NSV genomes consist of one or multiple single-stranded RNA molecules that are encapsidated into one or more ribonucleoprotein (RNP) complexes. These RNPs consist of viral RNA, a viral RNA polymerase, and many copies of the viral nucleoprotein (NP). Current evolutionary relationships within the NSV phylum are based on the alignment of conserved RNA-dependent RNA polymerase (RdRp) domain amino acid sequences. However, the RdRp domain-based phylogeny does not address whether NP, the other core protein in the NSV genome, evolved along the same trajectory or whether several RdRp-NP pairs evolved through convergent evolution in the segmented and non-segmented NSV genome architectures. Addressing how NP and the RdRp domain evolved may help us better understand NSV diversity. Since NP sequences are too short to infer robust phylogenetic relationships, we here used experimentally obtained and AlphaFold 2.0-predicted NP structures to probe whether evolutionary relationships can be estimated using NSV NP sequences. Following flexible structure alignments of modeled structures, we find that the structural homology of the NSV NPs reveals phylogenetic clusters that are consistent with RdRp-based clustering. In addition, we were able to assign viruses for which RdRp sequences are currently missing to phylogenetic clusters based on the available NP sequence. Both our RdRp-based and NP-based relationships deviate from the current NSV classification of the segmented Naedrevirales, which cluster with the other segmented NSVs in our analysis. Overall, our results suggest that the NSV RdRp and NP genes largely evolved along similar trajectories and even short pieces of genetic, protein-coding information can be used to infer evolutionary relationships, potentially making metagenomic analyses more valuable.
摘要:
负义RNA病毒(NSV)包括一些最有害的人类病原体,包括流感,埃博拉病毒,和麻疹病毒。NSV基因组由一个或多个单链RNA分子组成,这些分子被包装成一个或多个核糖核蛋白(RNP)复合物。这些RNP由病毒RNA组成,病毒RNA聚合酶,和病毒核蛋白(NP)的许多拷贝。NSV门内的当前进化关系基于保守的RNA依赖性RNA聚合酶(RdRp)结构域氨基酸序列的比对。然而,基于RdRp域的系统发育没有解决NP,NSV基因组中的另一个核心蛋白,沿着相同的轨迹进化,或者几个RdRp-NP对是否通过分段和非分段NSV基因组架构中的趋同进化而进化。解决NP和RdRp域如何进化可能有助于我们更好地理解NSV多样性。由于NP序列太短,无法推断稳健的系统发育关系,我们在这里使用实验获得的和AlphaFold2.0预测的NP结构来探测是否可以使用NSVNP序列估计进化关系。根据建模结构的灵活结构对齐,我们发现NSVNP的结构同源性揭示了与基于RdRp的聚类一致的系统发育聚类。此外,我们能够根据现有的NP序列将目前缺少RdRp序列的病毒分配到系统发育簇.我们基于RdRp和基于NP的关系都偏离了当前NSV分类的分段Naedrevirales,在我们的分析中与其他分段的NSV聚类。总的来说,我们的结果表明,NSVRdRp和NP基因在很大程度上沿着相似的轨迹进化,甚至是短暂的遗传片段,蛋白质编码信息可以用来推断进化关系,可能使宏基因组分析更有价值。