Characterization of accessory genes in coronavirus genomes
Characterization of accessory genes in coronavirus genomes
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DOI：
10.1186/s12985-020-01402-1
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发表时间：
2020-08-27
期刊：
影响因子：
4.8
通讯作者：
Thompson, Julie Dawn
中科院分区：
文献类型：
--
作者：
Michel, Christian Jean;Mayer, Claudine;Thompson, Julie Dawn
covid - 19感染是由冠状病毒（CoV）家族的新成员SARS-CoV-2病毒引起的。冠状病毒基因组编码ORF1a / ORF1ab多蛋白和四种结构蛋白，这些蛋白被广泛研究为主要的药物靶点。基因组还包含可变数量的开放阅读框（orf），编码辅助蛋白，这些蛋白对病毒复制不是必需的，但似乎在发病机制中起作用。辅助蛋白的特征较少，难以用经典的生物信息学方法进行预测。方法我们提出了一个计算工具GOFIX来表征病毒基因组中潜在的orf。特别是，ORF编码潜力是通过寻找xcircular编码基序的富集来估计的，已知该基序在病毒基因的阅读框中被过度代表。结果应用GOFIX对蝙蝠、果子狸和穿山甲宿主的SARS-CoV-2及其相关基因组（包括SARS-CoV和sars样病毒）进行了研究，重点研究了辅助蛋白。我们的分析提供了证据支持在所有基因组中存在重叠的orf 7b， 9b和9c，从而有助于解决当前基因组注释的一些差异。相反，我们预测ORF3b并不是在所有基因组中都起作用。还预测了新的假定ORF，包括先前在SARS-CoV-2中发现的ORF10的截断形式，以及在果子狸- cov和SARS-CoV中与Spike蛋白重叠的鲜为人知的ORF。结论我们的发现有助于表征SARS冠状病毒附属基因的序列特性，特别是新获得的基因利用重叠阅读框。
Background The Covid19 infection is caused by the SARS-CoV-2 virus, a novel member of the coronavirus (CoV) family. CoV genomes code for a ORF1a / ORF1ab polyprotein and four structural proteins widely studied as major drug targets. The genomes also contain a variable number of open reading frames (ORFs) coding for accessory proteins that are not essential for virus replication, but appear to have a role in pathogenesis. The accessory proteins have been less well characterized and are difficult to predict by classical bioinformatics methods. Methods We propose a computational tool GOFIX to characterize potential ORFs in virus genomes. In particular, ORF coding potential is estimated by searching for enrichment in motifs of theXcircular code, that is known to be over-represented in the reading frames of viral genes. Results We applied GOFIX to study the SARS-CoV-2 and related genomes including SARS-CoV and SARS-like viruses from bat, civet and pangolin hosts, focusing on the accessory proteins. Our analysis provides evidence supporting the presence of overlapping ORFs 7b, 9b and 9c in all the genomes and thus helps to resolve some differences in current genome annotations. In contrast, we predict that ORF3b is not functional in all genomes. Novel putative ORFs were also predicted, including a truncated form of the ORF10 previously identified in SARS-CoV-2 and a little known ORF overlapping the Spike protein in Civet-CoV and SARS-CoV. Conclusions Our findings contribute to characterizing sequence properties of accessory genes of SARS coronaviruses, and especially the newly acquired genes making use of overlapping reading frames.