{"title":"在 SARS-CoV-2 中,宿主依赖的 C 到 U RNA 编辑产生了具有优化表达能力的新型病毒基因。","authors":"Pirun Zhang, Wenli Zhang, Jiahuan Li, Huiying Liu, Yantong Yu, Xiaoping Yang, Wenqing Jiang","doi":"10.3389/fcimb.2024.1476605","DOIUrl":null,"url":null,"abstract":"<p><p>Rampant C-to-U RNA editing drives the mutation and evolution of SARS-CoV-2. While much attention has been paid to missense mutations, the C-to-U events leading to AUG and thus creating novel ORFs were uninvestigated. By utilizing the public time-course mutation data from the worldwide SARS-CoV-2 population, we systematically identified the \"AUG-gain mutations\" caused by C-to-U RNA editing. Synonymous mutations were of special focus. A total of 58 synonymous C-to-U sites are able to create out-of-frame AUG in coding sequence (CDS). These 58 synonymous sites showed significantly higher allele frequency (AF) and increasing rate (<i>d</i>AF/<i>d</i>t) than other C-to-U synonymous sites in the SARS-CoV-2 population, suggesting that these 58 AUG-gain events conferred additional benefits to the virus and are subjected to positive selection. The 58 predicted new ORFs created by AUG-gain events showed the following advantages compared to random expectation: they have longer lengths, higher codon adaptation index (CAI), higher Kozak scores, and higher tRNA adaptation index (tAI). The 58 putatively novel ORFs have high expressibility and are very likely to be functional, providing an explanation for the positive selection on the 58 AUG-gain mutations. Our study proposed a possible mechanism of the emergence of <i>de novo</i> genes in SARS-CoV-2. This idea should be helpful in studying the mutation and evolution of SARS-CoV-2.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496155/pdf/","citationCount":"0","resultStr":"{\"title\":\"Host-dependent C-to-U RNA editing in SARS-CoV-2 creates novel viral genes with optimized expressibility.\",\"authors\":\"Pirun Zhang, Wenli Zhang, Jiahuan Li, Huiying Liu, Yantong Yu, Xiaoping Yang, Wenqing Jiang\",\"doi\":\"10.3389/fcimb.2024.1476605\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Rampant C-to-U RNA editing drives the mutation and evolution of SARS-CoV-2. While much attention has been paid to missense mutations, the C-to-U events leading to AUG and thus creating novel ORFs were uninvestigated. By utilizing the public time-course mutation data from the worldwide SARS-CoV-2 population, we systematically identified the \\\"AUG-gain mutations\\\" caused by C-to-U RNA editing. Synonymous mutations were of special focus. A total of 58 synonymous C-to-U sites are able to create out-of-frame AUG in coding sequence (CDS). These 58 synonymous sites showed significantly higher allele frequency (AF) and increasing rate (<i>d</i>AF/<i>d</i>t) than other C-to-U synonymous sites in the SARS-CoV-2 population, suggesting that these 58 AUG-gain events conferred additional benefits to the virus and are subjected to positive selection. The 58 predicted new ORFs created by AUG-gain events showed the following advantages compared to random expectation: they have longer lengths, higher codon adaptation index (CAI), higher Kozak scores, and higher tRNA adaptation index (tAI). The 58 putatively novel ORFs have high expressibility and are very likely to be functional, providing an explanation for the positive selection on the 58 AUG-gain mutations. Our study proposed a possible mechanism of the emergence of <i>de novo</i> genes in SARS-CoV-2. This idea should be helpful in studying the mutation and evolution of SARS-CoV-2.</p>\",\"PeriodicalId\":12458,\"journal\":{\"name\":\"Frontiers in Cellular and Infection Microbiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496155/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Cellular and Infection Microbiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fcimb.2024.1476605\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cellular and Infection Microbiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fcimb.2024.1476605","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
猖獗的C-to-U RNA编辑推动了SARS-CoV-2的突变和进化。虽然人们对错义突变给予了很大关注,但对导致AUG从而产生新的ORF的C-to-U事件却没有进行研究。通过利用来自全球 SARS-CoV-2 群体的公开时间历程突变数据,我们系统地确定了由 C 到 U RNA 编辑引起的 "AUG-增益突变"。我们特别关注同义突变。共有 58 个同义 C-to-U 位点能够在编码序列(CDS)中产生框架外 AUG。在 SARS-CoV-2 群体中,这 58 个同义位点的等位基因频率(AF)和增殖率(dAF/dt)明显高于其他 C-to-U 同义位点,这表明这 58 个 AUG 增益事件给病毒带来了额外的益处,并受到了正向选择。与随机预期相比,由AUG-增益事件产生的58个预测的新ORF具有以下优势:长度更长、密码子适应指数(CAI)更高、Kozak评分更高、tRNA适应指数(tAI)更高。这 58 个推测的新 ORF 具有高表达性,很可能具有功能性,这为 58 个 AUG 增益突变的正选择提供了解释。我们的研究提出了 SARS-CoV-2 中新基因出现的可能机制。这一观点将有助于研究 SARS-CoV-2 的变异和进化。
Host-dependent C-to-U RNA editing in SARS-CoV-2 creates novel viral genes with optimized expressibility.
Rampant C-to-U RNA editing drives the mutation and evolution of SARS-CoV-2. While much attention has been paid to missense mutations, the C-to-U events leading to AUG and thus creating novel ORFs were uninvestigated. By utilizing the public time-course mutation data from the worldwide SARS-CoV-2 population, we systematically identified the "AUG-gain mutations" caused by C-to-U RNA editing. Synonymous mutations were of special focus. A total of 58 synonymous C-to-U sites are able to create out-of-frame AUG in coding sequence (CDS). These 58 synonymous sites showed significantly higher allele frequency (AF) and increasing rate (dAF/dt) than other C-to-U synonymous sites in the SARS-CoV-2 population, suggesting that these 58 AUG-gain events conferred additional benefits to the virus and are subjected to positive selection. The 58 predicted new ORFs created by AUG-gain events showed the following advantages compared to random expectation: they have longer lengths, higher codon adaptation index (CAI), higher Kozak scores, and higher tRNA adaptation index (tAI). The 58 putatively novel ORFs have high expressibility and are very likely to be functional, providing an explanation for the positive selection on the 58 AUG-gain mutations. Our study proposed a possible mechanism of the emergence of de novo genes in SARS-CoV-2. This idea should be helpful in studying the mutation and evolution of SARS-CoV-2.
期刊介绍:
Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.