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BRIEF RESEARCH REPORT article
Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Volume 14 - 2024 |
doi: 10.3389/fcimb.2024.1476605
Host-dependent C-to-U RNA editing in SARS-CoV-2 creates novel viral genes with optimized expressibility
Provisionally accepted- 1 Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
- 2 Qingdao Mental Health Center, Qingdao, Shandong Province, China
- 3 Qingdao Central Hospital, Qingdao, Shandong Province, China
- 4 Qingdao Haici Hospital, Qingdao, China
- 5 Qingdao Traditional Chinese Medicine Hospital, Qingdao, Shandong Province, China
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 world-wide SARS-CoV-2 population, we systematically identified the "AUG-gain mutations" caused by C-to-U RNA editing. Synonymous mutations were of special focus. Totally 58 synonymous C-to-U sites are able to create out-of-frame AUG in CDS. These 58 synonymous sites showed significantly higher allele frequency (AF) and increasing rate (dAF/dt) than other C-to-U synonymous sites in 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 CAI, higher Kozak scores, and higher 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.
Keywords: SARS-CoV-2, C-to-U RNA editing, novel genes, TAI, positive selection
Received: 06 Aug 2024; Accepted: 17 Sep 2024.
Copyright: © 2024 Zhang, Zhang, Li, Liu, Yu, Yang and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Wenli Zhang, Qingdao Mental Health Center, Qingdao, Shandong Province, China
Jiahuan Li, Qingdao Central Hospital, Qingdao, 266000, Shandong Province, China
Huiying Liu, Qingdao Haici Hospital, Qingdao, China
Yantong Yu, Qingdao Traditional Chinese Medicine Hospital, Qingdao, Shandong Province, China
Xiaoping Yang, Qingdao Haici Hospital, Qingdao, China
Wenqing Jiang, Qingdao Haici Hospital, Qingdao, China
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