PT  - JOURNAL ARTICLE
AU  - Li, Yan
AU  - Hou, Fanghua
AU  - Zhou, Meili
AU  - Yang, Xiaoping
AU  - Yin, Bin
AU  - Jiang, Wenqing
AU  - Xu, Huiqing
TI  - C-to-U RNA deamination is the driving force accelerating SARS-CoV-2 evolution
AID  - 10.26508/lsa.202201688
DP  - 2023 Jan 01
TA  - Life Science Alliance
PG  - e202201688
VI  - 6
IP  - 1
4099  - https://www.life-science-alliance.org/content/6/1/e202201688.short
4100  - https://www.life-science-alliance.org/content/6/1/e202201688.full
SO  - Life Sci. Alliance2023 Jan 01; 6
AB  - Understanding the molecular mechanism underlying the rampant mutation of SARS-CoV-2 would help us control the COVID-19 pandemic. The APOBEC-mediated C-to-U deamination is a major mutation type in the SARS-CoV-2 genome. However, it is unclear whether the novel mutation rate u is higher for C-to-U than for other mutation types, and what the detailed driving force is. By analyzing the time course SARS-CoV-2 global population data, we found that C-to-U has the highest novel mutation rate u among all mutation types and that this u is still increasing with time (du/dt > 0). Novel C-to-U events, rather than other mutation types, have a preference over particular genomic regions. A less local RNA structure is correlated with a high novel C-to-U mutation rate. A cascade model nicely explains the du/dt > 0 for C-to-U deamination. In SARS-CoV-2, the RNA structure serves as the molecular basis of the extremely high and continuously accelerating C-to-U deamination rate. This mechanism is the driving force of the mutation, adaptation, and evolution of SARS-CoV-2. Our findings help us understand the dynamic evolution of the virus mutation rate.