The mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitness
Abstract Although vaccines and treatments have strengthened our ability to combat the COVID-19 pandemic, new variants of SARS-CoV-2 continue to emerge in human populations. Because the evolution of SARS-CoV-2 is driven by mutation, a better understanding of its mutation rate and spectrum could impro...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61555-x |
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| author | Jori Symons Claire Chung Bert M. Verheijen Sarah J. Shemtov Dorien de Jong Gimano Amatngalim Monique Nijhuis Marc Vermulst Jean-Francois Gout |
| author_facet | Jori Symons Claire Chung Bert M. Verheijen Sarah J. Shemtov Dorien de Jong Gimano Amatngalim Monique Nijhuis Marc Vermulst Jean-Francois Gout |
| author_sort | Jori Symons |
| collection | DOAJ |
| description | Abstract Although vaccines and treatments have strengthened our ability to combat the COVID-19 pandemic, new variants of SARS-CoV-2 continue to emerge in human populations. Because the evolution of SARS-CoV-2 is driven by mutation, a better understanding of its mutation rate and spectrum could improve our ability to forecast the trajectory of the pandemic. Here, we use circular RNA consensus sequencing (CirSeq) to determine the mutation rate of six SARS-CoV-2 variants and perform a short-term evolution experiment to determine the impact of these mutations on viral fitness. Our analyses indicate that the SARS-CoV-2 genome mutates at a rate of ∼1.5 × 10−6/base per viral passage and that the spectrum is dominated by C → U transitions. Moreover, we find that the mutation rate is significantly reduced in regions that form base-pairing interactions and that mutations that affect these secondary structures are especially harmful to viral fitness. In this work, we show that the biased mutation spectrum of SARS-CoV-2 is likely a result of frequent cytidine deamination and that the secondary structure of the virus plays an important role in this process, providing new insight into the parameters that guide viral evolution and highlighting fundamental weaknesses of the virus that may be exploited for therapeutic purposes. |
| format | Article |
| id | doaj-art-2d0508becc4f46789993dd0106cfe044 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-2d0508becc4f46789993dd0106cfe0442025-08-20T04:03:01ZengNature PortfolioNature Communications2041-17232025-07-0116111310.1038/s41467-025-61555-xThe mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitnessJori Symons0Claire Chung1Bert M. Verheijen2Sarah J. Shemtov3Dorien de Jong4Gimano Amatngalim5Monique Nijhuis6Marc Vermulst7Jean-Francois Gout8Translational Virology, Department of Medical Microbiology, University Medical CenterLeonard Davis School of Gerontology, University of Southern CaliforniaLeonard Davis School of Gerontology, University of Southern CaliforniaLeonard Davis School of Gerontology, University of Southern CaliforniaTranslational Virology, Department of Medical Microbiology, University Medical CenterDivision Child Lung Diseases, Regenerative Medicine Center Utrecht, University Medical CenterTranslational Virology, Department of Medical Microbiology, University Medical CenterLeonard Davis School of Gerontology, University of Southern CaliforniaDepartment of Biological Sciences, Mississippi State UniversityAbstract Although vaccines and treatments have strengthened our ability to combat the COVID-19 pandemic, new variants of SARS-CoV-2 continue to emerge in human populations. Because the evolution of SARS-CoV-2 is driven by mutation, a better understanding of its mutation rate and spectrum could improve our ability to forecast the trajectory of the pandemic. Here, we use circular RNA consensus sequencing (CirSeq) to determine the mutation rate of six SARS-CoV-2 variants and perform a short-term evolution experiment to determine the impact of these mutations on viral fitness. Our analyses indicate that the SARS-CoV-2 genome mutates at a rate of ∼1.5 × 10−6/base per viral passage and that the spectrum is dominated by C → U transitions. Moreover, we find that the mutation rate is significantly reduced in regions that form base-pairing interactions and that mutations that affect these secondary structures are especially harmful to viral fitness. In this work, we show that the biased mutation spectrum of SARS-CoV-2 is likely a result of frequent cytidine deamination and that the secondary structure of the virus plays an important role in this process, providing new insight into the parameters that guide viral evolution and highlighting fundamental weaknesses of the virus that may be exploited for therapeutic purposes.https://doi.org/10.1038/s41467-025-61555-x |
| spellingShingle | Jori Symons Claire Chung Bert M. Verheijen Sarah J. Shemtov Dorien de Jong Gimano Amatngalim Monique Nijhuis Marc Vermulst Jean-Francois Gout The mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitness Nature Communications |
| title | The mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitness |
| title_full | The mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitness |
| title_fullStr | The mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitness |
| title_full_unstemmed | The mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitness |
| title_short | The mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitness |
| title_sort | mutational landscape of sars cov 2 provides new insight into viral evolution and fitness |
| url | https://doi.org/10.1038/s41467-025-61555-x |
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