Frequent homologous recombination limited to the Omicron BA.1 lineage among SARS-CoV-2 variants
DOI:
https://doi.org/10.51094/jxiv.1021Keywords:
COVID-19, Omicron variant, reverse mutation, homologous recombination, sequence exchangeAbstract
Since the emergence of SARS-CoV-2, variants carrying new mutations have played significant roles in global transmission. Among them, the Omicron variant, which surfaced in November 2021, stands out due to its unprecedented number of mutations, particularly in the spike protein. This paper investigates the anomaly of the BA.1 lineage of the Omicron variant, focusing on the presence of reverse mutations and potential homologous recombination. Using sequence data from GenBank, the study analyzes the mutation patterns of various Omicron subvariants and compares them with each other and with other major variants such as Alpha and Delta. The results reveal a notable peak of triple reverse mutations and relatively high frequencies in the emergence of quadruple or more reverse mutations in BA.1 lineage as traces of homologous recombination. The study also addresses the possibility of contamination by Delta variant sequences, ruling out this explanation based on the accompanying mutations. Given the unique recombination patterns observed only in the BA.1 lineage and the absence of such events in other variants, the study raises concerns about the potential lab origin of the Omicron BA.1 lineage, underscoring the need for rigorous oversight in facilities handling SARS-CoV-2.
Conflicts of Interest Disclosure
The author declares no conflict of interest exists.Downloads *Displays the aggregated results up to the previous day.
References
Korber, B., Fischer, W. M., Gnanakaran, S., et al. (2020). Tracking changes in SARS-CoV-2 spike: Evidence that D614G increases infectivity of the COVID-19 virus. Cell, 182(4), 812–827. https://doi.org/10.1016/j.cell.2020.06.043
Volz, E., Hill, V., McCrone, J. T., et al. (2021). Evaluating the effects of SARS-CoV-2 spike mutation D614G on transmissibility and pathogenicity. Cell, 184(1), 64–75. https://doi.org/10.1016/j.cell.2020.11.020
Hou, Y. J., Chiba, S., Halfmann, P., et al. (2020). SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. Science, 370(6523), 1464–1468.
https://doi.org/10.1126/science.abe8499
Miyata, T., & Yasunaga, T. (1986). Molecular evolution of mRNA: A method for estimating evolutionary rates of synonymous and amino acid substitutions from homologous nucleotide sequences and its application. Journal of Molecular Evolution, 16(1), 23–36.
https://doi.org/10.1007/BF01732067
Li, W. H., Wu, C. I., & Luo, C. C. (1985). A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Molecular Biology and Evolution, 2(2), 150–174.
https://doi.org/10.1093/oxfordjournals.molbev.a040343
Nikolaidis, M., Papakyriakou, A., Chlichlia, K., et al. (2022). Comparative analysis of SARS-CoV-2 variants of concern, including Omicron, highlights their common and distinctive amino acid substitution patterns, especially at the spike ORF. Viruses, 14(4), 707.
https://doi.org/10.3390/v14040707
Hassan, S. S., Kodakandla, V., Redwan, E. M., et al. (2022). Non-uniform aspects of the SARS-CoV-2 intraspecies evolution reopen question of its origin. International Journal of Biological Macromolecules, 222, 972–993.
https://doi.org/10.1016/j.ijbiomac.2022.09.184
Amicone, M., Borges, V., Alves, M. J., et al. (2022). Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution. Evolution, Medicine, and Public Health, 2022(1), 142–155. https://doi.org/10.1093/emph/eoac010
Kawasaki, Y., Abe, H., & Yasuda, J. (2023). Comparison of genome replication fidelity between SARS-CoV-2 and influenza A virus in cell culture. Scientific Reports, 13, 13105.
https://doi.org/10.1038/s41598-023-40463-4
Callaway, E. (2021). Heavily mutated Omicron variant puts scientists on alert. Nature, 600(7888), 21. https://doi.org/10.1038/d41586-021-03552-w
Jung, C., Kmiec, D., Koepke, L., et al. (2022). Omicron: What makes the latest SARS-CoV-2 variant of concern so concerning? Journal of Virology, 96(3), 02077–21.
https://doi.org/10.1128/jvi.02077-21
Mallapaty, C. (2022). The hunt for the origin of Omicron. Nature, 602(7897), 26–28. https://doi.org/10.1038/d41586-022-00215-2
Choi, B., Choudhary, M. C., Regan, J., et al. (2020). Persistence and evolution of SARS-CoV-2 in an immunocompromised host. The New England Journal of Medicine, 383(23), 2291–2293. https://doi.org/10.1056/NEJMc2031364
Kemp, S. A., Collier, D. A., Datier, R. P., et al. (2021). SARS-CoV-2 evolution during treatment of chronic infection. Nature, 592(7852), 277–282.
https://doi.org/10.1038/s41586-021-03291-y
Truong, T. T., Ryutov, A., Pandey, U., et al. (2021). Increased viral variants in children and young adults with impaired humoral immunity and persistent SARS-CoV-2 infection: A consecutive case series. EBioMedicine, 67, 103355.
https://doi.org/10.1016/j.ebiom.2021.103355
Wei, C., Shan, K. J., Wang, W., et al. (2021). Evidence for a mouse origin of the SARS-CoV-2 Omicron variant. Journal of Genetics and Genomics, 48(12), 1111–1121.
https://doi.org/10.1016/j.jgg.2021.12.003
Zhang, W., Shi, K., Geng, Q., et al. (2022). Structural basis for mouse receptor recognition by SARS-CoV-2 omicron variant. Proceedings of the National Academy of Sciences, 119(5), e2206509119. https://doi.org/10.1073/pnas.2206509119
Piplani, S., Singh, P. K., Winkler, D. A., et al. (2021). In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin. Scientific Reports, 11, 13063. https://doi.org/10.1038/s41598-021-92388-5
Kakeya, H., & Matsumoto, Y. (2022). A probabilistic approach to evaluate the likelihood of artificial genetic modification and its application to SARS-CoV-2 Omicron variant. ISPJ Transactions on Bioinformatics, 15, 22–29.
https://doi.org/10.2197/ipsjtbio.15.22
Kakeya, H., Arakawa, H., & Matsumoto, Y. (2023). Multiple probabilistic analyses suggest non-natural origin of SARS-CoV-2 Omicron variant. Zenodo.
https://doi.org/10.5281/zenodo.7470652
Kakeya, H., & Matsumoto, Y. (2023). Repeated emergence of probabilistically and chronologically anomalous mutations in SARS-CoV-2 during the COVID-19 pandemic. Zenodo. https://doi.org/10.5281/zenodo.8216232
Tanaka, A., & Miyazawa, T. (2023). Unnaturalness in the evolution process of the SARS-CoV-2 variants and the possibility of deliberate natural selection. Zenodo.
https://doi.org/10.5281/zenodo.8361577
Kakeya, H., & Kanazaki, T. (2023). Anomalous biases of reverse mutations in SARS-CoV-2 variants. Jxiv. https://doi.org/10.51094/jxiv.545
Kakeya, H. (2024). Anomalous US-wide prevalence of reversion mutants in the emergence of Omicron BA.1. Research Square.
https://doi.org/10.21203/rs.3.rs-4919461/v1
Kakeya, H. (2024). Anomalies in regional and chronological distributions of SARS-CoV-2 Omicron BA.1.1 lineage in the United States. medRxiv.
https://doi.org/10.1101/2024.08.14.24311991
Akaishi, T., Fujiwara, K., & Ishii, T. (2023). Genetic recombination sites away from the insertion/deletion hotspots in SARS-related coronaviruses. Tohoku Journal of Experimental Medicine, 259(1), 17–26.
Akaishi, T., Horii, A., & Ishii, T. (2022). Sequence exchange involving dozens of consecutive bases with external origin in SARS-related coronaviruses. Journal of Virology, 96(15), 1–4. https://doi.org/10.1128/jvi.01002-22
Martin, D. P., Lytras, S., Lucaci, A. G., et al. (2022). Selection analysis identifies clusters of unusual mutational changes in Omicron lineage BA.1 that likely impact spike function. Molecular Biology and Evolution, 39(6), msac061.
https://doi.org/10.1093/molbev/msac061
Gordon, M. R. and Strobel, W. P. (2024) Behind Closed Doors: The Spy-World Scientists Who Argued Covid Was a Lab Leak. Wall Street Journal.
https://www.wsj.com/politics/national-security/fbi-covid-19-pandemic-lab-leak-theory-dfbd8a51
Butler, D. (2011). Fears grow over lab-bred flu. Nature, 480(7378), 421–422. https://doi.org/10.1038/480421a
- (2014). Biosafety in the balance. Nature, 510(7506), 443.
https://doi.org/10.1038/510443a
Silver, A. (2022). Taiwan’s science academy fined for biosafety lapses after lab worker contracts COVID-19. Science.
https://doi.org/10.1126/science.ada0525
Arakawa, H. (2024). The natural evolution of RNA viruses provides important clues about the origin of SARS-CoV-2 variants. SynBio, 2(3), 285–297.
Downloads
Posted
Submitted: 2025-01-03 04:33:44 UTC
Published: 2025-01-09 01:04:45 UTC
License
Copyright (c) 2025
Hideki Kakeya
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.