Authors: Wenqing Jiang (Qingdao Haici Hospital, China)
Take a peek behind the scenes of a recent article published by Future Virology, titled ‘Pros and cons of the application of evolutionary theories to the evolution of SARS-CoV-2,’ as Wenqing Jiang (Qingdao Haici Hospital, China) discusses the rationale behind establishing and applying novel evolutionary theories for the study of RNA viruses.
What inspired you to write this piece?
As medical workers dealing with patients with respiratory diseases, we feel obligated to contribute to fighting against COVID-19. We saw numerous papers reporting the origin and evolution of SARS-CoV-2. While acknowledging that understanding the virus evolution may not directly contribute to the prevention or cure of COVID-19, we were concerned that many bioinformatics labs simply mechanically applied the evolutionary formula to the virus sequences. We are worried about the authenticity of their methodologies, and we sincerely appeal that, before we apply any evolutionary theories, we must first understand some basic knowledge of the organism.
What are the benefits of applying evolutionary theories when researching the origin of pathogens?
Currently, the traditional theories, algorithms, and formula are the only way to solve the origin and evolution of coronaviruses. Before any new theories are established, these classic theories are the best – sequence similarities are still the best reflection of phylogeny.
Why might these classic theories and formula not be appropriate when applied to SARS-CoV-2?
The mutation rate for classic DNA organisms is contributed by the DNA replication error, which is approximately 1e-8. But for RNA viruses (SARS-CoV-2), their mutation rate is caused by both RNA replication error and the host’s RNA modifications (C–U and A–I). The RNA modification rate is several orders of magnitude higher than replication error rates.
How do you think the study of the evolution and origin of SARS-CoV-2 could be improved?
Technically, when calculating dN, dS (nonsynonymous and synonymous substitution rates, representing the divergence), or any other linkage analyses, the C-T and A-G mismatches should be excluded. This is because a basic assumption of evolution is the constant mutation rate caused by replication errors, but for RNA viruses the C-T and A-G mismatches are possibly in part due to the C-U and A-I modifications. Other mismatch types could only be caused by replication error as no such RNA modification types are known. We are not sure whether this amendment makes sense, but it is worth trying.
What are your predictions for the next 10–15 years in this field? What do you hope to see?
We predict that the field of virus evolution could incorporate more novel evolutionary theories. We hope to see the many new theories applied individually to distinguish the DNA organisms from RNA organisms, taking into account their distinct features of nucleotide components, mutation rates, and reproductive patterns.
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