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What is a mutation for the SARS-CoV-2 coronavirus?

Text updated on 2021-01-14


Viruses mutate all the time. Mutations in the SARS-CoV-2 coronavirus that affect the Spike protein, which is the key to the virus' entry into human cells and is also the target of vaccines, are particularly monitored by scientists.

SARS-CoV-2 is a coronavirus with RNA (ribonucleic acid): the support of its genetic material is an RNA strand (see the question What do the abbreviations COVID, SARS, CoV, RNA, etc. mean?). RNA is a linear molecule made up of a sequence of letters (A, U, G or C) called ribonucleotides. The genome of SARS-CoV-2, the entire genetic material of the virus, is a sequence of nearly 30,000 letters, making it a "long" genome for a virus. It was first published on January 11, 2020. 

The coronavirus lives and reproduces in human cells. To reproduce itself, it copies its genome within the cell it has infected, which involves copying every letter of its RNA strand. New virus particles will be formed in the infected cell, containing these RNA copies, and will enter other cells and infect them in turn. Entry into the cell is done with the help of the coronavirus Spike protein which binds to certain receptors in the cell, called ACE2, on which the Spike protein works like a key to open a door.

When copying the coronavirus genome, mistakes are sometimes made: one letter can be replaced by another (substitution), added (insertion) or deleted (deletion). These are called mutations and they appear randomly. We don't know when or where they will appear in the RNA molecule, or what error will be created. This is a normal phenomenon that can be observed in all viruses. SARS-CoV-2 has a correction system for its errors and therefore there are globally fewer mutations than for other viruses that do not have a correction system. To date, several thousand mutations have been identified. In the majority of cases, the mutation does not change the properties of the virus. This is known as a silent mutation. In other cases, it can cause changes in the proteins of the coronavirus. These proteins determine the transmission capacity, the speed of replication, and the ability to bypass the coronavirus' immune defences. Changes in the proteins can therefore sometimes have an impact on the reproduction rate of SARS-CoV-2 (see question Lethality, mortality, excess mortality, R0, kappa: what are we talking about?).

The Spike protein plays a major role in the transmissibility of the virus and in the vaccination strategy. Indeed, the vaccines developed are based on the recognition of this Spike protein by the immune system. Consequently, mutations affecting this protein are closely monitored by scientists. As of December 15, 2020, researchers analysing British coronaviruses had identified 1,777 different mutations that modify the Spike protein.

Mutations appear all the time. Some disappear right after they appear when the mutated virus doesn't infect anyone. Other mutations will persist over time and will spread to another part of the population. By comparing coronavirus sequences from patients at different times and in different parts of the world, we can find viruses that are very similar to each other and reconstruct the sequence of mutations that have appeared one after the other in a series of people who have become infected one after another. In this way, we can reconstruct a tree of mutations. In each branch of the tree, it has been measured that, for SARS-CoV-2, about two mutations appear each month. When the coronavirus is circulating in the human population and infecting several million humans, it becomes increasingly likely that the same mutation (the same change in the RNA sequence of the virus) will appear independently in two individuals.


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Sources

Continuously updated site that lists all the genomes of SARS-CoV-2.

A catalog of mutations of of the SARS-CoV-2 coronavirus (COVID-19)

The first genome of SARS-CoV-2 was published on January 11, 2020 by Chinese virologist Yongzhen Zhang following a phone call with his Australian collaborator.

Cyranoski, D., Dolgin, E., Gaind, N., Hall, S., Ledford, H., Lewis, D., ... & Subbaraman, N. (2020). Nature's 10: ten people who helped shape science in 2020. Nature, 563-576.

Genome evolution analysis of SARS-CoV-2 which suggests that mutations are accumulating at a rate of 1 or 2 mutations per month and that the coronavirus emerged in October - November 2019.

Duchene, S., Featherstone, L., Haritopoulou-Sinanidou, M., Rambaut, A., Lemey, P., & Baele, G. (2020). Temporal signal and the phylodynamic threshold of SARS-CoV-2. Virus Evolution, Volume 6, Issue 2, July 2020, veaa061, https://doi.org/10.1093/ve/veaa061

The target of the vaccine developed by Pfizer BioNtech is the entire Spike protein.

Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., ... & Gruber, W. C. (2020). Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccinia. New England Journal of Medicine.

The target of the vaccine developed by Astra Zeneca / Oxford University team is the Spike protein.

Voysey, M., Clemens, S. A. C., Madhi, S. A., Weckx, L. Y., Folegatti, P. M., Aley, P. K., ... & Bijker, E. (2020). Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet.

The target of the vaccine developed by ModeRNA is the Spike protein.

Jackson, L. A., Anderson, E. J., Rouphael, N. G., Roberts, P. C., Makhene, M., Coler, R. N., ... & Beigel, J. H. (2020). An mRNA vaccine against SARS-CoV-2-preliminary report. New England Journal of Medicine.

The analysis of 126,219 genomes from patient samples collected by the British consortium COG-UK up to December 15, 2020 identified 1,777 different mutations modifying the Spike protein.

Genomics UK Consortium. COG-UK update on SARS-CoV-2 Spike mutations of special interest. 2020. Last accessed 12 January 2021.

Further reading

What is a variant of the SARS-CoV-2 coronavirus?

How does a variant of the SARS-CoV-2 coronavirus spread?

Which variants of the SARS-CoV-2 coronavirus have attracted attention?

What do we know about the British variant?

Do the variants call into question the efficacy of the vaccines?