Mutations in SARS-CoV-2: friend or foe?
Researchers are using mutations in the SARS-CoV-2 genome to study how the disease is spreading – but what are mutations and what do they mean for the future of the pandemic?
All living things use molecules called nucleic acids to store the instructions they need to make the components of their bodies. In humans (and most other organisms) that's DNA - deoxyribonucleic acid. But some viruses, including SARS-CoV-2, use a related molecule called RNA - ribonucleic acid. The full DNA or RNA instructions contained in a living thing are called its "genome".
Both DNA and RNA consist of long chains of four small molecules called nucleotides. These are the genetic letters that spell out the messages contained in the code. The order of the individual nucleotides is called the “sequence” of a genome, and this determines the repertoire of proteins an organism makes. In viruses, like SARS-CoV-2, some of these proteins form the physical "body" of the virus, while others perform tasks such as copying (replicating) the RNA to make new virus particles.
Changes to the nucleotide sequence are called “mutations”. These can be likened to genetic spelling mistakes where one nucleotide is accidentally switched for another, or strings of nucleotides can be inserted into or deleted from the genome, changing the genetic instructions. Mutations like these arise through random errors during genome replication, or sometimes exposure to chemicals or ionising radiation, which can damage nucleic acids.
Often, and contrary to what you might expect, mutations will frequently have little or no effect on an organism, including the SARS-CoV-2 coronavirus. This is because some parts of the genome do not code directly for proteins but instead have structural or regulatory roles that are less critical to the functioning of the organism. Also, owing to the way the genetic code works, a number of different combinations of genetic letters can code for the same protein. This means some mutations are said to be "silent". Other mutations, though, can have a dramatic effect. They might stop a certain protein from working and thus prevent the virus from replicating or spreading.
On the other hand, some mutations can change the function of a protein in a way that benefits the virus. If a beneficial mutation improves how the virus replicates or spreads, then the mutation may become more common over time as it gets passed on to new copies of the virus. In some viruses, these mutations can present a problem for human health. For example, mutations in one of the proteins that the H5N1 ‘bird flu’ virus uses to infect birds allowed the virus to gain the ability to infect humans too1. Another issue is that a high mutation rate can turn the virus into a ‘moving target’ for both the human immune system and drug or vaccine development, which rely on targeting specific virus proteins. This is why we need a new vaccine for seasonal influenza every year, and why HIV has so far proved elusive as a vaccine target.
Mutations can also be used to construct an evolutionary tree of the virus, similar in principle to those made by Charles Darwin to describe how species evolve over time. Differences in the genome of virus samples from different people can be used to see how closely related different samples are, and this can reveal when and where the virus is being transmitted between people. This method can be used for a variety of different disease-causing microbes, and in the past has been used to trace outbreaks of the bacterial superbug MRSA in hospitals4. Insights from this kind of work can inform public health policy-making, and help us to understand more about the spread of the virus.
So what does this mean for SARS-CoV-2? One reason to be optimistic is that the mutation rate in this virus is much lower than for seasonal influenza (around 4-fold lower according to one analysis2,3). It is possible that this could reduce the chance of the virus mutating to a more deadly or more transmissible form, and makes vaccine and drug development more straightforward. There is no evidence so far that any of the mutations occurring are producing strains of the virus with differences in symptoms or transmissibility.
Currently, the mutations scientists are seeing in SARS-CoV-2 are not a cause for concern and they do not seem to be causing meaningful changes in the biology of the virus or the disease it causes. However, mutations are being used as a useful tool to track the spread of the pandemic. It is important to remember that this may change as the pandemic progresses, especially as more people are infected and if either natural or vaccine-mediated immunity comes into play, so scientists are keeping a close eye on the evolution of the virus as it continues to spread.