Some of the latest nonsense from anti-vaxxers is that “viruses don’t mutate” or “the COVID virus does not mutate in the unvaccinated.” They use this unscientific garbage to justify their own lack of vaccination or why the vaccine is useless.
Of course, most of us understand that those two statements are fundamentally wrong. I partially discussed this in a previous post that attempted to refute a common anti-vaxxer claim that viruses become less virulent over time. That claim wasn’t even close to the truth.
So let’s take a close look at these nonsensical claims from our anti-vaccine friends that the SARS-CoV-2 virus that causes COVID-19 does or does not mutate. (Note — for simplicity, I’m going to call it the COVID-19 virus just because fewer people are familiar with the term, SARS-CoV-2.)
All viruses mutate
However, depending on the type of virus, some mutate faster than others. DNA viruses, such as smallpox, mutate at a much lower rate than RNA viruses, such as HIV, influenza virus, and, yes, the COVID-19 virus, SARS-CoV-2.
Time for a little biology. The genetic code tells cells what proteins to produce (and proteins are the building blocks of life). It is made up of just four bases — adenosine, tyrosine, guanine, and cytosine, abbreviated as A, T, G, and C. DNA, which is a double helix, always pairs A with T and G with C.
Normally, during the process called transcription, RNA polymerase makes a copy of a gene from one strand of the double-stranded DNA to mRNA whenever required by the cell. In other words, the mRNA sequences in the cell usually correspond directly to the DNA sequences in our genes.
These mRNA sequences “carry” that genetic message to a ribosome for translation, where tRNA triplets (three bases), which code for one amino acid, attach to the appropriate mRNA triplet, adding one amino acid to the protein chain.
As in DNA, genetic information in mRNA is contained in the sequence of nucleotides, which are arranged into codons consisting of three ribonucleotides each. Each codon codes for a specific amino acid, except the stop codons, which terminate protein synthesis. (Just to confuse this, RNA uses uracil, U, instead of guanine, so U pairs with A in RNA.)
At this point, note that the mRNA does nothing to the DNA strand in your genes – it merely reads the DNA sequence that represents the gene. I cannot stress this enough – mRNA does nothing to the DNA, it just reads it passively.
Yes, that’s a lot of cell biology, but I’m just scratching the surface because I don’t want any of you to fall asleep. If you want to take a deep dive into the science of mRNA and mRNA vaccines, my friend Edward Nirenberg wrote two articles that will satisfy your desires – he makes it clear how this all works and doesn’t work.
Alan McHughen, in his outstanding book, “DNA Demystified: Unraveling the Double Helix,” describes how mRNA works:
When an mRNA strand exits the nucleus and enters the cytoplasm, it attaches to ribosomes, and this is where protein synthesis progresses. The ribosome reads the base sequence of the mRNA, three bases at a time. Each three-base triplet, called a codon, specifies a particular amino acid, except for a few with regulatory functions (e.g., UGA =“Stop!”).
If the first three-base codon is AUG, then a molecule of the amino acid methionine is brought into place. If the next triplet is AAA, that brings in the amino acid lysine. The methionine and lysine molecules are attached together. The next triplet is, say, GCC, and that brings in alanine, which is attached to the lysine. The ribosome has read nine bases, AUGAAAGCC, and compiled a short chain of three amino acids, abbreviated Met-Lys-Ala, or MKA (see amino acid abbreviations here).
The ribosome continues reading all of the mRNA bases until it hits a stop signal—which is also a triplet codon such as UGA—and the now long chain of amino acids falls loose. This chain may be a functional protein immediately, or, more usually, it might undergo some additional post-translational processing by enzymes to become active.
Mutations happen
Because no DNA copying process is perfect, errors appear which give rise to mutations. The pairing of bases is extremely accurate, but it’s not perfectly accurate. That’s why most cancers are caused by random mutations since DNA replication can be 99.999% accurate but that leaves the possibility of millions or billions of mutations over a lifetime of a person.
Most mutations are harmless. Some are harmful. That’s why early organisms evolved with a system of “proofreading” the DNA to excise errors. Over the 3.5 billion years of life on earth, the proofreading system became better and better, though still not perfect.
The aforementioned DNA viruses have very good error correction mechanisms, which means they have a low mutation rate. For example, smallpox has an error rate of about one in a billion base pairs. RNA viruses usually (and we’ll discuss the one exception) lack such a proofreading mechanism, so the error rate, or mutation rate, in their RNA is much much higher, such as we see in the COVID-19 virus.
But something that anti-vaxxers, and many others, miss is that not all mutations are neutral or harmful. Some are actually useful.
As I mentioned before, there is a huge overlap in the Venn diagram of vaccine and evolution deniers. They seem to lack basic education in biology, especially evolution, which is germane to this discussion.
Evolution is rather simple. It is the change in heritable characteristics of a population of organisms over time as a result of natural selection or genetic drift. Essentially, random mutations confer some characteristics to an organism that makes it either more fit (able to produce offspring and thus transfer its genes to the next generation) or less fit (it either dies before reproducing or makes it less able to reproduce). There are actually some mutations that provide no immediate benefit to the organism but could subsequently do so in response to a change in their environmental niche.
Evolution is random. There is no plan. There is no overarching reason for evolution. And evolution certainly couldn’t care less about humans one way or another. Evolution benefits no one except the organisms and how they reproduce in a particular environmental niche.
Just to be clear, the fact of evolution is observed in fossils and living organisms. Natural selection is observed in populations of organisms. Genetic drift is also observed. These are facts only dismissed by evolution deniers. The theory of evolution just describes the mechanisms of evolution. Despite the irrational claims of creationists, there has never been anything presented by them that scientifically dismisses the fact and theory of evolution. Nothing.
The scientific evidence supporting the fact and theory of evolution is literally a mountain. There are well over a million papers written about evolution, even though all scientific theories are provisional, meaning they could be dropped if there were a similar quantity and quality of papers disputing evolution, we might rethink it. But there isn’t.
Back to mutations Beneficial mutations will be positively selected by natural selection and will predominate over members of their species that lack that mutation. For example, SARS-CoV-2 variants like Delta and Omicron can infect other hosts easier and faster, and they can overcome our immune defenses faster. They become the predominant mutations very quickly.
RNA viruses, like the COVID-19 virus, mutate a lot
Like I mentioned above, RNA viruses lack the proofreading system that DNA viruses have, so their mutations rate generally varies from one in a thousand to one in a million bases.
This rate of mutation is complex. There’s an evolutionary balance between enough mutation to make exciting new variants, and excessive mutation. In fact, molnupiravir, one of the newer drugs that may be useful against SARS-CoV-2, does exactly this. It causes the COVID virus to mutate so much, it can’t make faithful copies of itself, and dies out in the body. However, it could cause the COVID virus to mutate into a more dangerous form, but the risk is very small.
The COVID-19 virus is kind of a unique RNA virus which makes it dangerous.
DNA viruses are much larger than RNA viruses. For example, the smallpox virus has 186,000 bases (written as 186 kilobases, or kb). RNA viruses are generally much smaller:
- poliovirus : 7.4 kb
- rhinovirus-14 : 7.1 kb (one of many cold viruses)
- influenza A virus : 13.6 kb (‘flu)
- human immunodeficiency virus : 9.2 kb (HIV/AIDS)
SARS-CoV-2 is approximately 30 kb, making it one of the largest RNA viruses known, although it’s still substantially smaller than DNA viruses. The problem with larger RNA viruses is that, because they lack a correction mechanism, they have a greater risk of harmful mutations.
Coronaviruses, on the other hand, are unique among RNA viruses in that they have a built-in proofreading mechanism. This gives them two huge advantages over other RNA viruses and, frankly, over DNA viruses.
- Because they’re larger, they can have more peptides to confuse and overcome the host’s immune response. Even a few extra peptides can confer a huge evolutionary advantage — because there are quadrillions more variations that the virus can evolve into that can confuse our immune system.
- With controlled mutation, they can adapt quickly. This is what we’re seeing.
Scientists have known about coronavirus proofreading for years — we’ve seen the consequences in familiar coronaviruses, which re-infect people again and again, mainly causing colds. But now we’re seeing the advantage with the COVID-19 virus which can mutate frequently.
Why does the COVID-19 virus mutate so much?
The reasons why we observe so much more mutation with SARS-CoV-2 than other viruses is because:
- It evolved with an excellent balance between size and mutation rate
- It’s a new virus to humans and is unfamiliar to our immune system
- Viruses can only mutate when it can reproduce in unvaccinated individuals.
We could blame the vaccine deniers, and they share a part of the responsibility for this by allowing the virus to spread and mutate. However, a lot of blame can be placed on governments that haven’t put enough consistent effort into stopping this pandemic. Of course, there seems to be a total lack of effort into increasing the vaccination rate in less-developed countries.
Despite how well the COVID-19 virus avoids the immune system, vaccines still work, because they induce a broad immune memory of the key antigens on the virus, better than what could be expected from a natural infection, which happens to increase your risk of death.
Vaccines give you the best protection against the virus, although it’s going to be an ongoing war with this very sneaky virus.
Citations
- Domingo E, García-Crespo C, Lobo-Vega R, Perales C. Mutation Rates, Mutation Frequencies, and Proofreading-Repair Activities in RNA Virus Genetics. Viruses. 2021 Sep 21;13(9):1882. doi: 10.3390/v13091882. PMID: 34578463; PMCID: PMC8473064.
- Duffy S. Why are RNA virus mutation rates so damn high? PLoS Biol. 2018 Aug 13;16(8):e3000003. doi: 10.1371/journal.pbio.3000003. PMID: 30102691; PMCID: PMC6107253.
- Moss B. Poxvirus DNA replication. Cold Spring Harb Perspect Biol. 2013 Sep 1;5(9):a010199. doi: 10.1101/cshperspect.a010199. PMID: 23838441; PMCID: PMC3753712.
- Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R. Viral mutation rates. J Virol. 2010 Oct;84(19):9733-48. doi: 10.1128/JVI.00694-10. Epub 2010 Jul 21. PMID: 20660197; PMCID: PMC2937809.
