I want to talk about the principle of mutation, mainly because I feel like it’s going to come up a lot and it’s best to clear the air.
The first things to discuss are DNA and RNA.
DNA is actually an acronym that stands for deoxyribonucleic acid, which is a bit of a mouthful. What you really need to know is that DNA is the code for all living things. DNA is double stranded- which means that it looks a bit like a ladder- and it’s a helix, which means that it looks like a ladder that’s been grabbed at both ends and twisted:
DNA looks like the photo above. It’s got a backbone, which is like the outer parts of the ladder, and several bases (adenine, thymine, cytosine and guanine) which make up the rungs. The order of the bases in DNA act like instructions to make important things for the cell, virus or bacteria that owns the DNA.
RNA is also a type of genetic coding molecule, but it has a slightly different structure. RNA stands for ribonucleic acid, so the first difference between it and DNA is that where DNA uses deoxyribose, RNA only uses ribose. The other main difference between RNA and DNA is that while DNA looks like a ladder and is double stranded, RNA usually only single stranded (it looks like a ladder that’s been chopped vertically in half). That being said, there are notable exceptions to this- some viruses use double stranded RNA for their genome.
For more information on DNA and RNA, check out this link!
A mutation is a change in the genetic code- either DNA or RNA- that happens when that genetic code is duplicated. It’s like a game of telephone- if you whisper in someone’s ear, “I hear there’s a party tonight” and they tell the next person, “I hear bears at the party.” there’s been a mutation. Actually, there’s been two mutations- there’s got changed to bears and the word tonight went missing entirely!
A genetic code is just like a sentence in a game of telephone. The genome of any living thing is made up of a sequence of bases, which are like the alphabet that makes up the words in a sentence. Just like a particular series of letters in a sentence, for example “C-A-T,” makes a particular word (in this case, ‘cat’), a particular series of bases in a genome code for a particular amino acid. When a bunch of amino acids are put next to each other, you get a protein. Just like a sentence (‘the cat in the hat’) has a particular meaning based on the words in the sentence and the order they show up in, a protein will have a specific function based on the amino acids in it and the orders they show up in. So in our sentence analogy:
- Bases = letters
- Amino acids = words
- Proteins = sentence
When a cell divides or a virus makes more copies of itself, they have to copy their genome. When a genome is copied those bases are usually copied correctly. But sometimes there’s a mistake. Just like there’s became bears by changing just one letter, a genetic code can be changed a lot by one miscopied base. This type of a mutation, one that changes one ‘word’ for another, is called a missense mutation. In a cell or in a virus, it leads to one amino acid in a protein being swapped out for a different amino acid. Just like changing there’s to bears completely changes the function of the sentence (from a fun invitation to a worrying observation), a missense mutation often changes the way that a protein works.
Now let’s look at the second ‘mutation’ in our game of telephone. When you whispered your sentence to the person next to you, they accidentally ended the sentence after the word ‘party’ and forgot the word ‘tonight!’ This type of mutation, one that causes the sentence to end early, is called a nonsense mutation. In a cell or a virus, it leads to a protein being cut off too early. You end up with a protein that’s much shorter than it should be and a lot of the time that protein doesn’t work anymore.
Mutations happen all the time. The reason why humans aren’t walking around completely mutated beyond belief is because our cells are smart- really smart- and they have ways of catching and fixing mistakes that happen in DNA replication. Mistakes are caught and repaired by a whole cast of proteins but we’re just going to call the whole process the cell’s proofreading mechanism. But the proofreading mechanism is only useful in DNA replication. When a DNA-using virus infects a cell, it forces the cell’s own gene copying machines to make more of the virus’ genetic materials and, eventually, more viruses. If you have a virus like smallpox, which uses DNA to carry its genes, then the host cell’s proofreading mechanism can catch any mistakes when the viral DNA is being made and repair it. But if you have a virus like Ebola that uses RNA?
RNA viruses bring their own replication machines to the party, and don’t use the host cell’s smarter, more careful machines. Because of this, RNA viruses tend to mutate very, very quickly. Every time a virus replicates, or copies itself, that’s a chance for it to mutate. And a virus copies itself thousands and thousands of times in every single host. That’s a lot of chances for mutation, and a lot of chances for the virus to change how it behaves very quickly.
Coronaviruses like SARS-CoV-2 (also called the novel coronavirus) are interesting, because their RNA replication machines actually do proofread. So how do the mutations happen? It’s possible that when the virus is trying to replicate in a new location- say, a species it hasn’t infected before- the selection pressure (the new environment forcing the virus to find a new way to do things) of the environment causes it to dial down the sensitivity of that proofreading mechanism. In other words, the virus will ‘purposefully’ (in quotes, because viruses aren’t alive so really it isn’t purposeful so much as the mechanism of evolution) begin to make more mistakes, in the hopes that it’ll hit upon a mutation that will help it survive in this new species.
(Think of a student working on a paper at 2 am the day before it’s due, banging their head against a keyboard hoping some of that jumble will turn into something usable. That sort of a deal).
Coronaviruses are also known to do something called homologous recombination. They can take pieces of the genome from another virus and incorporate it into their own. Sometimes this can help the virus survive a new host or environment.
(Now imagine this same student giving up and copy/pasting an entire webpage into their essay. This is not recommended).
(For more information on specific ways viruses mutate, check out this link.)
Now, just because a virus can mutate quickly doesn’t mean that it’s suddenly going to develop an insane battery of symptoms (this virus isn’t playing Plague Inc.). A lot of the time, the mutations are actually bad for the virus. Most of the time, the mutations are neither good nor bad. And all of the time mutations make it easier for virologists and epidemiologists to understand how the virus works, where it came from, and how to fight it.
For more information on viral mutation and why it isn’t the start of the apocalypse, I suggest this lovely letter in Nature Microbiology. It really is very good.
References:
- Sanjuán, R., Domingo-Calap, P. Mechanisms of viral mutation. Cell. Mol. Life Sci. 73, 4433–4448 (2016). https://doi.org/10.1007/s00018-016-2299-6
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Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission
- DNA and RNA: Computational Medicine Center at Thomas Jefferson University. (n.d.). Retrieved from https://cm.jefferson.edu/learn/dna-and-rna/
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