All throughout this pandemic, there have been headlines warning that “the virus is mutating to become more lethal.” A thread. (1/n)

We know that viruses do indeed mutate, but when are these mutations functionally meaningful and when do we get a different “strain” as opposed to just a different “isolate”? I will attempt to answer this question in this thread. (2/n)

Although coronaviruses do have a proofreading mechanism that corrects errors during replication, this mechanism is not perfect, so occasional mutations are acquired in the viral genome. The genome consists of RNA, which is then translated into protein. (3/n)

For translation to occur, the genome is scanned and read in triplets of RNA nucleotides. Each triplet codes for one amino acid (the building blocks of proteins). However, there are several triplets that can code for the same amino acid. (4/n)

For example, the triplets GCU, GCC, GCA, GCG all code for the amino acid alanine:
GCU = alanine
GCC = alanine
GCA = alanine
GCG = alanine
If a mutation occurs that changes that last nucleotide “U” in the triplet GCU to a “G”, you end up with GCG, which still codes for... (5/n)

...alanine, and does not result in a change in the protein:
GCU = alanine
GCG = still alanine
However, if the mutation changes the “C” at the second position of GCU to a “U”, you get GUU, which codes for a different amino acid, valine:
GCU = alanine
GUU = valine (6/n)

This will result in a change in the protein and may sound alarming, but in fact probably still won’t change the function of the protein. That’s because alanine and valine have very similar physical properties. (7/n)

However, if the mutation changes the “G” at the first position in the triplet to a “C”, you get CCU, which codes for the amino acid proline:
GCU = alanine
CCU = proline
Proline is known to change how a protein folds, which could affect the ultimate function of the protein. (8/n)

However, that may still not necessarily happen. It is actually quite difficult to predict exactly how an amino acid change will functionally affect a protein. Even if it does have an effect, this effect may only show in cell culture, but may not show in humans. (9/n)

Such is probably the case with the D614G amino acid change (where a D amino acid (aspartic acid) changed to a G amino acid (glycine)) that has been hyped in the news as making SARS-CoV-2 more transmissible. (10/n)

So far, this effect has only been shown in cell culture. And until an amino acid change has a clear effect on the properties of the virus (confers a different function in how the virus replicates or binds to host cells for example), we can’t call it a different strain. (11/n)

It is still the same strain, just a different isolate with a slight mutation in its genome that has no bearing on its function. (end)