Note that here we're not talking about a single mutation but 17 non-synonymous (they change the protein) mutations with 3-4 with known effects on the interactions of the resulting proteins
What are you talking about? Sequence is unstable due to size? Coronavirus has proofreading mechanism that corrects most mutations due to errors, the estimate for mutation speed before this variant emerged was 2 mutations per month so this variant has ~10 months of evolution in them but probably evolved much faster for some reason. This is very much a surprise
The error rate is in terms of the number of nucleotides addended to the polymerizing RNA during replication
the mutation rate is primarily a result of RNA replication, _not_ time. this means more replication events leads to more "errors", this also means longer sequence has a higher rate of error than a shorter sequence. at a length of ~29k bp the coronavirus sequence is very error prone, so error prone that this is approaching the upper limit of stability.
it seems you are mistaking DNA proofreading for an RNA proofreading mechanism, which happens to be negative selection upon nonfunctional mutant/variant. there is no recognized enzymatic [rdRNApol] error correction associated with the coronavirus.
"the RNA polymerases of RNA viruses are the kings of errors – these enzymes screw up as often as one time for every 1,000 – 100,000 nucleotides polymerized. This high rate of mutation comes from the lack of proofreading ability in RNA polymerases. These enzymes make mistakes, but they can’t correct them. Therefore the mutations remain in the newly synthesized RNA." [0]
none of these error prone generated mutations are surprising, they are to be expected espescially when the virus is given opportunity to replicate at a high cyle rate.
this is very much not a surprise, if you are aware of the properties of +ssRNA virus.
you dont seem to understand either concept. mutation is passed from individuals by vertical or horizontal transmission. variation of a gene [alleles] are mutations, mutations are the index variation. mutation is a change in the gene sequence, this is variation, this has created a mutant, also known as a variant.
mutation is also a term loaded with connotations due to popular depictions.
sexual reproduction is the mechanism of verticall transmission of variation of genetic sequence through a population.
genetic drift is also a mechanism of variation of a population.
the long and short of it is that mutation and variation, are tied together, they are the same thing.
you also seem to have overlooked the abuse of the term mutation, by the original article title, the use of mutation is slicker, than the use of error prone generated variant.
the use of the term strain is also erroneous in this context.
Not horrible or shocking, but concerning. Mutation is expected but the more strains there are the more likely one turns out to be unaffected by the vaccine and we find ourselves back at square one.
there is considerable selective pressure upon the spike protien, very large changes to this protien are not frequently viable, as the virus would need to find a new trophic target or a new host altogether.
We are tracking these changes closely and concommitantly can change the sequence of mRNA, responsively, and pre-emptively if desired.
I would hope that they could add coverage for new variants to the mRNA vaccines without having to go completely back to square one. Do they have to do full 3 phase testing on the flu vaccine every year?
first issue here is the differences in terminology regarding strains, vs variants.
strains are signifigantly different from each other, variants are a nuance on the same theme.
the virus strain that infects small mammals is separate from the trans specific strain that spilled over to humans.
the virus with small changes to the spike sequence altering spike structure or function is a variant.
under emergency conditions a 3phase trial is not mandatory , and would likely be a quick deliberation under normal conditions for small adjustments to the sequence, similar to seasonal influenza vaccines.