62 ms·
At the risk of starting a flame war, lvs is mostly correct. These are NOT whole gene deletions, they are nucleotide deletions. Genes are usually longer than 33
by entee 6y ago
At the risk of starting a flame war, lvs is mostly correct.
These are NOT whole gene deletions, they are nucleotide deletions. Genes are usually longer than 33 nucleotides, by my count the largest deletion he sees. For reference, that’s 11 amino acids, rule of thumb for an average protein length is about 200 amino acids.
The author highlights that many of these deletions are not codon aligned, which means that if you make this mutation, the resulting protein is highly unlikely to be translated properly. This is true, however devoid of context.
Most of the mutations are very rare. The highest frequency one occurs 400 or so out of at minimum 10,000 examples. Next one is 36/10,000. It’s possible these matter, it’s also possible these viral sequences are just low quality and the mutations are an artifact. It’s also possible that these mutations don’t actually matter to viral function for whatever reason. For example, if the mutation is at the end of a protein, it could screw up everything downstream but the protein before the mutation works just fine, i.e. mutation doesn’t matter. It’s just hard to tell with the data in this article.
The concept that maybe there are attenuated strains isn’t completely bogus, there is some thought a Singapore strain (with a massive deletion of 380 nucleotides, or 10x what we see here [1]) might be less infective. This is speculation and we don’t know yet, but that sounds maybe possible to me as a PhD Biochemist (if we’re gonna get all credential-spreading here).
However saying “The really interesting deletion mutations are those in the non-structural accessory genes. These are the genes that are likely to play an important role in pathogenicity and it would be expected that some of these mutations may make the virus less dangerous (attenuated).” Is really pushing it. I don’t know of any science to believe this one way or another, viruses are pathogenic for a variety of reasons, both accessory and core (whatever that means) proteins matter.
In short, given the uncertainty, we can hope there’s a less infectious strain out there, but this article provides precious little evidence to that effect.
1.) https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.full.pdf https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....
- danieltillett 6y agoLvs is mostly wrong. I am not claiming any of these mutant strains are attenuated, I am saying that deletion mutants exists and we should investigate them to see if they are attenuated. I am not providing evidence that an attenuated strain exists, just evidence that it could exist because the right type of mutations are found in SARS-CoV-2. The only way we are going to find out if there are attenuated strains is to look for them which as far as I know nobody is trying.
- lvs 6y agoSo let's remember how evolution works, shall we? Evolution selects for strains that reproduce the most and selects against ones with attenuated reproduction rates. That's the whole basis of biology. If you've observed a wild strain sequenced in a database, that should be considered direct evidence that it reproduces well enough to have been sampled as a representative isolate. > as far as I know nobody is trying Of course we are. We are deeply engaged in studying the key residues that mediate all aspects of viral infection, reproduction, and clinical pathology. That's another way of saying that an incredible number of researchers have dropped everything to study the genetic and molecular determinants of pathogenicity. Don't worry -- we are on it.
- danieltillett 6y agoWho is “we”? If you are doing this get in contact with me so I can give you money.
- lvs 6y ago> we can hope there’s a less infectious strain out there But how? We are able to surveil only a tiny fraction of genomes, relative to strains circulating. How would a "less infectious strain" ever emerge to the extent we'd have a high probability of sampling it? Darwin argues against this version of the idea. Nevertheless, the OP is also wrong that it's faster to produce a live attenuated vaccine by finding one in the wild than it is to use tried-and-true viral vectors that are easy to reengineer, have previously received regulatory approval, and indeed are already in active trials (e.g. Oxford's adenoviral trial). It's also easier to trial heat-killed virus -- and indeed, that too is being trialed.
- danieltillett 6y agoWe can actually sample quite a large percentage of the strains out there if we actually try. COG-UK has already sampled 10,000 out of the few 100,000s in the UK without really trying. Can you please stop saying I am arguing for things I am not arguing for? More time spent reading and less posting would improve your argument.
- lvs 6y agoYes, there are about 13k genomes deposited in the databses right now, but they are from all over the world -- not just the UK. But yes, given infinite capacity it would be excellent to sequence from every single patient. It would be a dream, but sadly we're barely able to get enough cotton swabs and RNA isolation kits right now to run a basic qPCR for 10% of the population, let alone get all those viral genome sequences. It would be fascinating to have that many, of course.
- danieltillett 6y agoYou do realise that there are over a million positive samples sitting in freezers in the USA alone. You do know that a single modern DNA sequencing instruments can sequence more than 500,000 viral genomes in one 48 hour run?
- entee 6y ago