Frist, Omicron learned how to read bit.ly/3texqjz
But it gets weirder ...
Omicron also uses different mechanisms for mutations that change amino acids and those that are 'silent'.
It somehow seems to know what the effect of the mutation is going to be. Amazing.
But it gets weirder ...
Omicron also uses different mechanisms for mutations that change amino acids and those that are 'silent'.
It somehow seems to know what the effect of the mutation is going to be. Amazing.
Let's compare silent and functional mutation statistics for Omicron and the the other variants of concern.
First, silent mutations. Variants have on average 7.1 silent mutations, with a STD of 2.4
Assuming a Gaussian distribution, Omicron looks like it fit right in:
First, silent mutations. Variants have on average 7.1 silent mutations, with a STD of 2.4
Assuming a Gaussian distribution, Omicron looks like it fit right in:
The same analysis for the 'functional', amino acid changing, or 'non-synonymous' (NS) mutations.
Average # of NS mutations for other variants is 23.1 with STD of 10.
Here, Omicron clearly does not belong to the group of other VOCs.
Average # of NS mutations for other variants is 23.1 with STD of 10.
Here, Omicron clearly does not belong to the group of other VOCs.
The ratio dNS/dS, should be a reasonable value. My Monte Carlo simulations of random mutagenesis for SARS genomes came up with an average ratio of 3.5
That is exactly the value for the average of the other variants. Omicron is 6.2, because of the extreme dS value.
That is exactly the value for the average of the other variants. Omicron is 6.2, because of the extreme dS value.
* Correction: extreme dNS value
While analyzing the silent mutations in all the variants on the beautiful website covariants.org I noticed something striking: the large majority of silent mutations are C->T changes. Check it for yourself ...
There are 4 nucleotides (ATGC) that can be mutated into the remaining 3, so there are 12 possible mutations. If they have an equal change of occurring, you expect to see each mutation 8.33% of the time.
But C->T occurs 63% of the time in silent mutations in the variants.
But C->T occurs 63% of the time in silent mutations in the variants.
What is going on here?
Mutagenesis occurs through 2 different mechanisms:
1. When the RNA genome is copied by RNA-dependent RNA polymerase (RdRp), mistakes are made resulting in mutations.
2. "RNA editing" by the mammalian host cell can change the sequence directly.
Mutagenesis occurs through 2 different mechanisms:
1. When the RNA genome is copied by RNA-dependent RNA polymerase (RdRp), mistakes are made resulting in mutations.
2. "RNA editing" by the mammalian host cell can change the sequence directly.
RNA editing is limited to very specific nucleotide changes, and the C->T mutation is a hallmark of a specific class of enzymes (APOBECs) that can convert a Cytosine to a Uracil (C->U), which gets processed like an Inosine (I).
So, apparently more than half of the silent mutations in SARS2 variants are produced by an RNA editing enzyme that changes a C to a T.
The nice thing about silent mutations is that they are *usually* not selected for or against. So they inform unbiased about mechanisms at work
The nice thing about silent mutations is that they are *usually* not selected for or against. So they inform unbiased about mechanisms at work
Interim conclusion:
Half of the mutations in SARS2 are caused by low-fidelity replication (RdRp), and the other half is caused by RNA editing resulting into C->T substitutions.
Half of the mutations in SARS2 are caused by low-fidelity replication (RdRp), and the other half is caused by RNA editing resulting into C->T substitutions.
Because silent mutations aren't biased by selection pressure, they accurately reflect the mechanisms that produce them.
Those same mechanisms should then be responsible for functional mutations.
Are they?
Those same mechanisms should then be responsible for functional mutations.
Are they?
This is where it gets interesting.
In Omicron, the functional/defining mutations have too few C->T mutations. And the difference if shocking.
They are not produced by APOBEC RNA editing.
See picture below. Just look of the density of C>T mutations highlighted in green.
In Omicron, the functional/defining mutations have too few C->T mutations. And the difference if shocking.
They are not produced by APOBEC RNA editing.
See picture below. Just look of the density of C>T mutations highlighted in green.
There are 2 mechanisms for producing mutations:
1.Low fidelity replication.
2. RNA editing
Omicron knows which of these to employ, depending on the effect of the mutation:
Silent (ineffective) mutations use 45% of 1 and 55% of 2.
Functional (effective) mutations use only 1
1.Low fidelity replication.
2. RNA editing
Omicron knows which of these to employ, depending on the effect of the mutation:
Silent (ineffective) mutations use 45% of 1 and 55% of 2.
Functional (effective) mutations use only 1
That is quite smart for a virus, which is basically a piece of RNA code.
Still waiting for the zoonati (you know who you are) to explain this to us.
We will give the zoonati (@stuartjdneil, @macroliter) a couple of weeks (they may be busy) to come up with a good (scientific) explanation for this anomaly.
Hopefully they won resort to ad hominem attacks to hide their insecurities.
Hopefully they won resort to ad hominem attacks to hide their insecurities.
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