Het moet toch niet gekker worden! De zwartkop is een trekvogel en overwintert in Zuid-Engeland, Spanje, Marokko en Algerije. Het is een zangvogel en insecten-eter. Hier zit ze bessen van de klimop te eten. Ik vond meerdere winterwaarnemingen in Nederland! Nieuw voor mij.
Zanglijster. 10 feb 2021
Zanglijster lijkt wel een beetje op de koperwiek, maar heeft geen rode flanken en geen duidelijke lichte oogstreep. Ook lijkt de zanglijster een beetje op een vrouwtje merel, maar de zanglijster heeft een veel lichtere borst.
There seems to be a competition between countries to report new SARS-COV-2
variants. The media try to make sense of it and try to answer questions about how
dangerous these new variants are. For example, the
Scientific American: The Most Worrying Mutations in Five Emerging Coronavirus Variants [1] and The Scientist [5].
This is a very useful article. I will return to it. But there are more variants and many more mutations. What is the total number of different mutations that have been found worldwide up to
now? Answer:
NCBI virus database
[2]. The NCBI started an overview of all mutations in SARS-CoV-2. This is free information and no account is required. This is a user-friendly website.
After a few seconds a table with all mutations appears with columns. See appendix for the columns in the list.
Explanation
A non-synonymous substitution
is for example:
D614G
is : amino acid D is replaced by G in position 614
in the Spike (surface glycoprotein). The 614 position is relative to the start
of the first amino acid (AA) of the protein. For the Spike protein the
position is between 1 and 1273. That is the length of the protein. The Spike is a relatively small protein.
The
genomic position is a number between 1 and 29,903. That is the length of the standard reference SARS-CoV-2 genome.
Asynonymous substitutionfor example:Q613
Q. Q 'replaced' by Q. This is still a substitution
because the substitution is at the nucleotide level: CAA > CAG. The nucleotide change is listed also in the table.
The Count gives an indication whether the mutation is rare. In Collected
location the countries of origin of the virus sample are specified.
Furthermore, a handy feature is that each
column can be sorted (up/down) by clicking on the header. Try it!
There are not yet statistics provided by the NCBI website. I counted (30 Jan) the
number of mutations in Spike protein (surface glycoprotein):
264 non-synonymous mutations
345 synonymous mutations
609 mutations total
This is expected: there are more synonymous than non-synonymous mutations. This is quite a lot for a protein of 1273 Amino Acids: 20% Amino Acid changes and 47% of the Spike nucleotides have mutations. The million dollar question is what the effect is on the behaviour of the protein and the properties of the virus. A first step is:
From one-dimensional RNA to three-dimensional proteins
A spectacular and sophisticated feature is the interactive 3-D display of
the protein which is shown when clicking on the link of the Protein Change. Try it!
By moving the mouse pointer over the protein, the names of individual
Amino Acids with position are displayed. The software is keeping track of all 1273 Amino Acids in this very complicated 3D structure! Really great software! After a lot of trial and error I found the ASN501.
ASN = Asparagin; 1-letter code: N.
Tip: for the table of code names for amino acids see this page.
Asparagin on position 501 (N501) is the location of the famous mutation
N501Y. N is replaced by Y.The amino acid it is marked by a yellow color:
zoomed in. Yellow structure is Asparagin in position 501
Not surprisingly, the yellow position 501 is located on the outside of the molecule. It must attach to the human ACE2 receptor. It could not work if it were located at the inside of the molecule.
Try it. Play with it. Move the cursor over the structure. Manipulate the point of view with your mouse by holding the mouse button down and move. Watch the different angles of view. Try other mutations. (click on other mutations in the main table). Zoom in. Mind you: this is the molecule that caused a pandemic!
Remember: the three-dimensional structure of a protein is the first step in discovering the effect of a mutation.
Problems: Not all links to 3D proteins seem correct. H1000Q results in a protein THR257. The links are made manual?
Later I discovered that one can select certain locations in the one-dimensional RNA (in the right panel of the page) and the selected amino acid will appear yellow highlighted in the 3D model. I have to explore that.
The famous N501Y mutation is found in the variant in UK, South Africa and Brazil. Here is the list of the Scientific American article [1]:
Spain: A222V (Spike) -
UK:
- - N501Y (Spike)
South Africa: E484K K417N N501Y
[virus escape mutant]
Brazil:
E484KK417N/T N501Y
Universe too small ! too short living !
The number of possible proteins of length 1273 is staggering. Do the calculation: for every position there are 20 possibilities because there are 20 Amino Acids. "So there are 20×20 = 400 distinct proteins of 2 Amino Acids, 20x20x20 = 8000 proteins of length 3 AA, 160,000 proteins of length 4 AA, 3,200,000 with just 5 AA." [4] etc. Total: 20^1273 AA
sequences for the Spike alone. And that is only one protein! Obviously, evolution could not have tried out all those possibilities. The age of the universe is too short to try them all out! So, we can expect endless new virus variants coming as long as we don't interfere with the pandemic and the virus is allowed its natural course.
After discovering two immuno-compromised patients with high mutation rates and accelerated evolution, I remembered that the original publication describing the highly transmissible British SARS-CoV-2 B.1.1.7 variant, also discussed immunodeficient or immunosuppressed patients [1]. They discussed such patients for a good reason. They were puzzled with the unusual high number of mutations present in the B.1.1.7 and the fact that they did not see any precursors of the variant. Usually, there must have been a step by step accumulation of mutations. But the B.1.1.7 variant made a big jump in sequence space. They asked: What evolutionary processes or selective pressures might have given rise to lineage B.1.1.7 ? They noted that an accumulation of many mutations in immunocompromised patients has been reported in the literature. This could also be an explanation of the origin of the B.1.1.7 variant. This is what they conclude:
"These considerations lead us to hypothesise that the unusual genetic
divergence of lineage B.1.1.7 may have resulted, at least in part, from
virus evolution with a chronically-infected individual. Although such
infections are rare, and onward transmission from them presumably even
rarer, they are not improbable given the ongoing large number of new
infections.
Although we speculate here that chronic infection played a role in
the origins of the B.1.1.7 variant, this remains a hypothesis and we
cannot yet infer the precise nature of this event."
If this is true, then the highly transmissible British variant originated in one sick individual! One person is the source of a highly transmissible variant that conquered the world and caused severe lock-downs all over the world. Some talk even about a second pandemic.
Knowing this, it seems urgent that these immuno-compromised patients with covid-19 once released from the hospital must be kept in quarantine for a few weeks in order to prevent the spread of a dangerous new variant.
Together with another case [2] there are possibly 4 cases of immunocompromised patients with high mutation rates. The 4th patient (supposed to be the origin of B.1.1.7) is inferred to exist, but has not been identified as far as I know.
Furthermore, if true, this shows that within-host evolution of the virus does not prevent being a better between-host transmitter.
