08 April 2021

Less is More. How removal of a few amino acids in the SARS-CoV-2 spike protein outsmarts the immune system

People systematically overlook subtractive changes. People tend to solve design challenges by adding extra elements even when taking something away would be simpler and more advantageous, according to an article in Nature today [1]. 


It took decades to think of removing pedals,
rather than adding stabilizers
[2].

Common wisdom tells us that deletions in human texts cause loss of information. Almost by definition. The message is damaged. But is this wisdom also valid in genetic texts?
 
Enter the SARS virus. 
 
Can a deltion  in  genetic material have a positive effect? 
Can a deletion in genetic material have a positive effect? 
Variants of SARS-CoV-2 show the answer is: YES.

In January I blogged about the highly transmissible British variant [3]. This variant suffered from no less than 3 deletions [4]. Two occurred in the Spike protein. The British variant did not seem to be handicapped very much. On the contrary. At the time I didn't pay attention to the remarkable fact that deletions contributed to a positive effect. It didn't struck me as odd.


three deletions highlighted from [3].


Now I see that those deletions have a beneficial effect for the virus. (Not for us!). Nucleotide deletions in a specific part of Spike protein of SARS-CoV-2 may alter antigenicity. That means they normally provoke an immune response in the body. In this case that immune response is weaker. Specifically, deletion of amino acids 69 and 70 in the British variant B.1.1.7 resulted in a substantial higher infectivity of the virus. So, these the deletion of these amino acid seem to improve SARS-CoV-2 fitness. Deletion of amino acid 144 in B.1.1.7 variant and amino acids 242-244 in B.1.351 variant have also been associated with reduced binding capacity of certain neutralizing antibodies, and thus have a beneficial effect for the virus [5].


How can this LEGO structure be stabilised? [2]

When confronted with this LEGO structure with a blue supporting block in the left corner (see picture), and asked to stabilize the structure, most people add three supporting blocks in the remaining corners, but some simply removed the blue block. A simple and perfect solution. See video [2].

Evolution, found the same solution by trial and error. By removing a few amino acids, the virus has been improved.

I found the examples from everyday life helpful and inspiring. If you liked them too, please forward this blog post to your friends!

Fingerless Gloves (source)

Fingerless gloves: surprising result when you delete parts of the age-old design of a glove! Fingerless gloves are useful where dexterity is required that gloves would restrict. Cigarette smokers and church organists sometimes use fingerless gloves.


Postscript

In defense of the adding stabilizers to the bike: it's easier to add temporary stabilizers because they can easily be removed. So, one can use the same bike when the child is older. In contrast to the balance bike (loopfiets) where the pedals and chain, etc has to be removed. But that is a redesigned bicycle. But indeed, it is a much simpler bike! [21 Oct 2024]

 

Notes

  1. People systematically overlook subtractive changes, Nature 8 April 2021
  2. Less is more: Why our brains struggle to subtract, youtube 7 April 2021
  3. Finding the highly transmissible British SARS-CoV-2 B.1.1.7 variant in the USA, blog 7 Jan 2021
  4. Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape, Science 12 Mar 2021 
  5. SARS-CoV-2 Variants vs. Vaccines, American Society for Microbiology, March 3, 2021.
  6. "The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the Spike protein " 18 Mar 2021


06 April 2021

Seks bij pimpelmezen en heggenmussen. 6 april: zon en sneeuwbuitjes

Vanochtend 6 april 2021 zon afgewisseld met sneeuw- en hagelbuitjes. Vorige week dit:

boven: mannetje pimpelmees,
onder: vrouwtje


Als een pimpelmees paartje een nestkast gekozen heeft en nestmateriaal aanslepen, let dan de dagen er na goed op het vrouwtje. Wanneer het vrouwtje met trillende uitgespreide vleugels op een tak zit, dan is dat signaal voor het mannetje. Houd je camera gereed!

pimpelmezen op heter-daad betrapt (27 maart)

Ook hier heb ik het moment-suprême niet kunnen vastleggen. Net als bij de Turkse tortels in een vorig blog. Het is in ieder geval een paring waarvan we niet weten of er bevruchting heeft plaats gehad.

soort naspel

Na de daad zie je een soort naspel. Tenminste daar lijkt het op.

 

heggenmus verzamelt nestmateriaal (mos) 17 mrt

links: mannetje. rechts: vrouwtje heggenmus


Als je het vrouwtje heggenmus voortdurend met vleugels en staart ziet trillen terwijl ze op de grond zit, en het mannetje is in de buurt, pak dan je camera. Je ziet dan een hoogst bizar tafereel. Het mannetje gaat pikken op de plaats van het cloaca van het vrouwtje. Dat duurt een tijdje. Er wordt gezegd dat dit zou zijn om te zorgen dat het zaad van een vorige paring uitgeworpen wordt. Ik heb nog geen bewijs gevonden. Ook nog geen wetenschappelijke publicaties. Als iemand een publicatie kent, dan hoor ik het graag! Je verwacht dan dat er onmiddellijk daarna een paring plaats vindt. Die heb ik niet gezien. Het mannetje verdween. Ook in een filmpje op youtube volgt er geen paring.

Het is wel waar dat het heggenmus Prunella modularis vrouwtje met meerdere mannetjes paart (Polyandrie). Het vrouwtje heeft dus wel een motief. De vraag blijft als dat pikken naar de cloaca een succesvolle methode is, en het vrouwtje werkt er aan mee, waarom zou het vrouwtje dan met meerdere mannetjes paren? Voor de zekerheid en om de kans op een beter mannetje af te wachten?

Ik heb van het hele gebeuren een video (moet nog ge-edit worden), die zal ik later posten.

Krentenboom begint uit te lopen en te bloeien.


Pimpelmees (nl wikipedia), Eurasian blue tit (Engelse wikipedia)

Heggenmus, Engels: Dunnock (wikipedia)


29 March 2021

Strong evidence that SARS-COV-2 variants recombined in several persons in the UK

 

 

Corona update 29 Mar 2021

 

 

 

 

Recently researchers from the UK discovered recombinant SARS-CoV-2 viruses in several infected persons [1]. The recombinants consist of the now dominant British variant B.1.1.7 with several other variants. That viruses in the wild recombine is an important finding, because it proves recombination in SARS viruses is real and –importantly this could throw light on the origin of SARS-CoV-2 itself. 

Fig. 1. Different recombinant SARS-CoV-2 viruses
(adapted from Ben Jackson et al)
Top row (grey) displays the genes,
bottom row displays base position (1 – 30.000)

(click to zoom)

In the publication is a two-colour illustration of the genomes of 8 SARS-CoV-2 recombinants. In order to distinguish them easily, I added colours to the variants, each variant its own colour. Related variants similar colours.

The sequences reveal that some genome sections carry mutations characteristic of B.1.1.7, whilst other sections carry mutations specific to another lineage. That is fortunate, because it makes it possible to distinguish the segments.

As can be seen from the figure the British variant B.1.1.7 (blue) recombined with one of 6 other variants. Not with more than one other variant. Theoretically, a virus could carry sections of 3 or more parents.

The resulting recombinant viruses could be called hybrid or mosaic viruses. They are intact, can multiply and can infect other people. This can be concluded from identical recombinants in different people (groups A-D in figure 1).

The authors were able to locate the breakpoints within a region of hundreds to (in some cases) a few thousands bases accuracy. It all depends on the availability of marker mutations. If markers are evenly distributed, breakpoints can be more precisely determined.

Could the recombinants be artefacts?

It could be. But, from the fact that recombinant groups A-D are found in samples from different infected people, the authors conclude that it is highly unlikely that these sequences are artefacts. They present further details to support the claim the recombinants really are present in people infected with two SARS-CoV-2 variants (co-infection). As good scientists, they consider alternative explanations.
 

Is recombination rare?

No, presumably it occurs in every infected individual, but can not be detected if there is only one SARS-COV-2 variant present. To detect recombination, there must be different variants present in the same person.


Does recombination occur in other animals?

A bat has been observed harboring several different coronaviruses. Coronavirus co-infection was detected in six bat species, a phenomenon that fosters recombination and promotes the emergence of novel virus strains [4]. 

 

Is recombination unique for viruses?

No, recombination routinely occurs in sexually reproducing organisms at the moment female and male sex cells are produced.


Is the recombinant virus more dangerous?

At the moment there is no evidence that recombinants are more infectious or pathogenic.

 

Are recombinants mutations?

Yes, recombinants are mutations because new virus particles are produced that differ from their parents. But in stead of one base is replaced at a time, resulting in one amino acid being replaced, by recombination existing mutations are combined in one virus in a new way. The combination of mutations could have a strong effect on virulence or pathogenicity of the virus absent in individual mutations. It would take a long time for such new combinations to happen by a series of single-base mutations. But by recombination it happens in one step. It accelerates evolution. Recombinants can be advantageous, disadvantageous or neutral for the virus.

 

Does it throw light on the origin of SARS-CoV-2?

On 1 July 2020 an article appeared in Science: 'Recombination plays an important role in the evolution of Corona viruses' [3].  The authors conclude: "Here, we demonstrate, (...) a complex pattern of evolutionary recombination and strong purifying selection between CoVs from distinct host species and cross-species infections that likely originated SARS-CoV-2." [3]. "All three human CoVs (SARS, MERS, and SARS-2) are the result of recombination among CoVs."

The only problem is that the parent species of that fatal recombination event still have to be found. But that is not impossible.



Update 2 April: 

Publication [3] replaces this publication: Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins, Nature, 7 May 2020 because it has issues.



Notes

  1. Recombinant SARS-CoV-2 genomes involving lineage B.1.1.7 in the UK, 17 Mar 2021. virological.org
  2. Two coronavirus variants have merged – here's what you need to know, NewScientist, 17 Feb 2021
  3. Emergence of SARS-CoV-2 through recombination and strong purifying selection, Science 1 Jul 2020 
  4. Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft, 18 February 2016 . Added 3 April 2021