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