In early February, a first alert was issued from the United States, during a conference reported by the magazine New Scientist, over one recombination of an “English” variant with a local one, but without confirmation since then. A “hybrid” virus, as a result of the highly transmissible B.1.1.7 variant discovered in the UK and B.1.429 originating in California, was believed to be responsible for a wave of cases in Los Angeles given one more mutation. resistant to some antibodies.
Now, the team responsible for sequencing and its analysis, the COG-UK consortium, revealed on the specialized site Virological.org the first 11 recombinations in the history of this young virus, divided into four groups, with each two or three identical representatives. Four other “putative” hybrids present in a single copy are also described.
What are these combined mutations?
They are part of a biological cycle. Like their predecessors, they are ways of increasing genetic diversity, in this case of a virus, and, therefore, of obtaining different behaviors that are more appropriate to their environment and survive. Recombinations, according to the specialists, are chimeras, made of two segments of genomes joined and taken from two different lines of SARS-CoV-2. They could also be explained as the creation of a virus from two others.
The warning, as happened with the first variants, came from the United Kingdom. The COG-UK consortium researchers explained that all of these changes have sequence bits from the variant identified in late 2020 in England, named “B.1.1.7” or “501Y.V1”. The rest is made up of two “old” lines. At the beginning of February, a first alert had been issued from the United States, about a “mix” between the “English” variant with another “Californian”.
At the time, Bette Korber, from Los Alamos National Laboratory in New Mexico in the United States, and responsible for this finding, was the discoverer of what was to be the first combined mutation of the two genomes since the coronavirus pandemic began.
Unlike the normal mutation, where the changes occur one at a time, which is how “British”, “South African” or “Brazilian” variants arose, recombination can join multiple mutations at the same time. Most of the time, these do not confer an advantage on the virus, but sometimes they do.
According to François Balloux of University College London, recombination “may be of great evolutionary importance”, even considered by many to be the way in which SARS-CoV-2 originated.
Something normal and frequent
Recombination is a frequent and well-documented feature of the molecular evolution of coronaviruses, says published work. Recombination probably occurs in all infected individuals, but in almost all cases the recombination will be between nearly identical genomes (descendants of the small group of viruses that established the infection).
Recalling that bats harbor, without risk, a large amount of coronavirus, for Hubert Laude, veterinarian, pioneer in coronavirus research, SARS-CoV-2 “are champions in intergenomic recombination, who like to recombine within them to acquire new functions.”
These “copies” take place when an enzyme, polymerase, “reads” the viral RNA strand joining it to emulate it. This process can go wrong, with a polymerase slowing down, stopping, and taking another thread to copy, adding this new sequence to the old one.
“SARS-CoV-2 has a longer genome than other viruses, which increases the chances of accidents. Its polymerase is also less “tight” in the strands “, adds Bruno Canard, research director of the National Center for Scientific Research (CNRS), at the University of Aix-Marseille, and collects the French newspaper” Le Monde “.
Where is COVID-19 headed?
The phenomenon is not strange. Recombinations are frequent, to the point that it is undoubtedly due to this mechanism that one of the key proteins of SARS-CoV-2, the spicule, appeared.. Analysis of the pangolin genome revealed that one end of its spike had been acquired by recombination; However, explaining, despite the similarity, the adaptation and the passage to the human, is not so clear.
But only a fine statistical analysis makes it possible to distinguish what would be the result of an accumulation of mutations. English researchers rule out errors in their analysis. Recombinations can be done very well in vitro, during the various stages of sequencing, which amplify and disrupt genomes. However, the detection of these recombinants in different laboratories, and with cuts in exactly the same place in the sequences, allows them to have confidence in their identification. To the point that they do not hesitate to “anticipate” the discovery, suggesting and baptizing these mutants by adding the letter X.
For recombinations to occur, there must be coinfections, that is, a cell from the same individual is infected with two different strains at the same time. While the detection of clear examples of recombinant SARS-CoV-2 genomes in the UK is a consequence of the distinction of the lineages involved and the intensive genomic surveillance in the country, the frequency of coinfection will depend on the incidence. and the co-circulating lineage in a region.
“Given that several countries are experiencing impacts as strong as the UK at the end of 2020, We predict that recombinations will be detected more frequently if intense sequencing efforts are maintained”Describes British work.
“The arrival of recombinants was expected, but it will not have immediate consequences in the trajectory of the epidemic” , the researchers say in the article. Replacements by ‘new copies’ are primarily the result of error-prone replication, and are not expected to have an effect, most recombination events are simply the result of processes within the ‘host’ that occur with each infection. .
Finally, the study maintains that this recombination probably occurs in all infected individuals, but in almost all cases the recombination will be between almost identical genomes. Its rarity advocates the absence of a more communicable character, for example. Nevertheless, the same document recognizes that a recombination can also mutate and generate a problematic variant, which makes observation and analysis central for possible recalibrations of the vaccines created.