There is no significant news on the topic of vaccines of concern to everyone, but I am sure they will appear soon. I decided to “fill the gap” with a post about the variability of SARS-CoV-2. The words “mutation”, “mutant”, not without the help of the media, have a terrifying effect on the general public. And “sensations” in this area appear regularly … I warn you, this post is difficult to understand, apart from the very beginning.
As the virus multiplies, mutations are generated constantly. In the case of SARS-CoV-2, viral RNA copying errors play a major role in this. But they rarely happen. The fact is that SARS-CoV-2 has a “special” RNA-dependent RNA polymerase capable of correcting errors made by it. Some, but not all! There are other mechanisms of mutation (genetic recombination, cellular systems of “RNA editing”). But, regardless of how the mutation originated, it is essentially a change in the sequence of nucleotides in genomic RNA.
The RNA genome of SARS-CoV-2 contains approximately 30 thousand nucleotides. The “canonical” genome of SARS-CoV-2 is the sequence of the first “ Wuhan ” isolate of SARS-CoV-2, identified by Chinese researchers and made publicly available at the beginning of January 2020. By the way, this is what allowed everyone to start developing diagnostic tests and vaccines almost immediately . If the genome of the SARS-CoV-2 variant under study has at least one difference from the ” Wuhan ” genome, it is a mutant. Recently, the results of the most complete analysis of the genomic diversity of SARS-CoV-2 have been published. Of particular interest is the evaluation of the infectivity of various SARS-CoV-2 mutants contained in this work .
46,723 SARS-CoV-2 genomes from 99 countries were analyzed (the length of each sequence is 29903 nucleotides). Differences from the genomic sequence of the Wuhan isolate were identified at 12706 genomic positions. Accordingly, 17197 genomic positions were constant. This does not mean that mutations at these genomic positions do not occur at all. It’s just that these mutations reduce the viability of the virus so much that its offspring are “out of the game.” With a random selection of pairs of isolates from this dataset, the average number of differences between them was about 8. On the one hand, this means that there are almost no 100% identical SARS-CoV-2 isolates . But on the other hand, compared to other viruses, the degree of genetic diversity is low and there is reason to believe that the evolution of SARS-CoV-2 is rather slow and dramatic changes in its biological characteristics are unlikely.
Evolutionary trajectories can be reconstructed using phylogenetic analysis. This is a very special and complex area of evolutionary biology. It will not be possible to understand this on the fly. But the end result of this analysis is intuitive. This is a phylogenetic “tree”, the branching of which corresponds to different “genetic lines”. The phylogenetic tree “grown” in this work includes 46732 “twigs” intertwining into branches of various thicknesses and lengths.
Isolates from different continents are marked with different colors. Of course, looking at this figure, it is impossible to draw any conclusions, except that the tree has branches and they are not monochrome, i.e. isolates from different continents are scattered along different branches. A detailed analysis of this phylogenetic tree showed that although some genetic variants have “geographical preferences” (branches with a predominance of one color), in general, the entire genetic diversity of SARS-CoV-2 is represented on every continent . In other words, having only the genomic sequence of the SARS-CoV-2 isolate, it is impossible to unambiguously determine where it was “hooked up”, although some probabilistic estimates are possible.
I am approaching the main and most difficult thing – the assessment of the “infectiousness” ( contagiousness / transmissibility ) of various SARS-CoV-2 mutants. It is logical to assume that if the same mutations arose independently (in completely different branches of the tree) two or more times, then they have selective advantages. In evolutionary theory, these mutations are called ” homoplasies .” If among the genetic variants of SARS-CoV-2 there are those that are more infectious, it is most likely to find them among the homoplastic mutations . About 400 of them were identified in this work . But how can the degree of infectivity be estimated using phylogenetic analysis tools? This is not a trivial task, but it was solved. The details are too complex for a layman. The bottom line is to calculate more often or not mutants – homoplasies give “daughter shoots” in the phylogenetic tree. It turned out not. None of the SARS-CoV-2 mutants showed any indication that their transmissibility was increased. This conclusion is valid for the data accumulated by September 2020. It is impossible to exclude the appearance of a more infectious variant in the future. And the branches of the phylogenetic tree will gradually isolate *** sya that, in particular, can lead to the emergence of different antigenic types of SARS-CoV-2. But, apparently, this process is rather slow, which provides a rather wide “window of opportunity” for vaccines developed on the basis of the “canonical” genomic sequence of SARS-CoV-2.