Phylogenetic tree for coronavirus genomes constructed by the maximum similarity method Lucy van Dorp et al / Nature Communications, 2020 Bri...
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Phylogenetic tree for coronavirus genomes constructed by the maximum similarity method Lucy van Dorp et al / Nature Communications, 2020 |
British researchers have found that, contrary to previous assumptions, the SARS-CoV-2 coronavirus has a rather low genetic diversity, and that none of the identified mutations correlate with an increase in its fitness (in particular, infectivity). To do this, scientists analyzed data on the genomes of the coronavirus accumulated since the beginning of the pandemic. The article was published in Nature Communications.
From the very beginning of the appearance of the SARS-CoV-2 coronavirus in the human population, scientists have been monitoring its genetic variability by determining the sequence of viral genomes isolated from some patients. By the end of July, more than 46 thousand viral genome sequences had been accumulated in various databases.
Researchers periodically suggest that certain mutations can change the properties of the virus and make it less dangerous for humans and/or more infectious. In August, the journal Cell published an article claiming that a mutation in the D614G S protein gene makes SARS-CoV-2 more infectious. In particular, pseudo viral particles with the G-variant multiplied faster in cell culture, and patients infected with this variant showed a higher viral load.
However, bioinformatics from the Institute of Genetics, University College London, led by François Balloux, analyzed the differences in the genome collection and found no obvious traces of selection that would facilitate the spread of any mutations.
Viruses are often characterized by a high rate of accumulation of mutations (you can read about this in our material "The Great Combinator" ), including due to the inability of the enzyme that copies the genome to correct errors. However, coronaviruses cannot be called champions in volatility - their polymerase just knows how to correct errors. Comparing all the available SARS-CoV-2 sequences among themselves, the scientists concluded that the genome of this coronavirus can be called quite stable. Different variants of the virus on average differ from each other by eight substitutions, which is not very much. For this reason, the authors of the article concluded that the SARS-CoV-2 circulating in populations globally belongs to the same lineage, despite attempts to divide it into different groups (which is done mainly in order to trace the transmission of the virus).
In the case of viruses, an increase in infectivity can be assessed as an increase in evolutionary fitness. Then mutations that increase the transmission rate will be beneficial for the virus. According to the law of population genetics, beneficial mutations occur repeatedly and independently in populations. Calculations have shown that there are about four hundred such mutations in the collection of coronavirus genomes. To test whether they lead to an increase in infectivity, scientists calculated a phylogenetic index reflecting the number of "offspring" for each mutation that appeared independently of the ancestral genome of the virus from Wuhan at least three times (there were 185 of them). It turned out that none of the mutations showed any spreading advantages in this way.
Discussing the aforementioned D614G mutation, the authors of the work suggested that its prevalence is more likely due to the "founder effect" since it arose early enough in the ancestral genome, and not to the effect on the rate of transmission of the virus. Based on the results of their bioinformatics studies, they concluded that all mutations in coronavirus genomes are neutral, that is, they do not affect the fitness of the virus. In addition, they drew attention to the fact that a significant part of the mutations is substitutions of cytosine for uracil, which is most likely a consequence of the work of cellular enzymes, in particular, cytosine deaminase, and not viral ones.
