MOSCOW, July 28. /TASS/. Researchers of the Institute for Information Transmission Problems of the Russian Academy of Sciences have discovered an unusual way of accumulation of point mutations in the SARS-CoV-2 coronavirus genome indicating that recently it was evolutionarily adapted to reside in bats, the Institute’s press service reported on Tuesday citing the article in the PeerJ journal.

"We discovered that the share of mutations of guanine to uracil in the SARS-CoV-2 genome increased almost ten-fold after the virus was transmitted to humans. This characteristic is much less pronounced in the genome of the atypical pneumonia SARS-CoV pathogen and is practically non-existent in the cold HKU1 virus," researchers wrote.

The scientists for a rather long time have been trying to understand where and how the novel coronavirus emerged causing the global COVID-19 pandemic as well as when it started to be transmitted from human to human. There is no consensus among the epidemiologists on this subject.

There are many discussions when and where the first infection of a human with the SARS-CoV-2 coronavirus occurred, whether it shows signs of recombination, whether humans received the virus directly from bats or through a transitionary host as well as why the SARS-CoV-2 turned out to be so strong.

Biologists of the Institute for Information Transmission Problems of the Russian Academy of Sciences Alexander and Yuri Panchin attempted to receive answers to some of these questions, comparing the accumulation of point mutations in the genome of the COVID-19 pathogen with other related coronaviruses - the atypical pneumonia SARS virus and the common cold HKU1 virus. The scientists studied how the relative mutation frequencies changed in those viruses after infecting humans.

A natural virus

In all, Russian scientists analyzed and compared over a thousand SARS-CoV-2 genomes, about two hundred genomes of the atypical pneumonia pathogen, forty sequences for the HKU1 virus as well as several genomes of its closest relatives among the coronaviruses of animal origin.

It turned out that in the genomes of all human viruses approximately one or two thousand point variations are present having appeared presumably after those viruses adapted to infect humans. A study of these small mutations allowed the researchers to uncover a unique characteristic of the novel coronavirus not typical of its closest relatives.

They found that the SARS-CoV-2 genome contains an unusually large number of mutations which lead to the replacement of guanine (G), one of the four "letters" of the DNA and the RNA chains, with the molecules of uracil (U). In all, over two hundred (15%) of the discovered mutations belong to this category. This is almost ten times the share of such mutations in the SARS-CoV-2 ancestor before the infection of humans.

This was absolutely not typical of other coronaviruses in which the share of replacement of guanine with uracil before and after infections in humans was similar. This unique characteristic of the SARS-CoV-2 virus manifested itself both in the full set of genomes and in the analyses of the genome sets obtained in some countries, such as the US and China.

As the article’s authors suggest, this feature of the COVID-19 pathogen reflects the fact that until recently it was infecting bats whose cells are unusually well-defended from the accumulation of various aggressive molecules capable of introducing mutations in the new copies of the viral RNA.

When the SARS-CoV-2 virus moved on to infect humans, it lost this defense, which, as the authors think, led to a damage of a large number of the guanine "letters" of the RNA and the quick accumulation of mutations in the coronavirus genome. The researchers conclude that on the one hand, this is an argument for the natural origin of the SARS-CoV-2 virus, while on the other hand it makes one think why something similar did not occur with the atypical pneumonia pathogen which also originated in bats.