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Scientists uncover propagation mechanism of most common microbiota viruses

The scientists hope that the further research of these viruses and the gp66 enzyme will help to use them in the solution of a number of scientific and medical tasks related to the management of properties of the gut microbiota as well as to manipulations of DNA and RNA

MOSCOW, November 18. /TASS/. Russian and American molecular biologists have discovered an enzyme which helps the most common viruses in the microbiota, the so-called crAss-bacteriophages, to copy their genome and form new viral particles, the press service of Skoltech (the Skolkovo Institute of Science and Technology) reported on Wednesday.

"Since crAss-bacteriophages dominate in the microbiota of the human gut, the understanding of how they infect the microbes will help us manage the content of the microbiota which influences both human health and the nature of development of various diseases," Maria Sokolova, researcher at Skoltech, was quoted by the press service as saying.

Single-cell microbes suffer from diseases and infections much like humans and animals do. The scientists think that viruses emerged almost simultaneously with bacteria and they have been battling for survival with each other for hundreds of millions of years. The consequences of this war can be found anywhere. For instance, every milliliter of fresh or sea water contains hundreds of millions of bacteriophages, the viruses that specialize in infecting microbes. According to current estimates, up to 70% of live bacteria currently may be their carriers. The researchers have been studying their genetics and evolution mechanism for a long time, however, during the past fifty years it was possible to study only a small number of both viruses dangerous to mammals and potentially useful bacteriophages.

A good example of this, as the Skoltech researchers note, are the viruses from the crAss-bacteriophage family which was discovered by biologists only in 2014. Later the scientists uncovered that these viruses dominate in the gut microbiota as well as play an important role in its functioning.

Another interesting property of the crAss-bacteriophages is the fact that until recently the researchers did not know how precisely this virus copies its genetic material, forming new particles inside the infected microbes. As a rule, the viruses use for these purposes the so-called RNA polymerases, special enzymes which read certain DNA molecules and prepare their copies in the form of RNA threads.

Evolutionary traces of viruses

First attempts to find the molecules inside the viruses themselves were not successful. This, however, does not prevent the virus from propagating and dominating in the microbiota. The Russian scientists and their colleagues from the United States attempted to understand how they manage to do this by studying the structure of proteins of one of such viruses dubbed phi14:2.

The scientists discovered a short protein fragment structurally similar to the RNA polymerases of metazoans. Having encountered this molecule which was named gp66, the biologists studied its properties, transplanting the coding part of the viral genome inside a coliform bacterium.

Subsequent experiments demonstrated that this enzyme indeed plays a role of the RNA polymerase, copying single DNA threads. Its mechanism is similar to those enzymes which human cells and cells of other metazoans use for flexible management of gene activity, producing the so-called siRNAs. Those are short nucleotide chains which adhere to copies of certain genes and prevent the cellular protein "factories" from reading them.

"This is a very surprising result which means that those proteins responsible for the functioning of siRNAs in cells of higher organisms could have initially appeared in the bacteriophages. In other words, in distant past our ancestors may have "borrowed" these enzymes from ancient viruses, the ancestors of the crAss-bacteriophages," Skoltech professor Konstantin Severinov added.

According to him, this event was not something unique for the process of evolution of human ancestors who frequently borrowed the enzymes of various viruses and bacteria in their development process. Moreover, the mitochondria, the cellular power stations of sorts, in the past used to be independent bacteria which established symbiotic relationship with the ancestors of the protozoans and the metazoans and ended up being absorbed by them.

The scientists hope that the further research of these viruses and the gp66 enzyme will help to use them in the solution of a number of scientific and medical tasks related to the management of properties of the gut microbiota as well as to manipulations of DNA and RNA.