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MOSCOW, February 9, Vladislav Strekopytov. Not a virus, not a genome fragment—scientists have found something unexpected in the human microbiome. Possibly an intermediate link between complex organic molecules and viruses. About this discovery and its significance — in the material .
No longer molecules, but not yet viruses
In the 1920s, American farmers informed scientists: elongated and twisted. It was an infection, but the pathogen was never identified.
Only in 1971, biologist Theodor Diener determined that the cause was not a fungus, not a bacterium, or a virus, but a pathogen of a different, new type, ten times smaller than a virus. The scientist proposed the term viroid, that is, virus-like. As it turned out, more than a third of plant diseases are caused by viroids. Including citrus exocortis, chrysanthemum dwarf, avocado spot, peach latent mosaic and potato tuber spindle.
Viroids are simpler than viruses. These are closed circular single-stranded RNA molecules (sssRNA) ranging in length from 246 to 467 nucleotides. For comparison: there are more than 2000 of them in the genome of the smallest known virus.
The RNA of viroids does not code for proteins, so they do not have the protein shell (capsid) characteristic of viruses and the proteins necessary for reproduction. It is assumed that they use enzymes from the infected cell to replicate. How the infection is transmitted from plant to plant remains a mystery. It has only been proven that this is possible mechanically — for example, through contaminated agricultural tools.
Viroids are everywhere
For a long time, it was believed that viroids live only in the plant kingdom. But viroid-like ssRNAs have been found in animals and humans. Such pathogens include, for example, hepatitis delta virus (HDV). It exists only in conjunction with the hepatitis B virus, using its envelope protein to package its RNA. Although HDV does not spread on its own, it is a serious public health problem. More than 15 million people worldwide are infected.
Last year, an international team of scientists from the RNA Virus Discovery Consortium, led by Evgeniy Kunin from the US National Institutes of Health (NIH), published the results of a unique study. Having developed a computational algorithm for identifying ssRNAs in transcriptomes (RNA sequences), including metatranscriptomes—samples taken from the environment rather than from a specific organism—biologists analyzed 5,131 metatranscriptomes and 1,344 plant RNA sequences. More than 11 thousand cccRNAs were identified, “coexisting” with 4409 species of microorganisms. This is five times more than the total number of viroids known before. It turned out that viroid-like structures are widespread in all environments and types of host organisms — no less widely than known RNA viruses such as influenza, Ebola, hepatitis C, SARS-CoV-2 and others.
The authors acknowledge that their work is only the first attempt to study the world of viroid-like biological structures. Theoretically, millions of variants of circular sequences such as cccRNA and many virus-like combinations of cccRNA and protein-coding genes are possible.
In addition to HDV, such intermediate formations include, in particular, ambiviruses, satellite viruses, and others. All of these are virus-like agents that are larger than typical ssRNAs and encode a protein, but, unlike real viruses, do not yet possess the enzyme necessary for self-replication.
New residents of our body
After the publication of the study, biologists from the USA, Canada and Spain, led by Andrew Fire from Stanford University, decided to test the human microbiome — the totality of all microbes inhabiting our body — for viroid- and virus-like structures. We created a bioinformatics tool and used it to analyze RNA sequencing data of intestinal and oral microflora from the iHMP database, a project of the US National Institutes of Health.
While deciphering the genomes of bacteria, scientists came across a completely new class of virus-like particles, which were called obelisks for their shape. These are symmetrical rods formed by twisted circular RNA molecules about 1000 nucleotides in size.
Obelisks are more complex than viroids — longer and contain codes for specific proteins called oblins. At the same time, they are simpler than viruses, since they do not have genes for the formation of protein shells. Instructions for creating oblins occupy more than half of the oblin genome. These specific proteins are thought to be involved in replication.
By examining 5.4 million published genetic sequences, the researchers identified nearly 30,000 obelisks. They were present in seven percent of gut flora transcriptomes and half of human oral samples. One of the obelisks, 1137 nucleotides long, was associated with a specific bacterium, Streptococcus sanguini, a common microbe that lives in the mouth.
“We do not yet know the owners of other obelisks,” write biologists. “It is reasonable to assume that at least some of them are in other bacteria.”
How obelisks affect human health is unknown. Theoretically, they can change the genetic activity of their bacterial hosts and affect human genes.
The smallest particle of life
Scientists still cannot decide whether to classify viruses as living beings — after all, they are not able to reproduce on their own. And now even simpler forms of “half-life” have been discovered.
The question remains open in which direction evolution was moving — whether viruses originated from more complex viroids and obelisks, or whether viruses degenerated into more primitive biological particles.
Neither in structure nor in RNA sequence are obelisks similar to anything else and form a separate phylogenetic group.
These fragments of genetic material are too short to be considered a standard form of life, but they clearly represent one of the smallest and most primitive biological formations capable of reproducing and transmitting genetic information. And these are the most important signs of living organisms.
Perhaps obelisks are a transitional link between molecules and viruses, a remnant of the ancient RNA world, from which the history of life on Earth is believed to have begun.
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