Viruses are considered to be the simplest biological entities on Earth, so much so that there is an ongoing debate in the scientific community as to whether or not they can be considered living organisms. But there’s something even smaller and simpler than viruses: viroids, strands of circular RNA molecules that don’t encode proteins but do cause infectious diseases in flowering plants. And just in case we thought these were the last of nature’s weirdest curiosities, in 2024 a new type of biological form was discovered, found within us and yet still a mystery: the so-called obelisks.
In 1922, a potato disease was first described in New York and New Jersey. It was called potato spindle tuber disease because infected potatoes took on this shape and spoilt. It was soon recognised as transmissible, but although the absence of fungi or bacteria suggested a virus, none was found. In 1971, plant pathologist Theodor Otto Diener finally discovered the cause: an RNA molecule, so small that it didn’t contain the genes needed to replicate and lacked the protective protein shell that viruses have. Diener coined the term “viroid” for this pathogen.
Strands of circular RNA molecules still unknown
Diener’s discovery was biology’s third major step into the world of the very small, after the discovery of bacteria and viruses. In the years that followed, the nature of viroids was confirmed: strands of circular RNA molecules with a high base pairing, like a zipper, giving them a physical rod-shaped structure. They are 80 times smaller than viruses, and while the genome of the smallest viruses is less than 2,000 bases (1,000 base pairs in some double-stranded viruses), viroids have only about 250 to 400 nucleotides. But just as viruses carry genes that produce proteins to replicate and infect—although one of the reasons their status as living things is questioned is that they require machinery from the cell—viroid RNA produces nothing.
But if viroids don’t encode any proteins, how do they replicate and transmit themselves? And most importantly, how do they cause disease? As for the former, to make copies of themselves in the cell they invade, they rely on a cellular enzyme called RNA polymerase, which is normally used to create messenger RNA from genes. The viroid’s own RNA has enzymatic activity—hence the name ribozyme, from ribonucleic acid (RNA) and enzyme—to polish the new copies and bind their ends. The new viroids then circulate in the plant’s sap vessels and spread to infect new cells, being transmitted from one plant to another by contact, pollen or seeds. Their pathogenicity is based on interfering with the plant’s own genes by silencing them.
At least 45 species of viroids are known today, divided into two families: the avsunviroidae and the pospiviroidae. All of them infect angiosperms—flowering plants—and cause various crop diseases, although not all are pathogenic. But the nearly fifty known viroids may only be an infinitesimal part of the viroid world out there: by analysing bulk genetic sequences already in databases, researchers have identified more than 20,000 possible viroids or viroid-like entities. And not only is the true diversity of viroids unknown, but their mechanisms are still being studied and will undoubtedly reveal new surprises in the future.
From evolutionary relics to biotechnological tools
To date, the presence of viroids in animals has not been confirmed. But in 2024, a new type of simple biological entity has been added to the catalogue of terrestrial life. Unpublished research led by Stanford University, in collaboration with the Polytechnic University of Valencia and the University of Toronto, has found a viroid-like element in the genetic sequences of the human oral and faecal microbiome, which scientists have dubbed obelisks because of their elongated shape. They are circular RNA strands of about 1,000 bases that, unlike viroids, encode one or two proteins called oblins. Scientists have catalogued almost 30,000 different sequences that would be found in the microbes of our digestive system; their presence has been confirmed in the bacterium Streptococcus sanguinis, a normal inhabitant of the mouth that forms dental plaque.
Almost everything about obelisks is unknown: do they do us good, harm, or nothing at all? What function do they have? But in the context of this increasingly profuse panorama of small genetic elements, which also includes others called virusoids, satellites and so forth, why do they even exist? What is their origin? One hypothesis, long held by scientists, is that life began with a RNA world before the invention of DNA. In 1989, Diener proposed that viroids might be evolutionary relics, molecular fossils from that world before cells existed. Other researchers have supported Diener’s idea, although it cannot be ruled out that these molecules may have originated after the cell.
Scientists are currently attempting to harness viroids as new biotechnological tools: the citrus dwarfing viroid is being tested with the aim of growing smaller trees to increase crop density, and the eggplant latent viroid has allowed the production of RNA with insecticidal activity in bacteria. Between discovery and innovation, genetics at the edge of life is still a vast frontier of scientific exploration.
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