Nature still hides huge surprises. A team of seven scientists — including two Spaniards and the American Nobel Prize winner Andrew Fire— has discovered inside the human being a new “biological entity”, on the border of what is considered life. These elements, called obelisks and even simpler than viruses, are infectious agents that apparently colonize some bacteria in people’s mouths and intestines. Its alleged impact on human health, harmful or beneficial, remains to be elucidated. “The obelisks are unclassifiable,” says the virologist Marcos de la Peñaco-author of the discovery.
The researchers have detected obelisks in half of the 32 mouths analyzed and in 7% of the feces of 440 donors. De la Peña himself asks himself an obvious question: “How the hell has no one seen it before?” The instruction manual present in each of a person’s cells, their DNA, has about 3,000 million letters. Faced with this unimaginable complexity, the obelisks are a stretched circular molecule that barely has a thousand letters of another type of genetic material, RNA.
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The new biological entities are so simple that they could have played a role in the origin of life on Earth about 4 billion years ago. The Spanish virologist remembers the RNA world hypothesiswhich proposes that these versatile molecules functioned as the first heritable genetic information in primitive organisms. “We believe they have been with us for a long time,” explains De la Peña, from the Institute of Molecular and Cellular Biology of Plants, in Valencia. “Structurally, they look like they are one of the oldest elements on the planet. They have all the classic characteristics of what would be the primordial RNA world. These animals “They have all the credentials to have been there from the beginning,” he adds.
The astonishing discovery is published this Wednesday in the specialized magazine Cell. The authors have identified 30,000 species of obelisks, but so far they have only been able to associate one of them with a specific bacteria, the Streptococcus bloodtypical of the human mouth. De la Peña emphasizes that this opportunistic microbe can access to the bloodstream and cause inflammation of the heart. “These infections can even be fatal. We are seeing that only some strains of Streptococcus blood They have obelisks, but so far we have not detected a correlation [con su gravedad]”says De la Peña, belonging to the Higher Council for Scientific Research. The seven signatories emphasize that they do not know the hosts of the rest of the obelisks, but they assume that other bacteria will also harbor these mysterious elements. Each microbe can store more than 1,000 obelisksaccording to a calculation by two scientists from Duke University, in the United States.
American biologist Andrew Fire won the Nobel Prize in Medicine in 2006 after demonstrating that small RNA molecules can inactivate specific genes. Fire, from Stanford University, recognizes the unknowns: How to define obelisks? Are they really infectious agents? What is its effect on human beings? Could they have applications in medicine? Are they vestiges of the origin of life on Earth? “The answer to each of these questions is that we don’t know yet,” he says.
Your colleague Ivan Zheludevalso from Stanford, has consecrated his doctoral thesis to the obelisks. The doctoral student proposed naming them that way because their stretched shape reminded him of Cleopatra’s Needles, the famous Egyptian monuments relocated to his native London and New York. On January 21, Zheludev and his six co-authors published a first draft with their preliminary results, but had refused to make statements until now.
Artistic recreation of the obelisks inside a bacteria.IBMCP (CSIC-UPV) (Made with Google AI)
The biologist María José López Galianoco-author of the work, believes that the discovery of the obelisks opens the door to potentially revolutionary applications. “These molecules behave in a different way than anything we know so far. We have tried to understand how they interact within their host, with the bacteria Streptococcus blood in the lab, but we don’t really know what they’re doing. We do not know if the obelisks confer any advantages over the rest of the bacteria, such as resistance to some type of antibiotic,” says López Galiano, from the University of Valencia. The biologist speculates with the idea of using them in some way to counteract the loss of effectiveness of antibiotics. Multi-resistant bacteria cause 33,000 deaths per year only in Europe.
The biologist Gustavo Gomez Remember that, historically, RNA molecules have been considered mere transmitters of the information contained in DNA. Each cell has two meters of DNA folded in an implausible way in its tiny nucleus. To extract this information, cells copy these instructions and write them in another language, that of RNA molecules, capable of leaving the cell nucleus and directing the manufacture of proteins, the true protagonists of life. “Various discoveries made in the last two decades have shown that RNAs can fulfill complex regulatory functions, becoming, according to some theories, one of those directly responsible for the biological complexity in organisms,” says Gómez, director of the Institute of Integrative Systems Biology, in Paterna (Valencia).
In the opinion of this biologist, who has not participated in the research, the discovery of the obelisks, so closely associated with the environmental and human microbiome, “further highlights the biological potential of RNAs.” For Gómez, these new biological entities “contribute to the fact that the line between what we know today as living and what is inert is increasingly less defined.”
Viruses were the frontier of life until 1971, when it was discovered that potato spindle tuber disease was caused by even simpler infectious agents, which were called viroideswith about 300 RNA letters. De la Peña recalls that only about 50 viroid species were known in plants and animals until 2023, when an international team, in which he himself participated, revealed the existence of another 20,000 typesamong which there were already some obelisks in samples collected in nature.
The virologist Guillermo Dominguezfrom the Spanish Institute of Oceanography, believes that the new study is another step in the race to carry out “ambitious bioinformatics searches” in the genetic material found in soil, estuary and ocean samples. “Since approximately 2015, we have witnessed an expansion in the diversity of parasites whose genome is made of RNA instead of DNA,” he explains. “All this suggests that what has been discovered so far is still the tip of the iceberg, a tiny percentage of an RNA virosphere that could gather more than two billion species of RNA viruses,” says Domínguez, citing his own calculation.
“Traditionally, viroids had been a few species, all of them parasites of plants such as potatoes and avocados. “Parasites so simple that they do not encode proteins or have a capsid, without extracellular life, that are transmitted from one plant to another vertically through generations,” he explains. “These strange parasites have remained in the shadow of the anecdotal cases of virology, awakening only the interest of phytopathologists and evolutionary biologists interested in vestiges of the precellular RNA world. In the last three years, more work has emerged where bioinformatic strategies are enhanced to detect these cryptic parasites in the infinite number of sequences available today in databases, detecting new types, such as zetaviruses and obelisks,” adds Domínguez. “We still do not know how extensive the effect of these viroids and viroid-like agents can be infecting bacteria in our microbiome and on our health, but it is undoubtedly a promising discovery that can open the way to better understand the microbial ecosystem with which we live. “, sentence.
The virologist Marcos de la Peña participated in another great discovery in 2022: the identification of 132,000 new virus species, including nine coronaviruses, thanks to a new computer tool capable of combing gigantic genetic databases, such as those from hospitals and ecosystems. natural. Despite these successes, De la Peña says that the State Research Agency, dependent on the Ministry of Science, has just refused to finance a project to continue investigating this enigmatic new world of RNA. The virologist believes that it is easier to receive public money by producing many mediocre studies, rather than a few quality ones, with co-authors such as Nobel Prize winner Andrew Fire. “Doing top-level science in Spain is tremendously complicated. It seems that the only thing that counts is being the one who scores the goal in the Second or Third division and it is worthless to win in the Champions League after putting together top teams,” he laments. Next year, he says, he will have zero euros to research.
