An international team of seven scientists, including two Spaniards and Nobel Prize winner Andrew Fire, has discovered new biological entities called "Obelisks" in the bacteria that inhabit the human mouth and intestines, at the border of what is considered life. The details of the finding were published in the journal Cell. These minimal biological entities challenge the understanding of the limits of life and have been detected in half of the 32 mouths analyzed and in 7% of the feces of 440 donors.
Obelisks are simpler than viruses, consisting of a stretched circular molecule with about a thousand letters of RNA. They are infectious agents that appear to colonize some bacteria in the mouths and intestines of humans. Virologist Marcos de la Peña, a co-author of the discovery, states, "The obelisks are unclassifiable." Their unique characteristics place them between viruses and tiny viroids, without being either type of infectious agent.
These RNA circles are highly self-complementary, allowing them to adopt a stable rod-like structure reminiscent of the Egyptian monuments that give them their name. Obelisks are named for their elongated rod shape. They lack the protein coat that characterizes viruses but, like viruses, they are capable of coding proteins. Marcos de la Peña explains, "We know that the simplest RNA viruses need a genome size greater than 3,000 nucleotides, but the obelisks barely exceed 1,000, well below that of viruses, but that, however, allows them to code one or two proteins."
The study, conducted through bioinformatics analysis, discovered that these new biological entities are part of the human microbiome. Analysis of further datasets revealed that obelisks are globally distributed members of human oral and gut microbiomes, discovered through bioinformatic analyses. Obelisks have been associated with the bacterium Streptococcus sanguinis, typical of the human mouth. The authors were able to show that Streptococcus sanguinis, a commensal bacterium of the oral microbiome, harbors an oblin 1-encoding RNA called Obelisk-S.s. Under replete growth conditions, Obelisk-S.s was shown to be dispensable for the growth of Streptococcus sanguinis. This suggests that Streptococcus sanguinis is a replicative host for the obelisk RNAs.
The function and effects of Obelisks on human health, whether harmful or beneficial, are still unknown. Researchers have detected them in both sick and healthy individuals, meaning they "did not seem to be correlated with any disease." The high accumulation of RNA genomes inside bacteria suggests a possible role in regulating cellular activity with significant implications for health. "These molecules behave in a way different from anything we know so far. We have tried to understand how they interact within their host, with the bacterium Streptococcus sanguinis in the laboratory, but we really don't know what they are doing," said María José López Galiano, a co-author of the work from the University of Valencia.
Obelisks resemble viroids, a family of subviral agents that infect plants. Viroids are even smaller than Obelisks, with about 300 or 400 nucleotides, and are short, single-stranded circular RNA molecules that lack protein-coding capacity. Viroids were shown to infect plants, and Marcos de la Peña commented, "We know that viroids infect plants, but there are also some agents very similar to viroids, like the human hepatitis D virus and other similar RNAs, that infect animals."
The discovery of Obelisks raises fundamental questions about the origin and evolution of viruses and microbial diversity. Marcos de la Peña recalls the RNA world hypothesis, which proposes that these versatile molecules functioned as the first hereditary genetic information in primitive organisms. He explains, "Structurally, they look like they are one of the oldest elements on the planet. They possess all the classic characteristics of what would be the primordial RNA world. These creatures have all the chances of having been there from the beginning."
Despite the significance of this discovery, Marcos de la Peña states that the State Research Agency, dependent on the Ministry of Science, has just rejected funding him a project to continue investigating this enigmatic new world of RNA. He laments, "Doing first-level science in Spain is tremendously complicated. It seems that only scoring a goal in the Second or Third division counts, and winning in the Champions League after assembling top teams is worth nothing." De la Peña states that next year he will have zero euros to research.
Future studies are needed to uncover the possible impact and role of these RNAs. "Now we have to see how they function at the molecular level and how they replicate," said Marcos de la Peña. The discovery shows that the microbial world is much more complex than we imagined. Obelisks are minimal biological entities never before seen that challenge the understanding of the limits of life. "We have opened a door to a whole new field of exploration that may revolutionize our understanding of Virology, Biology, and even the very origin of life on Earth," stated Marcos de la Peña.
Andrew Fire, a biologist at Stanford University who won the Nobel Prize in Medicine in 2006 for demonstrating that small RNA molecules can inactivate specific genes, is among the co-authors of this study. The researchers emphasize that they do not know the hosts of the other obelisks but assume that other bacteria will also harbor these mysterious elements. The discovery of obelisks opens new questions about their definition, potential as infectious agents, effects on humans, and possible applications in medicine, as well as the origin and evolution of microbial diversity.
Obelisks were found in natural ecosystems such as soils, rivers, and oceans, as well as in wastewater and animal microbiomes. Up to 30,000 new species of obelisks have been detected in environmental samples of all types. The researchers have detected nearly 30,000 species of obelisks in biological samples collected worldwide, but only one has been associated with the bacterium Streptococcus sanguinis. "This discovery shows that the microbial world is much more complex than we imagined," said Marcos de la Peña.
Sources: EL PAÍS, Agencia Sinc, Nature, Panamá América, Última Hora, El Nuevo Día
This article was written in collaboration with generative AI company Alchemiq