Scientists have identified a previously unknown class of RNA entities living inside bacteria that inhabit the human body, challenging long standing definitions of what constitutes life. These structures, called obelisks, do not match any known category of virus, bacterium, or mobile genetic element.
The discovery emerged from large scale analyses of genetic data taken from human associated microbiomes, particularly samples from the mouth and gut. Obelisks appear to be widespread across human populations and have now been detected in thousands of datasets worldwide. Despite their prevalence, their biological role remains unknown, as reported by The Daily Galaxy.
The study used cerebral organoids derived from two human iPSC lines to model the effects of glucocorticoids (GCs). Six treatment conditions were tested in duplicate across four replicates each. Organoids were exposed to either a 10-day chronic GC treatment (100 nM dexamethasone) or a vehicle control (DMSO) starting on day 60, with samples collected at day 70. These day 70 conditions were then cultured for 20 additional days without treatment to generate four day 90 conditions: with or without a 12-hour acute GC exposure. Single-cell RNA-seq and ATAC-seq were performed to examine transcription factor activity and lineage trajectory changes following treatment. Credit: bioRxiv
What makes obelisks unusual is their extreme simplicity. They are short, circular loops of RNA that do not encode proteins and do not appear to form protective shells. Instead, they seem to replicate inside bacterial cells using mechanisms that researchers do not yet understand. This places them outside conventional classifications such as viruses or plasmids.
The research was led by Andrew Fire of Stanford University and published as a preprint on bioRxiv. Using advanced computational screening of public metagenomic data, the team identified more than 3,000 distinct obelisk types. Many were found embedded within bacterial genomes, suggesting long term adaptation to specific microbial hosts.
Structurally, obelisks resemble plant viroids, which are also non coding circular RNAs, but there is a key difference. Viroids infect plants directly, while obelisks appear to exist only within bacteria associated with humans. No direct health effects have been linked to them so far, but their presence in microbes that influence digestion and immunity makes them an important subject for future study.
Beyond microbiology, the discovery has implications for evolutionary biology. Some theories propose that early life on Earth was based on self replicating RNA before proteins and cells evolved. Entities like obelisks may offer a modern glimpse into such primitive biological systems.
Researchers emphasize that this finding highlights how much remains undiscovered within the human microbiome. As sequencing technologies and bioinformatics tools continue to improve, more unclassified forms of genetic life are likely to emerge, potentially reshaping how biology defines the simplest boundaries of living systems.