Obelisks: expanding the definition of life
Scientists found a new class of RNA elements called Obelisks living in human microbiomes. They don't match anything we've seen before. The categories of life keep getting blurrier.
The discovery of a novel class of viroid-like RNA elements, termed Obelisks, adds a new chapter to our understanding of biological systems. Found in human microbiomes and across ecological niches on every continent, these RNA elements have characteristics that set them apart from anything previously known.
What are Obelisks?
Obelisks are small, circular RNA molecules with genomes approximately 1,000 nucleotides in length. They have highly structured, rod-like secondary formations and encode proteins from a novel superfamily called Oblins. Unlike viroids or Hepatitis Delta Virus (HDV)-like satellites, Obelisks have no detectable sequence or structural similarity to previously known biological entities. They are a distinct phylogenetic group that went unnoticed in human and environmental microbiomes until now.
These elements were first identified using a bioinformatics tool called VNom, designed to detect viroid-like RNAs in metatranscriptomic datasets. Initial findings revealed their presence in human gut and oral microbiomes: about 7% prevalence in stool samples and 50% in oral samples. Large-scale searches uncovered nearly 30,000 distinct Obelisk sequences from all seven continents.
Expanding the definition of life
Obelisks show how life keeps finding new forms. Viroids, once thought to exist only in plants, turn out to have wider distributions. Obelisks push that boundary further. Their genomes are compact yet functional, encoding proteins with no apparent homology to known sequences. How did such minimalistic genomes evolve? What are the limits of biological information transfer?
Some Obelisks contain hammerhead ribozymes, self-cleaving RNA motifs associated with viroid replication. This suggests certain Obelisks may replicate through rolling-circle replication, a process observed in viroids and HDV. The categories of genetic elements are getting blurrier.
A complex web of relationships
One of the most interesting aspects of Obelisks is their integration into microbial communities. A specific strain of Streptococcus sanguinis, a commensal organism in the human oral microbiome, harbors an Obelisk variant named "Obelisk-S.s." This gives us a glimpse into potential host-agent relationships.
Some Obelisks appear only in gut microbiomes, others mainly in oral microbiomes. This anatomical specificity hints at complex interactions with microbial hosts, interactions that likely affect both microbial ecology and host physiology. Whether Obelisks help or harm their hosts remains unknown.
The illusion of scientific certainty
Scientists sometimes assume we have uncovered all there is to know about fundamental biological processes. Obelisks are a reminder that we have not. Despite decades of research on RNA-based life forms, entire classes of genetic elements have been hiding in plain sight.
The identification of Obelisks required moving away from traditional sequence-matching methods toward molecular-feature-focused approaches. This shift revealed how methodological biases can blind us to novel forms of life. Other undiscovered classes of viroid-like RNAs may exist.
Constructing phylogenetic trees for Obelisks has proven difficult. Classical tools struggle to account for the interplay between RNA secondary structures and protein-coding regions. New computational approaches are needed.
Questions that remain
The discovery of Obelisks raises unanswered questions:
- How do these elements replicate? Do they rely solely on host machinery, or do they have unique mechanisms?
- What roles do Oblin proteins play? Are they involved in RNA binding or other functions?
- How are Obelisks transmitted between hosts? Via virus-like particles or cytoplasmic means?
- What impact do they have on their microbial hosts and on human health?
Implications for future research
The prevalence and diversity of Obelisks suggest they are not curiosities but integral components of microbial ecosystems. Their discovery opens research directions in RNA biology, microbial ecology, and host-microbe interactions:
- Studying Streptococcus sanguinis and Obelisk-S.s could reveal how these elements affect bacterial behavior and human health.
- Investigating anatomical specificity may show how environmental factors shape Obelisk distribution.
- Exploring their potential as mobile genetic elements could illuminate evolutionary processes.
Obelisks are viroid-like RNA elements that don't fit existing categories. They were found by looking differently, not by looking harder. Other unknown classes of life may be waiting for the same treatment.
