Obelisks: Expanding the Definition of Life

The discovery of a novel class of viroid-like RNA elements, termed Obelisks, has unveiled a fascinating new dimension of life that challenges our understanding of biological systems. Found within human microbiomes and across diverse ecological niches globally, these RNA elements exhibit unique characteristics that distinguish them from previously known biological agents. This discovery underscores the vast complexity of life and the intricate relationships between species, while also highlighting how much remains to be learned in the field of science.

What are Obelisks?

Obelisks are small, circular RNA molecules with genomes approximately 1,000 nucleotides in length. They are characterized by highly structured, rod-like secondary formations and the ability to encode proteins from a novel superfamily called Oblins. Unlike traditional viroids or Hepatitis Delta Virus (HDV)-like satellites, Obelisks lack detectable sequence or structural similarity to previously known biological entities. This makes them a distinct phylogenetic group that has gone unnoticed in human and environmental microbiomes until now.

These elements were first identified using a bioinformatics tool called VNom, which was specifically designed to detect viroid-like RNAs in metatranscriptomic datasets. Initial findings revealed their presence in human gut and oral microbiomes, with a prevalence of approximately 7% in stool samples and 50% in oral samples. Subsequent large-scale searches uncovered nearly 30,000 distinct Obelisk sequences from all seven continents, suggesting their widespread distribution across diverse ecosystems.

Expanding the Definition of Life

The discovery of Obelisks exemplifies how life continues to surprise us with its ability to coalesce into new forms. Viroids, traditionally thought to be restricted to plants, are now understood to have broader distributions. Similarly, Obelisks expand the boundaries of what we consider viable genetic entities. Their genomes are not only compact but also highly efficient, encoding proteins with no apparent homology to known sequences. This raises fundamental questions about the limits of biological information transfer and the evolutionary pressures that shape such minimalistic yet functional genomes.

Moreover, some Obelisks harbor specific variants of hammerhead ribozymes—self-cleaving RNA motifs commonly associated with viroid replication. These ribozymes suggest that certain Obelisks may replicate through mechanisms akin to rolling-circle replication, a process observed in viroids and HDV. This functional similarity further blurs the lines between established categories of genetic elements.

A Complex Web of Relationships

One of the most intriguing aspects of Obelisks is their apparent integration into microbial communities. For example, a specific strain of the bacterium Streptococcus sanguinis, a commensal organism in the human oral microbiome, was found to harbor an Obelisk variant named "Obelisk-S.s." This association provides a rare glimpse into potential host-agent relationships for these enigmatic elements.

The anatomical specificity of Obelisks—some being restricted to gut microbiomes and others predominantly found in oral microbiomes—hints at complex interactions with their microbial hosts. These interactions likely influence both microbial ecology and host physiology. However, whether Obelisks confer benefits or impose costs on their hosts remains an open question.

This discovery underscores a broader truth: life is not an isolated phenomenon but rather a network of interdependent relationships. The interplay between Obelisks and their microbial hosts exemplifies this interconnectedness, offering new perspectives on how life evolves and adapts within ecosystems.

The Illusion of Scientific Certainty

In science, there is often a tendency to believe that we have uncovered all there is to know about fundamental biological processes. Yet discoveries like Obelisks serve as humbling reminders that our understanding is far from complete. Despite decades of research on RNA-based life forms, entire classes of genetic elements have remained hidden in plain sight.

The identification of Obelisks was made possible by shifting away from traditional sequence-matching methods toward molecular-feature-focused approaches. This paradigm shift highlights how methodological biases can blind us to novel forms of life. It also suggests that other undiscovered classes of viroid-like RNAs may exist, waiting to be revealed through innovative techniques.

Furthermore, constructing phylogenetic trees for Obelisks has proven challenging due to their unique structural constraints and evolutionary signals. Classical tools struggle to account for the interplay between RNA secondary structures and protein-coding regions, underscoring the need for new computational approaches that integrate these complexities.

Questions That Remain

The discovery of Obelisks raises numerous 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 in their lifecycle? Are they involved in RNA binding or other functions?
• How are Obelisks transmitted between hosts? Do they spread via virus-like particles or through cytoplasmic means?
• What impact do they have on their microbial hosts and, by extension, on human health?

These questions highlight the vast gaps in our knowledge about these elements and their broader implications for biology.

Implications for Future Research

The prevalence and diversity of Obelisks suggest that they are not mere curiosities but integral components of microbial ecosystems. Their discovery opens up new avenues for research into RNA biology, microbial ecology, and host-microbe interactions. For example:

• Studying the relationship between Streptococcus sanguinis and Obelisk-S.s could provide insights into how these elements influence bacterial behavior and human health.
• Investigating the anatomical specificity of Obelisks may reveal how environmental factors shape their distribution.
• Exploring their potential roles as mobile genetic elements could shed light on broader evolutionary processes.

Ultimately, the study of Obelisks underscores the importance of curiosity-driven science. By venturing beyond established paradigms and embracing uncertainty, researchers can uncover hidden dimensions of life that challenge our understanding and inspire new questions.

The discovery of Obelisks represents a significant milestone in our quest to understand life's diversity and complexity. These viroid-like RNA elements challenge existing definitions of genetic entities while highlighting the intricate relationships between species within ecosystems. At the same time, they serve as a powerful reminder that science is an ever-evolving journey marked by discovery and humility.

As we continue to explore uncharted territories in biology, it becomes increasingly clear that we are only scratching the surface of what is possible. The story of Obelisks is not just about uncovering a new class of genetic elements; it is about embracing the unknown and recognizing that life's mysteries are far more profound than we can imagine.