Viroid-like

The recently identified Obelisk entities exhibit both similarities and differences to what molecular biologists refer to as viroid-like particles.

To fully grasp these new forms, we must first understand the viroid-like particles they relate to.

Let’s begin with viruses, as the term “viroid-like” implies a resemblance to viral particles.

For more information on viruses, you might refer to my previous article titled "Have You Gone Viral?".

In summary, there are two main virus types: those with an RNA genome and those with a DNA genome.

Viruses can be as small as 20–300 nm, necessitating the use of specialized masks (N95) to filter out such tiny particles to prevent inhalation and potential infections from viruses like COVID, Flu, or RSV.

Viroid-like particles were first identified over a decade ago and consist solely of small RNA segments.

Initially, these were only detected in plant cells, classified into two groups based on the structures formed by their RNA, their functionality, their locations within host cells, and their replication mechanisms.

That’s quite technical, but it’s important to be aware of this context.

These viroid-like particles garnered significant attention due to their potential to infect crops and result in substantial agricultural losses, prompting farmers to seek preventive measures.

Obelisks

When was the last time you heard the term "obelisk"?

I can’t recall, but I doubt it was recent. I’m genuinely surprised I even recognized it as a legitimate word, perhaps from my experience with crossword puzzles.

The term originates from Ancient Greek: ????????? (obeliskos), a diminutive of ?????? (obelus), meaning “spit, nail, pointed pillar,” typically referring to a tall, narrow monument tapering to a pyramid-like point at the top.

The Washington Monument in D.C. is one of the most recognized obelisks in the United States.

Now that we understand the shape and architectural context of an obelisk, do these viroid-like particles share that form?

That’s a complicated question. As far as I know, no one has successfully captured an image of these viroid-like obelisks.

However, let’s explore these “creatures” further and discover why Zheludev and colleagues chose this designation and how they encountered these potential life forms.

Their investigation began with a focus on the human gut microbiome. I have previously written several articles about microbiomes; here’s one you might find informative, written nearly three years ago but still relevant.

Zheludev aimed to analyze the human microbiome for viroid-like and other novel genetic elements. They speculated that, amid the diverse life forms present, they might uncover new genetic elements akin to those found in plants.

To achieve this, they developed a bioinformatics screening tool called VNom, designed to identify new viroid-like elements.

What I find particularly intriguing is that instead of collecting microbiome samples and conducting extensive sequencing, they utilized data from a study conducted nearly five years prior.

This earlier study analyzed fecal samples from 104 donors, each providing multiple samples over a year—a substantial dataset!

Using this accessible data, they employed their VNom tool for scanning.

VNom specifically focused on identifying RNA-based elements, not DNA. And they hit the jackpot! They discovered a new type of viroid-like genetic element that had not been identified before—and in abundance!

These RNA molecules, akin to DNA, are composed of chemically linked nucleotides, albeit with slight chemical variations.

Notably, these newly identified molecules shared a consistent nucleotide count—1164—and other common characteristics.

They named them Obelisks. According to their findings:

> Obelisks possess several features: (i) circular RNA genome assemblies of approximately 1 kb, (ii) predicted rod-like secondary structures encompassing the entire genome, and (iii) open reading frames coding for a novel protein superfamily, termed “Oblins.” They form a distinct phylogenetic group with no detectable similarity to known biological agents.

RNA strands often fold and link to create specific three-dimensional structures. Based on the sequences of these molecules and existing knowledge about the 3-D structures of other RNA, Zheludev’s team was able to predict their appearance.

As mentioned, they are strongly anticipated to adopt rod-like RNA secondary structures, as shown in the first image below. The second image illustrates the circular RNA genome of 1164 nucleotides.

The highlighted yellow and green arrows in the image above indicate two proteins encoded by the RNA sequence, named Oblin-1 and Oblin-2.

After identifying these elements in their pilot study, they expanded their research using another scanning tool to probe an additional 5.4 million datasets, uncovering around 30,000 Obelisks!

These were categorized into 15 distinct subtypes based on the number of Oblin proteins encoded and the anticipated secondary structures of these proteins.

Here’s a visual representation from their research.

This leads us to the pressing question: “How do they reproduce?”

Obelisk Reproduction

Similar to viruses, viroid-like particles need a host to replicate.

Recall that the initial viroid-like entities were found in association with plants. So, what organisms host and facilitate the reproduction of these elements?

Interestingly, they were not using plant cells for reproduction but were hosted by a pathogenic fungus called Botryosphaeria dothidea.

> [B. dothidea] is a significant phytopathogenic fungus found globally, infecting numerous plant species, including apple, pear, and grape, causing symptoms such as die-back, stem and shoot blight, gummosis, canker, and fruit rot.

For detailed insights, refer to the relevant paper.

Now, regarding our Obelisks, which organisms are they utilizing for reproduction? We know they were isolated from fecal microbiomes, which include bacteria, yeast, fungi, and other viruses.

Zheludev and colleagues faced challenges in pinpointing specific host-agent pairings from metagenomic data. They noted:

> Identifying specific host-agent pairings from metagenomic data presented several challenges. Most samples containing Obelisk homologues retrieved from various searches were derived from complex mixtures like highly biodiverse microbiomes and wastewater samples… Thus, the potential host(s) for Obelisk elements were not immediately clear.

Upon searching for other sequences in the same samples as the Obelisks, they found a correlation with a bacterium, Streptococcus sanguinis (strain SK36), a commensal bacterium in the healthy human oral microbiome.

This is promising, as S. sanguinis is a friendly component of the microbiome, indicating that our Obelisks likely do not pose any pathogenic threats.

Moreover, they stated:

> “…the robust co-occurrence of S. sanguinis SK36 with Obelisk RNA-seq reads… positions S. sanguinis SK36 as a model system for future Obelisk characterization.”

Further research will confirm whether this correlation holds and may uncover additional commensals hosting Obelisks.

Why Call Them Obelisks?

Returning to the nomenclature, Zheludev and colleagues termed these entities "Obelisks" due to the anticipated secondary structure of the RNA strands:

> Given the strong predicted rod-like secondary structure, we refer to this group of RNAs as Obelisk-alpha… At 1164 nt in length, the rod-like structure was striking, as typical mRNA sequences do not readily fold this way (as evidenced by the efforts needed to maximize the degree of “rod-ness” in mRNA vaccines).

Personally, I’m a bit skeptical about this name. A rod-like structure differs from one with a broad base tapering to a narrower point.

It seems they may have taken some liberties with this terminology.

What else could they have called it? I’m currently at a loss for better suggestions, but I’d love to hear your thoughts in the comments!

In Summary

As always, in a publication like this, there is an abundance of detailed and technical information beyond what I can convey in this article. My goal is to highlight critical scientific insights so you can appreciate the significance of these findings.

I highly encourage you to read the original sources if you’re interested in more in-depth information! You’ll undoubtedly learn a lot!

Consider this: they began with a few million data points in their initial investigation using the VNom tool and expanded their search to over 5 million datasets! Incredible!

Such advancements wouldn’t have been feasible just a few years ago! We have made significant strides in our bioinformatics capabilities, and I believe we’re still merely scratching the surface.

Who knows what else remains to be discovered? Additionally, the position of Obelisks within the evolutionary framework of life raises intriguing questions.

Life scientists continuously evaluate and theorize about the origins of life. Obelisks present another example of entities that exhibit some characteristics we associate with life while lacking others.

> Zheludev and colleagues propose that their unusual discovery might not be classified as viruses, but rather an entirely new group of entities bridging the gap between primitive genetic molecules and more complex viruses.

Regardless of your perspective, I find these entities—whatever classification they may belong to—a fascinating demonstration of both our extensive knowledge and the vast unknowns regarding life on Earth.

Until next time,

_Rich_

P.S. If you enjoyed this article, you might also appreciate these posts:

> Exploring Frogs With Transparent Skin: They’re called glass frogs, and you can see their insides right through their skin!

> Unraveling Rafflesia - A Most Unusual Parasitic Plant

> Gigantic Genomes and Supersized Salamander Cells Surprise Scientists and Put a Wrinkle in…

> How Did Amazing Tiny Structures Called Plastids Help Make Plants and People Possible?

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Referenced Sources:

> "‘Obelisks’: Entirely New Class of Life Has Been Found in The Human Digestive System," by Tessa Koumoundouros in Science Alert (Jan 2024)

> "Viroid-like colonists of human microbiomes," by Ivan N. Zheludev, et al., in Biorxiv (Jan 2024)

> "Novel Viroid-Like RNAs Naturally Infect a Filamentous Fungus," by Kaili Dong et al., in Advanced Science (Dec 2022)

> "Viroids: Survivors from the RNA World?" by Ricardo Flores et al., in Annual Review of Microbiology (Sep 2014)

> "Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases," by Jason Lloyd-Price, et al., in Nature (May 2019)