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Though they are a mystery, once solved, Obelisks could lead to new biomarkers for clinical laboratory testing

Microbiologists and clinical laboratories know that human microbiota play many important roles in the body. Now, scientists from Stanford University have discovered an entirely new class of “viroid-like” lifeforms residing inside the human body. The researchers detected their presence in both the gut microbiome and saliva samples. Most interesting of all, the researchers are not sure what the lifeforms actually are.

The Stanford researchers, led by PhD student Ivan Zheludev, called the new discovery “Obelisks” due to their RNA structures, which are short and can fold into structures that resemble rods.

The scientists believe the Obelisks went undetected until now in the human microbiome due to their compact genetic elements, which are only around 1,000 characters or nucleotides in size. A typical human DNA structure consists of around three billion nucleotides. 

In an article they published on the biology preprint server bioRxiv titled, “Viroid-like Colonists of Human Microbiomes,” the Stanford researchers wrote, “Here, we describe the ‘Obelisks,’ a previously unrecognized class of viroid-like elements that we first identified in human gut metatranscriptomic data. … Obelisks comprise a class of diverse RNAs that have colonized and gone unnoticed in human and global microbiomes.”

The researchers discovered that Obelisks “form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents.”

This is yet another example of how researchers are digging deeper into human biology and finding things never before identified or isolated.

“I am really impressed by the approach. The authors were really creative,” computational biologist Simon Roux, PhD (above) of the Department of Energy (DEO) Joint Genome Institute at Lawrence Berkeley National Laboratory told Science in response to the Stanford researcher’s published findings. “I think this [work] is one more clear indication that we are still exploring the frontiers of this viral universe. This is one of the most exciting parts of being in this field right now. We can see the picture of the long-term evolution of viruses on Earth start to slowly emerge.” How these findings might eventually spark new biomarkers for clinical laboratory testing remains to be seen. (Photo copyright: Berkeley Lab.)

Researchers Bewildered by Obelisks

In their study, “Zheludev and team searched 5.4 million datasets of published genetic sequences and identified almost 30,000 different Obelisks. They appeared in about 10% of the human microbiomes the team examined,” Science reported.

The Stanford researchers found that various types of Obelisks seem to inhabit different areas of the body. In one dataset, the Obelisks were found in half of the oral samples.

The function of Obelisks is unknown, but their discovery is bewildering experts.

“It’s insane,” Mark Peifer, PhD, Michael Hooker Distinguished Professor of Biology at the University of North Carolina School of Medicine told Science. “The more we look, the more crazy things we see.”

According to the bioRxiv paper, the Obelisks share several properties, including:

  • Apparently Circular RNA ~1kb genome assemblies,
  • Rod-like secondary structures encompassing the entire genome, and
  • Open reading frames coding for a novel protein superfamily, which the researchers dubbed “Oblins.” 

At least half of the genetic material of the Obelisks was taken up by these Oblins. The researchers suspect those proteins may be involved in the replication process of the newly-discovered lifeforms.

The Oblins are also significantly larger than other genetic molecules that live inside cells and they do not have the genes to create protein shells that RNA viruses live within when they are outside of cells. 

“Obelisks, therefore, need some kind of host. The researchers managed to identify one: A bacterium called Streptococcus sanguinis that lives mostly in dental plaque in our mouths. Exactly which other hosts obelisks inhabit is yet another mystery, as are what they do to their host and how they spread,” Vice reported.

“While we don’t know the ‘hosts’ of other Obelisks, it is reasonable to assume that at least a fraction may be present in bacteria,” the researchers noted in their bioRxiv paper.

Researchers are Stumped

The Stanford scientists were unable to identify any impact the Obelisks were having on their bacterial hosts—either negative or positive—or determine how they could spread between cells.

“These elements might not even be ‘viral’ in nature and might more closely resemble ‘RNA plasmids,’” they concluded in their paper. 

The Stanford scientists are uncertain as to where or what the hosts of the Obelisks are, but they suspect that at least some of them are present in bacteria. However, Obelisks do not appear to be similar to any biological agents that could provide a link between genetic molecules and viruses. 

And so, Obelisks are a true mystery—one the Stanford researchers may one day solve. If they do, new biomarkers for clinical laboratory testing may not be far behind.

—JP Schlingman

Related Information:

“It’s Insane”: New Virus-like Entities Found in Human Gut Microbes

Viroid-like Colonists of Human Microbiomes

‘Obelisks’: Entirely New Class of Life Has Been Found in the Human Digestive System

Scientists Discover New Lifeform Inside Human Bodies

Scientists Have Identified an Entirely New Form of Life in the Gut: Obelisks

Intriguing Find. Stanford University Discovers Obelisks Hiding in Human Microbiomes

New Lifeform Discovered Inside Human Guts

Scientists Discovered Strange ‘Entities’ Called ‘Obelisks’ in Our Bodies. Their Purpose Is a Mystery.

Obelisks: New Life Found in the Human Digestive System

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