As they collect and analyze massive amounts of genetic sequences from plants, animals, and microbes, biologists keep encountering surprises, including some that may challenge the very definition of life. The latest, reported this week in a preprint, is a new kind of viruslike entity that inhabits bacteria dwelling in the human mouth and gut. These “obelisks,” as they’re called by the Stanford University team that unearthed them, have genomes seemingly composed of loops of RNA and sequences belonging to them have been found around the world.

Other scientists are delighted by obelisks’ debut. “It’s insane,” says Mark Peifer, a cell and developmental biologist at the University of North Carolina at Chapel Hill. “The more we look, the more crazy things we see.”

It’s not yet known whether obelisks affect human health, says Matthew Sullivan, an integrative biologist at Ohio State University, but they could alter the genetic activity of their bacterial hosts, which in turn could affect human genes.

Most people know RNA, or ribonucleic acid, as DNA’s alter ego—ferrying proteinmaking recipes encoded in a DNA-based gene to molecular “kitchens” outside the cell nucleus that string together a protein’s amino acids. But more than 200 viruses, including those that cause flu, Ebola, and COVID-19, bypass DNA, having genomes composed only of RNA. Their genomes include sequences encoding the proteins that make up a viral shell and ribozymes, enzymes that let a virus copy its original RNA once inside a cell.

Scientists still debate whether viruses are alive—they can’t replicate independent of a host cell’s molecules—but there are even simpler “creatures.” In the early 20th century, plant pathologists came across viroids, basically an infectious loop of RNA without the typical protein shell of viruses. Viroid genomes don’t encode any proteins at all, it seems. Viroids have drawn a lot of interest because they interact with the genomes of plants, sometimes in devastating ways—they cause stunting and deformation in potatoes, chrysanthemums, and other crops and flowers, for example.

Viroids were long thought to be limited to plants, but there’s been some recent evidence of viroidlike circular RNA genomes amid databases of sequences from animals, bacteria, and other life forms. In a new search for undiscovered RNA genomes, Stanford biologist Andrew Fire, his graduate student Ivan Zheludev, and their colleagues developed sophisticated software to analyze existing catalogs of active genes from microbes that live in humans for RNA sequences predicted to form circles—the structure of the genetic material in both viruses and viroids. “I am really impressed by the approach,” says computational biologist Simon Roux of the DOE Joint Genome Institute at Lawrence Berkeley National Laboratory, who worked on a 2023 paper that hinted bacteria might contain viroids or similar entities. “The authors were really creative.”

The Stanford search yielded nearly 30,000 predicted RNA circles, each consisting of about 1000 bases and likely representing a distinct obelisk. They were unlikely to be bona fide viruses, the team concluded, because RNA viruses typically have many more bases. But some of the obelisk sequences encoded proteins involved in RNA replication, making them more complex than standard viroids. Like viroids, however, obelisks don’t seem to encode proteins that make up a shell. Roux says further work is needed to see how distinct obelisks are from viroids and other viroidlike particles.

Among the human microbial databases examined, obelisk sequences were found in 7% of human gut bacteria and in half the bacteria in the human mouth. And the obelisks in microbes from different parts of the body have distinctive sequences, Fire and colleagues report in their preprint, which was posted on 21 January on bioRxiv. Because obelisks contain genes that are unlike any discovered so far in other organisms, they “comprise a class of diverse RNAs that have colonized, and gone unnoticed in, human, and global microbiomes,” the team writes. (Fire and other co-authors on the preprint declined to comment on their work.)

“I think this [work] is one more clear indication that we are still exploring the frontiers of this viral universe,” says Roux, who is also searching for new kinds of viruslike entities and has helped compile a database of more than 15 million relevant sequences.

One big question is whether viruses evolved from increasingly complex viroids and obelisks, or emerged first and then degenerated into these simpler structures. “This is one of the most exciting parts of being in this field right now,” Roux says: “We can see the picture of the long-term evolution of viruses on Earth start to slowly emerge.”