“The diversity of archaea and bacteria that appear to belong to these supergroups of parasitic organisms is very, very large,” she said. For bacteria, it may be between 25% and 50% of the group’s total share of species, she suggested.

The discovery pushes the boundaries of our knowledge of just how small and simple cellular life can become, as it evolves even into forms that are barely alive.

An Extraordinary Discovery

Nakayama has built a scientific career out of looking more closely than other researchers typically do. He considers an already tiny cell and wonders: Are there even smaller cells that make a home there?

“The difference [in size between parasitic and host cells] can sometimes be like that between a human and Godzilla,” Nakayama said. He is fascinated by the potentially vast amount of undiscovered biodiversity these relationships might contain, and his lab looks for such relationships in seawater. The ocean is a nutrient-poor environment that incentivizes cells to form trading partnerships. Sometimes they float along together, loosely tethered, exchanging rare nutrients and energy. Other times their arrangements are more organized.

Citharistes regius is a globally widespread single-celled dinoflagellate that has a walled, pouchlike external chamber for housing symbiotic cyanobacteria. Nakayama and his team searched for the alga by scooping seawater samples from the Pacific Ocean using a fine-mesh net. A common technique is to sequence whatever DNA can be found in the soup of such a sample, an approach called metagenomics.

“That method is incredibly powerful for capturing a broad overview,” Nakayama said. “However, with such data, it is often difficult to maintain the link between a sequence and the specific cell it came from, and rare organisms can be easily missed.” His team’s more targeted approach involves microscopically identifying and physically isolating a single target cell from that mixed sample.

Back on shore in the Tsukuba lab, after the researchers confirmed they had C. regius, they sequenced every genome associated with that one cell. As expected, they found DNA from its symbiotic cyanobacteria, but they found something else, too: sequences that belong to an archaeon, a member of the domain of life thought to have given rise to eukaryotes like us.

At first, Nakayama and his colleagues thought they had made a mistake. The archaeal genome is tiny: just 238,000 base pairs end to end. In comparison, humans have a few billion base pairs, and even E. coli bacteria work with several million. (C. regius’ symbiotic cyanobacteria have 1.9 million base pairs.) Previously, the smallest known archaeal genome was the one belonging to Nanoarchaeum equitans — at 490,000 base pairs, it is more than twice as long as the new one the researchers found. They initially figured that this tiny genome — too large to be merely statistical noise — was an abbreviated piece of a much larger genome, erroneously compiled by their software.

“At first, we suspected it might be an artifact of the genome-assembly process,” Nakayama recalled. To check, the team sequenced the genome using different technologies and ran the data through multiple computer programs that assemble fragments of DNA sequences into a full genome. The various approaches all reconstructed the exact same 238,000-base-pair circular genome. “This consistency is what convinced us it was the real, complete genome,” he said.

This meant that Nakayama and his team had a new organism on their hands. They named the microbe Candidatus Sukunaarchaeum mirabile (hereafter referred to as Sukunaarchaeum) for its remarkably tiny genome — after Sukuna-biko-na, a Shinto deity notable for his short stature, plus a Latin word for “extraordinary.”

The Spectrum of Quasi-Life

When the team consulted databases of known genes to analyze the archaeon, they found its small size was the result of a whole lot that was missing.

Sukunaarchaeum encodes the barest minimum of proteins for its own replication, and that’s about all. Most strangely, its genome is missing any hints of the genes required to process and build molecules, outside of those needed to reproduce. Lacking those metabolic components, the organism must outsource the processes for growth and maintenance to another cell, a host upon which the microbe is entirely dependent.

Other symbiotic microbes have scrapped much of their genomes, including Sukunaarchaeum’s evolutionary relatives. The researchers’ analysis suggested that the microbe is part of the DPANN archaea, sometimes called nanoarchaea or ultra-small archaea, which are characterized by small size and small genomes. DPANN archaea are generally thought to be symbiotes that cling to the outside of larger prokaryotic microbes, and plenty of them have substantially reduced genomes to match that lifestyle. But until now, none of the DPANN species had genomes quite this pared back. And Sukunaarchaeum branched off the DPANN lineage early, suggesting that it had taken its own evolutionary journey.

“This realm of the archaea is pretty mysterious in general,” said Brett Baker, a microbial ecologist at the University of Texas, Austin who was not involved in the work. “[DPANN archaea are] obviously limited in their metabolic capabilities.”

While Sukunaarchaeum may provide some undetermined benefit for its host — which could be C. regius, the symbiotic cyanobacteria or another cell entirely — it’s probably a self-absorbed parasite. “Its genome reduction is driven by entirely selfish motives, consistent with a parasitic lifestyle,” said Tim Williams, a microbiologist at the University of Technology Sydney who was not involved in the study. It cannot contribute metabolic products, so the relationship between Sukunaarchaeum and any other cell would likely be a one-way street.

Other microbes have evolved similarly extreme, streamlined forms. For instance, the bacterium Carsonella ruddii, which lives as a symbiont within the guts of sap-feeding insects, has an even smaller genome than Sukunaarchaeum, at around 159,000 base pairs. However, these and other super-small bacteria have metabolic genes to produce nutrients, such as amino acids and vitamins, for their hosts. Instead, their genome has cast off much of their ability to reproduce on their own.

“They are on the way to becoming organelles. This is the way mitochondria and chloroplasts are thought to have evolved,” Williams said. “But Sukunaarchaeum has gone in the opposite direction: The genome retains genes required for its own propagation, but lost most, if not all, of its metabolic genes.”