A Cell So Minimal That It Challenges Definitions of Life

“The diversity of archaea and bacteria that appear to belong to these supergroups of parasitic organisms is very, very large,” he said. He suggested that for bacteria, this could be between 25% and 50% of the total share of species in the group.

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

an extraordinary discovery

Nakayama has built a scientific career by generally observing things more closely than other researchers. He contemplates the already small cell and wonders: Are there even smaller cells that make homes there?

“difference of [in size between parasitic and host cells] “Sometimes this can happen between humans and Godzilla,” Nakayama said. He is fascinated by the potentially vast amount of undiscovered biodiversity that exists in these relationships, and his laboratory looks for such relationships in seawater. The ocean is a nutrient-poor environment that encourages cells to form business partnerships. Sometimes they swim together, loosely bound, exchanging scarce nutrients and energy. At other times their arrangements are more organized.

cytharistes regius Is a globally widespread single-celled dinoflagellate that has a walled, sac-like outer chamber to house symbiotic cyanobacteria. Nakayama and his team discovered the algae by removing seawater samples from the Pacific Ocean using a fine-mesh net. A common technique is to sequence whatever DNA can be found in such a sample soup, an approach called metagenomics.

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

After researchers confirmed they returned to shore at the Tsukuba Laboratory C. regiusThey sequenced every genome associated with that one cell. As expected, they found DNA from its symbiotic cyanobacteria, but they also found something else: sequences that belonged 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 small: only 238,000 base pairs from 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 contain 1.9 million base pairs.) Previously, the smallest known archaeal genome belonged to? Nanoarchaeum equitans – At 490,000 base pairs, it is more than twice as long as the new one found by researchers. They initially thought that this small genome – too large to be mere statistical noise – was a condensed fragment of a much larger genome, accidentally compiled by their software.

“At first, we suspected it might be an artifact of the genome-assembly process,” Nakayama recalled. To investigate, the team sequenced the genome using a variety of techniques and ran the data through several computer programs that assemble fragments of DNA sequences into a complete genome. The different approaches reconstructed exactly the same 238,000-base-pair circular genome. “This stability reassured us that this is the real, complete genome,” he said.

This meant that Nakayama and his team had a new creature on their hands. He named the microbe candidate Sukunarchium mirabile (hereafter known as Sukunarchium) for its remarkably small genome – after Sukuna-biko-na, a Shinto deity notable for his short stature, as well as a Latin word for “extraordinary”.

half-life spectrum

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

Sukunaarchaeum encodes the bare minimum proteins for its replication, and that’s it. The strangest thing is that its genome lacks any sign of the genes needed to process and make molecules, other than those needed for reproduction. Due to the lack of those metabolic components, the organism must outsource growth and maintenance processes to another cell, a host on which the microbe is completely dependent.

Other symbiotic microbes have destroyed most of their genomes, including evolutionary relatives of Succinarchium. The researchers’ analysis revealed that the microbe is part of the DpaN archaea, sometimes called nanoarchaea or ultra-small archaea, which are characterized by small size and small genomes. DPANN archaea are generally thought to be symbiotic that cling to the outside of larger prokaryotic microbes, and many of them have substantially reduced genomes to match that lifestyle. But until now, none of the DPANN species had such short genomes. And Succulunarchium diverged early from the DpanN lineage, suggesting that it had begun its own evolutionary journey.

,This area of ​​archaea is in general quite mysterious,, said Brett Baker, a microbial ecologist at the University of Texas at Austin who was not involved in the work. ,[DPANN archaea are] Apparently their metabolic capabilities are limited.

While Succinarchium may provide some undetermined benefits to its host—which may C. regiusSymbiotic cyanobacteria or another cell entirely – it is probably a self-absorbed parasite. “Its genome reduction is entirely driven by 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 the succinarchium and any other cell would probably be one-way.

Other microorganisms have evolved in similarly extreme, well-organized forms. For example, bacteria carsonella ruddiwhich lives as a symbiont in the guts of nectar-feeding insects, has an even smaller genome than Succinarchium, at about 159,000 base pairs. However, these and other ultra-small bacteria do have metabolic genes to produce nutrients such as amino acids and vitamins for their hosts. Instead, their genome has eliminated their ability to reproduce on their own.

“They are on their way to becoming organelles. This is how mitochondria and chloroplasts are thought to have evolved,” Williams said. “But Succunarchium has gone in the opposite direction: the genome retains the genes necessary for its own proliferation, but loses most, if not all, of its metabolic genes.”



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