Discovery of Inocles: Giant DNA Elements in the Human Oral Microbiome

Researchers at the University of Tokyo have identified a previously unknown form of extrachromosomal DNA, termed "Inocles," within the human oral microbiome. These giant DNA elements, averaging 350 kilobase pairs in length, are believed to reside in approximately 74% of the global population. The discovery, detailed in the journal *Nature Communications*, highlights the potential role of Inocles in bacterial adaptation and their implications for oral health and disease.

Scientists Discover Giant DNA Hidden Within the Human Mouth

The identification of Inocles was made possible through advanced long-read sequencing techniques, which allow for the capture of extensive DNA sequences without fragmentation. A significant breakthrough came from the development of a preprocessing method called preNuc, which selectively removes human DNA from saliva samples, thereby enriching bacterial DNA. This innovative approach enabled researchers to assemble complete Inocle genomes, primarily hosted by the bacterium *Streptococcus salivarius*.

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Inocles are among the largest known extrachromosomal elements in the human microbiome, surpassing traditional plasmids in size. The genetic content of Inocles includes a variety of stress-resistance genes, such as those involved in oxidative stress defense and DNA repair mechanisms. Approximately 20% of the genes associated with Inocles are linked to cell wall and membrane functions, suggesting a role in enhancing bacterial colonization of oral tissues.

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The discovery of Inocles carries significant implications for understanding oral health. Preliminary analyses indicate that individuals harboring Inocles exhibit increased B cell activity and elevated levels of inflammatory proteins. Notably, a correlation was observed between Inocle prevalence and certain cancers; patients with head and neck cancer showed reduced Inocle presence compared to healthy controls. This suggests that Inocles may serve as potential biomarkers for specific diseases, including gastrointestinal cancers.

Three Out Of Four People Harbor Giant DNA In Their Mouth

While the findings are groundbreaking, the research team acknowledges that many genes within Inocles remain uncharacterized. Future studies aim to establish stable laboratory cultures of Inocle-containing bacteria to further investigate their functions and potential for horizontal gene transfer. Researchers will employ computational modeling, including tools like AlphaFold, to predict the roles of these elusive genes.

Scientists Discover Giant DNA Hidden Within the Human Mouth

Yuya Kiguchi, the first author of the study, remarked, “What’s remarkable is that, given the range of the human population the saliva samples represent, we think 74% of all human beings may possess Inocles. Now that we know they exist, we can begin to explore how they shape the relationship between humans, their resident microbes, and our oral health.” This statement underscores the significance of the discovery in the broader context of microbiome research.

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• “We know there are a lot of different kinds of bacteria in the oral microbiome, but many of their functions and means of carrying out those functions are still unknown,” — Yuya Kiguchi, Project Research Associate, University of Tokyo

Scientists Find a New Kind of Genetic Element in Mouth Microbes

• “This long length endows Inocles with genes for various functions, including resistance to oxidative stress, DNA damage repair and cell wall-related genes, possibly involved in adapting to extracellular stress response.” — Yuya Kiguchi

Three Out Of Four People Harbor Giant DNA In Their Mouth

• “The discovery raises fascinating questions about the evolutionary origins of Inocles, their mechanisms of maintenance and replication, and their precise roles in bacterial physiology.” — Yuya Kiguchi

Scientists Discover Giant DNA Hidden Within the Human Mouth

The identification of Inocles not only enriches our understanding of the oral microbiome but also opens new avenues for research into microbial contributions to human health and disease.

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