Researchers in Japan have discovered giant DNA elements, called Inocles, living in the human mouth. These structures, found in nearly three-quarters of the population, may influence oral health, immunity, and cancer risk. The team at the University of Tokyo and collaborators announced the discovery of Inocles, massive DNA elements that had gone unnoticed until now.
These structures seem to help bacteria adapt to the ever-changing oral environment, impacting human health, disease, and microbiome research. Despite advancements in modern medicine, the human body still holds many mysteries. Recent studies have led to the identification of small, previously unrecognized organs and renewed interest in microbiome research, including the oral microbiome.
Project Research Associate Yuya Kiguchi and his team examined a large collection of saliva samples from the Yutaka Suzuki Lab at the Graduate School of Frontier Sciences, University of Tokyo. They aimed to determine whether similar hidden DNA elements could be found in human saliva. “We know there are many kinds of bacteria in the oral microbiome, but their functions and mechanisms remain largely unknown,” said Kiguchi.
New DNA discovery in human mouths
“By exploring this, we discovered Inocles, a type of extrachromosomal DNA.”
Identifying Inocles posed a challenge because traditional sequencing methods couldn’t piece together large genetic elements. The researchers used advanced long-read sequencing technology capable of capturing extended DNA stretches.
A significant breakthrough was the preNuc technique, developed by co-first author Nagisa Hamamoto, which selectively removes human DNA from saliva samples, enhancing the sequencing of other DNA. With this approach, the team assembled complete Inocle genomes for the first time, discovering that they are hosted by the bacterium Streptococcus salivarius. The average genome size of Inocle is 350 kilobase pairs, making it one of the largest extrachromosomal genetic elements in the human microbiome.
The team aims to develop stable methods for culturing Inocle-containing bacteria to investigate their functions, transmission between individuals, and influence on oral health issues like cavities and gum disease. Since many Inocle genes remain uncharacterized, researchers will combine laboratory experiments with computational simulations to predict their roles. “What’s remarkable is that, given the range of the human population represented by the saliva samples, we think 74% of all humans may possess Inocles,” Kiguchi said.
“Now that we know they exist, we can explore how they shape the relationship between humans, their resident microbes, and our oral health. There’s even some indication that Inocles might serve as markers for serious diseases like cancer.”
