Researchers at the University of Tokyo have uncovered a groundbreaking discovery within the human mouth: giant DNA elements known as Inocles. These previously undetected components appear to play a crucial role in helping oral bacteria adapt to the ever-changing environment of the mouth. This revelation provides fresh insights into how oral bacteria colonize and persist in humans, potentially impacting health, disease, and microbiome research.
The discovery of Inocles challenges the assumption that modern medical science has fully mapped the human body. In recent years, the field of microbiome research has experienced a renaissance, shedding light on lesser-known areas such as the oral microbiome. Inspired by recent findings of extraneous DNA in soil microbiomes, Project Research Associate Yuya Kiguchi and his team turned their focus to a collection of saliva samples from the Yutaka Suzuki Lab at the University of Tokyo. Their aim was to uncover similar DNA elements in human saliva.
Unveiling the Hidden DNA
“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,” said Kiguchi. “By exploring this, we discovered Inocles, an example of extrachromosomal DNA — chunks of DNA that exist in cells, in this case bacteria, but outside their main DNA. It’s like finding a book with extra footnotes stapled to it, and we’re just starting to read them to find out what they do.”
Detecting Inocles was no simple task. Conventional sequencing methods often fragment genetic data, making it impossible to reconstruct large elements. To overcome this challenge, the team employed advanced long-read sequencing techniques capable of capturing much longer DNA sequences. A pivotal breakthrough came from co-first author Nagisa Hamamoto, who developed a method called preNuc to selectively remove human DNA from saliva samples, significantly enhancing the quality of sequencing long sections of other DNA.
The Significance of Inocles
For the first time, researchers were able to assemble complete Inocle genomes, which were found to be hosted by the bacteria Streptococcus salivarius. Identifying the host itself posed a significant challenge, but the findings revealed that the average genome size of Inocles is 350 kilobase pairs, making it one of the largest extrachromosomal genetic elements in the human microbiome.
“Plasmids, other forms of extrachromosomal DNA, are at most a few tens of kilobase pairs,” said Kiguchi. “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.”
Future Research and Implications
The research team aims to develop stable methods for culturing Inocle-containing bacteria. This will allow them to investigate how Inocles function, whether they can spread between individuals, and how they might influence oral health conditions such as cavities and gum disease. Many Inocle genes remain uncharacterized, prompting researchers to use a combination of laboratory experiments and computational simulations, such as AlphaFold, to predict and model the roles Inocles may play.
“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,” Kiguchi noted. “Even though the oral microbiome has long been studied, Inocles remained hidden all this time because of technological limitations. 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. There’s even some hints that Inocles might serve as markers for serious diseases like cancer.”
Broader Implications
This discovery opens new avenues for understanding the complex interactions within the human microbiome. As researchers continue to explore the potential roles of Inocles, the findings could lead to significant advancements in oral health and disease prevention. The ability to identify and characterize these giant DNA elements may also offer novel insights into the diagnosis and treatment of serious diseases, potentially transforming approaches to healthcare and personalized medicine.
The research into Inocles is still in its early stages, but the implications for microbiome research and human health are profound. As scientists delve deeper into the mysteries of these giant DNA elements, the potential for groundbreaking discoveries continues to grow, promising to reshape our understanding of the human body’s intricate ecosystems.
