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TEHRAN (ANA)- Researchers have found that nearly three-quarters of the population carry newly identified genetic elements called Inocles, which may influence oral health, immunity, and cancer risk.<\/p>\n
Researchers at the University of Tokyo and collaborators have uncovered a surprising discovery within the human mouth: Inocles, massive DNA\u00a0elements that until now had gone unnoticed. These structures appear to be essential for helping bacteria adjust to the ever-changing oral environment. The findings shed new light on how bacteria establish themselves and survive in the mouth, with possible consequences for human health, disease, and microbiome research, the journal Nature Communications reported.<\/p>\n
It might seem as though modern medicine has already mapped every detail of the human body. Yet in the past decade alone, researchers have identified small, previously unrecognized organs, and one field undergoing a revival of discovery is the study of the microbiome.<\/p>\n
This includes not only the gut microbiome but also the oral microbiome. Drawing inspiration from recent reports of unusual DNA in soil microbiomes, Project Research Associate Yuya Kiguchi and his team examined a large collection of saliva samples gathered by the Yutaka Suzuki Lab at the Graduate School of Frontier Sciences, University of Tokyo. They set out to determine whether similar hidden DNA elements could be found in human saliva.<\/p>\n
\u201cWe 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,\u201d said Kiguchi. \u201cBy exploring this, we discovered Inocles, an example of extrachromosomal DNA \u2014 chunks of DNA that exist in cells, in this case bacteria, but outside their main DNA. It\u2019s like finding a book with extra footnotes stapled to it, and we\u2019re just starting to read them to find out what they do.\u201d<\/p>\n
Identifying Inocles proved challenging because standard sequencing methods break genetic material into fragments, making it impossible to piece together large elements. To address this, the researchers used advanced long-read sequencing technology capable of capturing extended stretches of DNA.<\/p>\n
A major step forward came from co-first author Nagisa Hamamoto, who created a technique called preNuc that selectively removes human DNA from saliva samples, greatly enhancing the\u00a0accuracy\u00a0of sequencing long fragments of other DNA. With this approach, the team was able to assemble complete Inocle genomes for the first time, discovering that they are hosted by the bacterium\u00a0Streptococcus salivarius, although determining the host itself was a complex task.<\/p>\n
\u201cThe average genome size of Inocle is 350 kilobase pairs, a measure of length for genetic sequences, so it is 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,\u201d said Kiguchi. \u201cThis long length endows Inocles with genes for various functions, including resistance to oxidative stress, DNA damage repair, and cell<\/p>\n
The 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. Since many Inocle genes remain uncharacterized, researchers will use a mixture of laboratory experiments and also computational simulations, such as AlphaFold, to predict and model the roles Inocles may play.<\/p>\n
\u201cWhat\u2019s remarkable is that, given the range of the human population the saliva samples represent, we think 74% of all human beings may possess Inocles. And even though the oral microbiome has long been studied, Inocles remained hidden all this time because of technological limitations,\u201d said Kiguchi. \u201cNow that we know they exist, we can begin to explore how they shape the relationship between humans, their resident microbes, and our oral health. And there\u2019s even some hints that Inocles might serve as markers for serious diseases like cancer.\u201d<\/p>\n
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