Giant loops of DNA carried by bacteria in our mouth may have a beneficial impact on our oral health and our immune systems, potentially reducing the risk of certain cancers.
Named ‘Inocles’, the recently discovered rings of nucleic acid appear to be a large type of plasmid; genetic elements found outside of the main DNA instruction manual in many microbes.
A team led by researchers from the University of Tokyo says Inocles are likely to play an important role in helping bacteria – in this case, Streptococcus bacteria – adapt to the biological environment in the mouth, like bonus survival kits.
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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,” says University of Tokyo microbiologist Yuya 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.”
The giant DNA loops were discovered through a careful study of saliva samples from 56 volunteers, with further tests conducted on 476 samples to determine the prevalence of Inocles in the general population. Around three-quarters of us could be carrying the elements, the data shows.
Ironically, one reason Inocles hadn’t been spotted before could come down to its extraordinary size. Conventional DNA sequencing techniques involve chopping the DNA up into smaller fragments, which, though easier to read, makes the reconstruction of larger sequences more challenging.
To get around this problem, the researchers invented a bespoke sequencing system called preNuc, which removed human DNA from the sample, reducing the number of bacterial DNA jigsaw-pieces to sift through.
“The average genome size of [an] 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,” says Kiguchi. “Plasmids, other forms of extrachromosomal DNA, are at most a few tens of kilobase pairs.”
“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.”
Surprisingly, people with head and neck cancer among the larger group of saliva samples had far fewer of these DNA elements in their mouths, hinting at a potential benefit bestowed by the loops. Whether Inocles could be protecting against cancer, or whether some other factor might be reducing the number of Inocles while raising the risk of cancer, is yet to be determined.
The researchers are also keen to look at how the genes in Inocles might function, whether or not they can spread between people, and what sorts of impacts they could have on oral health.
“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,” says Kiguchi.
The research has been published in Nature Communications.
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