Reactivated genes from Stone Age dental plaque reveal stray microbes in the mouth

A reconstruction of the genomes of oral microflora spanning a whopping 100,000 years of human history may have revealed a startling shift in the types of bacteria that like to call our mouths home.

Researchers from across Germany and the US teamed up to decode DNA extracted from dental plaque from human and Neanderthal remains, using the sequences to recreate proteins used by the bacteria.

It’s a huge moment in the study of the microbes that humans harbor, giving us insight into bacteria that are no longer part of our body’s personal ecosystem. In the future, these discoveries could even be used to develop new drug treatments.

Tartar, or calcified dental plaque, is a perfect hiding place for microbes, which is why your dentist emphasizes the importance of brushing and flossing your teeth daily. As good as it is at providing protection for the bacteria, the researchers were still able to extract only small pieces of DNA from the old samples to work with. That left a lot of scientific detective work to decipher the sequences.

“A typical bacterial genome is 3 million base pairs long, but time fragments the ancient DNA we recover to an average length of only 30 to 50 base pairs,” says anthropologist Christina Warinner of Harvard University in Massachusetts.

“In other words, each ancient bacterial genome is like a 60,000-piece jigsaw puzzle, and each piece of dental tartar contains millions of genomes.”

The researchers started with plates from 12 Neanderthals (between 40,000 and 102,000 years old) and 34 humans (between 150 and 30,000 years old).

Previously, such genetic fragments would have been compared to the genomes of modern microbial species – a useful reference, but one that will never reveal new or extinct species.

In this case, the researchers refined a process known as the de novo assembly technique, in which smaller pieces of DNA can be built into an entire genome.

It’s a bit like trying to put together a jigsaw puzzle with just a few pieces and no pictures to work with. A variety of tricks, including identifying overlaps and patterns, are deployed to try and fill in the gaps – and after three years of careful comparison and analysis across all samples, the bacterial genomes could be reconstructed.

From the remarkable quality genomes, the researchers identified a shared sequence called biosynthetic gene clusters. Genes within these groups play an important role in building proteins within the bacteria.

“This is how bacteria make really complicated and useful chemicals,” it says Warinner. “Almost all of our antimicrobials and many of our drug treatments derive from these bacterial biosynthetic gene clusters.”

By transferring reconstructed DNA sequences into modern bacteria, researchers have successfully produced enzymes based on the ancient blueprints of microbes that lived in the mouths of our ancestors. One of these enzymes produced organic molecules known as furans, that are now involved in signaling between bacterial cells.

Based on a study of the genes on both sides of the furan-producing enzyme, the researchers suspect that this specific version may play a role in regulating bacterial photosynthesis.

Altogether, the greatest number of high-quality sequences appeared to belong to a genus of bacteria called chlorobium. Capable of using light to oxidize sulfur for energy, these microbes aren’t exactly the kinds of organisms we’d expect to be nestled against our teeth.

It is possible that they once lived in the human mouth, absorbing the few rays that warm our tonsils whenever we open our mouths. Or they were a consequence of drinking pond water.

While we’re not talking about bringing microbes back to life here – a bacterial version of Jurassic Park – ancient genomes are useful for telling scientists how our microbiome might have changed and evolved over tens of thousands of years.

For example, there is the question of why these bacteria are no longer in our mouths – perhaps due to a change in behavior or drinking habits – something that future research could look into.

“Now we can extend this process”, says Warinner. “Suddenly, we can vastly expand our understanding of the biochemical past.”

The research was published in Science.

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