Stone Age bacterial genomes reconstructed to make long-lost molecules

Scientists have reconstructed the genomes of microbes from the Stone Age, and used them to produce new molecules. The complex puzzle was pieced together from DNA fragments of bacteria on the teeth of ancient humans and Neanderthals.

Using tools very similar to those in a modern dentist’s office, the team scraped calcified dental plaque, or tartar, off the teeth of 12 Neanderthal specimens and 34 human specimens, dating back as far as 100,000 years. Within that material are the fossilized remains of ancient bacteria, along with preserved genetic material, but unfortunately it’s far from complete.

“A typical bacterial genome is three million base pairs long, but time fragments the ancient DNA we recover to an average length of only about 30 to 50 base pairs,” said Christina Warinner, senior author of the study. “In other words, each ancient bacterial genome is like a 60,000-piece jigsaw puzzle, and each piece of tooth tartar contains millions of genomes.”

To tackle this impossible puzzle, the researchers tweaked a technique called de novo assembly, which works by looking for fragments that overlap and using that to build up larger and larger sections of a genome. The team optimized the method to work on ultrashort DNA fragments, and were able to reconstruct a few hundred genomes of mostly oral bacteria.

“In addition to the usual suspects, we were also able to reconstruct some genomes that weren’t known before,” said Warinner. “So, this has led to the discovery of new oral species.”

Of these genomes, two in particular stood out for their quality and because they included gene clusters that encode enzymes that produce chemicals. These molecules can potentially be used to make new drugs, fuels, materials and other useful products.

The team created a synthetic version of one of these gene clusters and inserted it into a modern bacteria species. Sure enough the bugs began producing new chemical compounds, which the team named paleofuran A and B, which helped them digest nutrients.

“This is a confirmation that our assemblies are correct, because if there were errors, it would not have worked at all,” said Warriner.

The researchers are currently working on scaling up the technique to handle more data, and speeding up the processes of identifying chemical-producing gene clusters. Ultimately, it might help scientists pull important new molecules from the distant past.

The research was published in the journal Science.

Sources: Harvard

Scientists have reconstructed the genomes of microbes from the Stone Age, and used them to produce new molecules. The complex puzzle was pieced together from DNA fragments of bacteria on the teeth of ancient humans and Neanderthals.

Using tools very similar to those in a modern dentist’s office, the team scraped calcified dental plaque, or tartar, off the teeth of 12 Neanderthal specimens and 34 human specimens, dating back as far as 100,000 years. Within that material are the fossilized remains of ancient bacteria, along with preserved genetic material, but unfortunately it’s far from complete.

“A typical bacterial genome is three million base pairs long, but time fragments the ancient DNA we recover to an average length of only about 30 to 50 base pairs,” said Christina Warinner, senior author of the study. “In other words, each ancient bacterial genome is like a 60,000-piece jigsaw puzzle, and each piece of tooth tartar contains millions of genomes.”

To tackle this impossible puzzle, the researchers tweaked a technique called de novo assembly, which works by looking for fragments that overlap and using that to build up larger and larger sections of a genome. The team optimized the method to work on ultrashort DNA fragments, and were able to reconstruct a few hundred genomes of mostly oral bacteria.

“In addition to the usual suspects, we were also able to reconstruct some genomes that weren’t known before,” said Warinner. “So, this has led to the discovery of new oral species.”

Werner Siemens Foundation, Felix Wey

Of these genomes, two in particular stood out for their quality and because they included gene clusters that encode enzymes that produce chemicals. These molecules can potentially be used to make new drugs, fuels, materials and other useful products.

The team created a synthetic version of one of these gene clusters and inserted it into a modern bacteria species. Sure enough the bugs began producing new chemical compounds, which the team named paleofuran A and B, which helped them digest nutrients.

“This is a confirmation that our assemblies are correct, because if there were errors, it would not have worked at all,” said Warriner.

The researchers are currently working on scaling up the technique to handle more data, and speeding up the processes of identifying chemical-producing gene clusters. Ultimately, it might help scientists pull important new molecules from the distant past.

The research was published in the journal Science.

Sources: Harvard