Microbial DNA preserved in the teeth of ancient humans and Neanderthals has been used to reconstruct molecules produced by ancient bacteria. The approach could help us discover new antibiotics or other useful molecules in microbes that may have gone extinct thousands of years ago.
The search for unknown microbes might normally send researchers to tropical islands or hydrothermal vents. Pierre Stallforth at Friedrich Schiller University Jena in Germany and his colleagues went hunting back in time. They looked to the microbial DNA preserved in the calcified tooth plaque from 34 ancient humans and 12 Neanderthals, including one that was 102,000 years old.
The ancient DNA came fragmented in millions of short, often degraded, sequences. Assembling these into sufficiently complete genomes is a “multidimensional jigsaw puzzle”, says Stallforth.
From nine of the specimens, the researchers were able to piece together high-quality genomes of two unknown species of green sulphur bacteria from the genus Chlorobium. The species might be unknown because living specimens hadn’t been sequenced before, or because they are now extinct, according to the researchers.
Chlorobium species aren’t usually part of the oral microbiome, so Stallforth says they suspect the bacteria ended up in the specimens’ mouths via contaminated drinking water.
Many microbial genomes have been at least partially reconstructed from ancient DNA, but the researchers went a step further with these ones. They inserted a cluster of three genes from the Chlorobium genome into living bacteria to synthesise molecules the ancient bacteria would have made.
The researchers dubbed the resulting molecules “paleofurans”. Comparisons of the genes used to make paleofurans to genes in modern Chlorobium suggest the molecules could be involved in regulating photosynthesis in the bacteria, says Stallforth. “We found a simple natural product.”
While the paleofurans aren’t likely to have useful applications themselves, Hendrik Poinar at McMaster University in Canada says they provide proof of concept that ancient microbial diversity can be used to discover new molecules that might be useful as antibiotics or for other purposes.
“A lot of microbial diversity has likely gone extinct or at least been pushed to the back burner due to pressure from antimicrobial resistance,” he says. “So we aren’t seeing today what existed in deeper time.”
But Claudiu Supuran at the University of Florence in Italy is sceptical that going back in time is the best way to discover revolutionary new molecules. “There are so many possibilities of genome mining and engineering strategies for organisms living nowadays.”