Which bacteria colonized the oral cavity of our ancestors thousands of years ago? And what chemical natural products did they produce? A new study that reconstructed ancient DNA from the tartar of ancient humans and Neanderthals provides answers to these questions. Among other things, the researchers discovered a previously unknown, extinct type of bacteria. By inserting some genes from primeval bacteria into present-day bacteria, they got them to produce the ancient gene products: a new group of substances called paleofurans. In the future, the method could help to develop new medicines such as antibiotics.
Bacteria produce numerous metabolic products, many of which are useful for us humans. For example, many antibiotics are based on substances that bacteria produce to ward off competitors. For science, the microorganisms are therefore an important source in the search for new drugs. So far, only bacteria that are alive today have been available for this purpose. Even in bacteria that are already extinct, researchers suspect a large variety of potentially therapeutically useful natural substances. One challenge, however, lies in tracking down, isolating and reconstructing the old DNA fragments of microorganisms, which are only preserved in fragments.
Puzzle game with ancient DNA
A team led by Martin Klapper from the Leibniz Institute for Natural Product Research and Infection Biology in Jena has now mastered this challenge. In the tartar of 12 Neanderthals, who lived around 100,000 to 40,000 years ago, and 52 anatomically modern humans, who lived between 30,000 and 150 years ago, the team found tiny fragments of the DNA of primeval microorganisms. In order to assign such DNA fragments and assemble them into genomes that are as complete as possible, researchers usually use reference databases that contain the genetic information of living organisms. However, this approach only helped to a limited extent: On the one hand, the DNA fragments were very small and very badly degraded. On the other hand, they came at least in part from extinct microorganisms whose genome has not yet been recorded in any database.
"The major bioinformatics challenge was to correct errors in the degraded DNA and to rule out contamination, for example by younger DNA," says Klapper's colleague Anan Ibrahim. With the help of new bioinformatic methods, the researchers finally succeeded in reconstructing DNA sections with a length of more than 100,000 base pairs and restoring a large number of old genes and genomes. "We can now begin to systematically classify billions of unknown ancient DNA fragments into long-lost Stone Age bacterial genomes," says co-author Alexander Hübner from the Max Planck Institute for Evolutionary Anthropology in Leipzig.
New group of substances from primeval bacteria
In the reconstructed genomes, the team found the genetic traces of numerous microorganisms that are still part of our oral flora today. On the other hand, they discovered a previously unknown type of bacteria of the genus Chlorobium in the tartar of seven humans and Neanderthals. All seven chlorobium genomes contained a biosynthetic gene cluster - the blueprint for enzymes - with an unknown function. A particularly well-preserved chlorobium genome was reconstructed from the tartar of the approximately 19,000-year-old "Red Lady of El Mirón", Spain. The skeleton found in a Spanish cave in 2010 is the oldest evidence of a Magdalenian burial on the Iberian Peninsula.
"Once we discovered these mysterious ancient genes, we wanted to find out what they do," says Ibrahim. To do this, the research team incorporated the primeval genes into the genome of living bacteria. They then began to produce the corresponding gene products. The result was substances from a previously unknown group of substances, which the researchers gave the name palaeofurans. "This is the first step in unlocking the hidden chemical diversity of microbes throughout Earth's history," says Klapper. In the future, they could use the same technology to produce numerous other gene products from primeval bacteria. "With this study, we have reached an important milestone in uncovering the enormous genetic and chemical diversity of our microbial past," says Hübner's colleague Christina Warinner.
Source: Martin Klapper (Leibniz Institute for Natural Product Research and Infection Biology, Jena) et al., Science, doi: 10.1126/science.adf5300