In an interdisciplinary study, scientists reconstruct 100,000-year-old microbial natural products using tartar from humans and Neanderthals.

Breakthroughs in ancient genome reconstruction and biotechnology are now revealing the rich molecular secrets of Paleolithic microorganisms. In a new study published in Science, an interdisciplinary research team led by the Leibniz Institute for Natural Product Research and Infection Biology, the Max Planck Institute for Evolutionary Anthropology, and Harvard University reconstructed the bacterial genomes of previously unknown bacteria that date back to the Pleistocene. . Using their genetic blueprint, they created a biotechnological platform to recreate the natural products of ancient bacteria.

Microbes are nature’s greatest chemists, and among their creations are the world’s many antibiotics and other therapeutic drugs. These complex chemical natural products are not easy to manufacture, and to do so, bacteria rely on special types of genes that encode the enzymatic machinery that can produce such chemicals. Currently, scientific research on microbial natural products is mostly limited to living bacteria, but given that bacteria have lived on Earth for more than 3 billion years, there is a wide variety of past natural products with therapeutic potential that we do not know until now. .

“In this study, we have reached an important milestone in revealing the enormous genetic and chemical diversity of our microbial history,” says Christina Warinner, one of the senior authors, professor of anthropology at Harvard University and group leader at the Max Planck Institute. for evolution. Head of an affiliated group in anthropology and the Leibniz Institute for Natural Products and Infection Biology (Leibniz-HKI). “Our aim is to chart a path for the discovery of ancient natural products and inform their potential future applications,” adds Pierre Stolfort, professor of bioorganic chemistry and paleobiotechnology at Friedrich Schiller University in Jena and one of the senior authors. paleobiotechnology department. At Leibniz-HKI.

One billion puzzles

When an organism dies, its DNA rapidly degrades and breaks down into many small pieces. Scientists can identify some of these DNA fragments by matching them to databases, but microbial archaeologists have struggled for years with the fact that the oldest DNA cannot be matched to anything known today. This problem has plagued scientists for a long time, but recent advances in computation now allow bits of DNA to be put together like puzzle pieces to reconstruct unknown genes and genomes. The only problem is that it doesn’t work very well on highly degraded and extremely short ancient Pleistocene DNA.

“We had to completely rethink our approach,” says Alexander Hübner, a PhD student at the Max Planck Institute for Evolutionary Anthropology and co-author of the study. After three years of testing and optimization, Hübner says they have made a breakthrough by reaching reconstructed stretches of DNA longer than 100,000 base pairs and recovering a wide variety of old genes and genomes. “We can now start with billions of unknown pieces of ancient DNA and systematically sequence them into the long-lost genomes of Ice Age bacteria.”

Microbial Paleolithic Study

The team focused on reconstructing bacterial genomes from approximately 12 Neanderthals covered with calculus, also known as calculus. 102,000–40,000 years ago 34 archaeological humans ca. 30,000–150 years ago and 18 modern humans. Tartar is the only body part that regularly fossilizes throughout life, turning living plaque into a graveyard of mineralized bacteria. The researchers reconstructed numerous species of oral bacteria, as well as other more exotic species whose genomes had not been previously described.