Major Breakthrough – Stone Age Molecules Revived By Scientists

Conny Waters - AncientPages.com - Breakthroughs in ancient genome reconstruction and biotechnology are now revealing the rich molecular secrets of Paleolithic microorganisms.

In a new study published in Science, a transdisciplinary team of researchers led by the Leibniz Institute for Natural Product Research and Infection Biology, the Max Planck Institute for Evolutionary Anthropology, and Harvard University reconstructed bacterial genomes of previously unknown bacteria dating to the Pleistocene.

Dental calculus (tooth tartar) preserves DNA over millennia, providing unprecedented information about the biodiversity and functional capabilities of ancient microbes. Credit: Werner Siemens Foundation, Felix Wey

Using their genetic blueprints, they built a biotechnology platform to revive the ancient bacteria's natural products.

Microbes are nature's greatest chemists, and among their creations are a large number of the world's antibiotics and other therapeutic drugs. Producing these complicated chemical natural products is not straightforward, and to do so bacteria rely on specialized kinds of genes that encode enzymatic machinery capable of making such chemicals.

At present, scientific study of microbial natural products is largely limited to living bacteria, but given that bacteria have inhabited the Earth for more than 3 billion years, there is an enormous diversity of past natural products with therapeutic potential that remain unknown to us—until now.

"In this study, we have reached a major milestone in revealing the vast genetic and chemical diversity of our microbial past," says co-senior author Christina Warinner, Associate Professor of Anthropology at Harvard University, Group Leader at the Max Planck Institute for Evolutionary Anthropology (MPI-EVA), and Affiliate Group Leader at the Leibniz Institute of Natural Product Research and Infection Biology (Leibniz-HKI).

"Our aim is to chart a path for the discovery of ancient natural products and to inform their potential future applications," adds co-senior author Pierre Stallforth, Professor of Bioorganic Chemistry and Paleobiotechnology at Friedrich Schiller University Jena and Head of the Department of Paleobiotechnology at the Leibniz-HKI.

A billion-piece jigsaw puzzle

When an organism dies, its DNA rapidly degrades and fragments into a multitude of tiny pieces. Scientists can identify some of these DNA fragments by matching them to databases, but for years microbial archaeologists have struggled with the fact that most ancient DNA cannot be matched to anything known today.

This problem has long vexed scientists, but recent advances in computing are now making it possible to refit the DNA fragments together—much like the pieces of a jigsaw puzzle—in order to reconstruct unknown genes and genomes. The only problem is that it does not work very well on highly degraded and extremely short ancient DNA from the Pleistocene.

"We had to completely rethink our approach," says Alexander Hübner, postdoctoral researcher at the MPI-EVA and co-lead author of the study. Three years of testing and optimization later, Hübner says they reached a breakthrough, achieving stretches of reconstructed DNA more than 100,000 base pairs in length and the recovery of a wide range of ancient genes and genomes. "We can now start with billions of unknown ancient DNA fragments and systematically order them into long-lost bacterial genomes of the Ice Age."