Co-evolution of RNA and peptides at the dawn of life?

• Applicant: Professor Dr. Dieter Braun
• Subject Area: Biological and Biomimetic Chemistry ; Biochemistry ; Biophysics ; Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560316245

The origin of life on Earth is one of the deepest mysteries of humankind. Only recently have methods become available to study the early evolution of the first molecules. Based on these experiments, we believe that early evolution was a rapid process that can be traced and explained by laboratory experiments with experimental timescales of days and weeks, not millions of years. One of the central mysteries of life is the choice of molecules. Why did nature choose nucleotides and amino acids to evolve the core of biology, creating a co-evolution of RNA and peptides, the two polymers of life? Preliminary experiments suggest a common set of ring-opening polymerisation mechanisms catalysed by both nucleobases and amino acids under alkaline pH in the dry state. As a result, we expect peptides to help 2',3'-cyclic nucleotides form RNA and RNA to help amino acids form peptides. Due to limited energetic activation energies, non-equilibrium conditions are a crucial driving force. These include wet-dry cycling and heat-induced accumulation and pH cycling. These conditions are motivated by volcanic environments. These are probably the only dry places on the early Earth and are known to have alkaline freshwater reservoirs in porous rock environments. We have assembled an international team with expertise in RNA and peptide chemistry and non-equilibrium experiments. We expect to find common conditions for both catalytic effects at alkaline pH, revealing a mutual, not yet discussed co-evolutionary dynamic between RNA and peptides under repeated wet-dry cycles. If positive, we expect increased lengths of both peptides and RNA, as well as the formation of novel peptide-RNA hybrids that will drive the purification of both polymers in terms of homochirality of both peptides and RNA as well as creating a pure replicative 3',5' RNA backbone linkage. The implications of understanding the origin of life are profound and will reshape the first chapters of all biology textbooks, and will impact on related fields such as in vitro evolution, evolutionary chemistry and synthetic biology by creating evolutionary systems using the core molecules of life.

• DFG Programme: Research Grants
• International Connection: Israel
• Partner Organisation: The Israel Science Foundation
• Cooperation Partner: Professorin Dr. Moran Frenkel-Pinter