Analysis of Evolutionarily Independent Protein-RNA Complexes Yields a Criterion to Evaluate the Relevance of Prebiotic Scenarios

A central difficulty facing study of the origin of life on Earth is evaluating the relevance of different proposed prebiotic scenarios. Perhaps the most established feature of the origin of life was the progression through an RNA World, a prebiotic stage dominated by functional RNA. We use the appearance of proteins in the RNA World to understand the prebiotic milieu and develop a criterion to evaluate proposed synthetic scenarios. Current consensus suggests that the earliest amino acids of the genetic code were anionic or small hydrophobic or polar amino acids. However, the ability to interact with the RNA World would have been a crucial feature of early proteins. To determine which amino acids would be important for the RNA World, we analyze non-biological protein-aptamer complexes in which the RNA or DNA is the result of in vitro evolution. This approach avoids confounding effects of biological context and evolutionary history. We use bioinformatic analysis and molecular dynamics simulations to characterize these complexes. We find that positively charged and aromatic amino acids are over-represented whereas small hydrophobic amino acids are under-represented. Binding enthalpy is found to be primarily electrostatic, with positively charged amino acids contributing cooperatively to binding enthalpy. Arginine dominates all modes of interaction at the interface. These results suggest that proposed prebiotic syntheses must be compatible with cationic amino acids, particularly arginine or a biophysically similar amino acid, in order to be relevant to the invention of protein by the RNA World.