Compositional diversity of minimal coacervates in a nucleic acid-peptide world

The early co-evolution of RNA and peptides is at the core of the RNA-peptide world hypothesis. Recent studies suggest that nucleotides and amino acids could have formed and polymerised non-enzymatically under prebiotic conditions, generating short oligonucleotides and peptides capable of non-enzymatic RNA replication and peptide synthesis. However, whether the cooperation between nucleic acids and peptides stems from their co-localisation in primitive compartments is unclear. Here we demonstrate the early and likely inevitable emergence of primitive coacervates via liquid-liquid phase separation of prebiotic heterogeneous mixtures of short non-coded oligonucleotides and peptides. We show that peptide/nucleic acid coacervates are more prone to form than peptide/peptide coacervates, and that peptide/RNA coacervates are remarkably more stable than peptide/DNA coacervates. Atomistic simulations confirm that the more extended and less structured conformation of RNA over DNA enables more contact points with peptides. The more abundant interactions in peptide/RNA coacervates lead to enhanced salt and thermal stability, yet reduced fluidity compared to their DNA counterparts - which are in turn capable to fully preserve RNA secondary structure upon partitioning. Our findings suggest that peptide/oligonucleotide co-localisation via coacervation would have inevitably occurred at an early stage of a more holistic nucleic acid-peptide world scenario. Both RNA and DNA would have thus been required to ensure the emergence of coacervates with balanced stability and fluidity to host non-enzymatic RNA chemistry.