[biorxiv.org] Emergence and evolution of functional RNA and protein structures are the central problems for understanding the origin of life.
Although it is well known that catalytically active RNA elements, ribozymes, can catalyze many reactions, including peptide bond formation, the specifics of the transition from the hypothetical, primordial RNA world to protein-based life centered at the translation system remain enigmatic.
We developed AMES, Atomistic Molecular Evolution Simulator, and employed it to perform computer simulations of the evolution of short RNA molecules and RNA-peptide complexes. Comparison of the evolutionary trajectories and the structures of RNA molecules and RNA-peptide complexes emerging in these simulations shows that short random peptides accelerate RNA evolution, stabilize RNA folds, and boost the structural diversity of evolving RNA molecules, potentially enabling a broader range of activities.
We hypothesize that the RNA world was, actually, an RNA-peptide world, in which, from the earliest stages of evolution, evolving RNA molecules interacted with short random peptides synthesized in a non-templated manner. These interactions could drive the evolution of diverse RNA structures and activities, and eventually, of the translation machinery.
Stability of RNA folds in the presence and in the absence of peptides. A) An example of RNA peptide evolution dynamics. The plot shows the fitness scores for all mutations throughout the simulation (gray dots), for the mutations with the highest score in each generation (blue line) and for the lineage of fixed mutations (purple line). Structures around the plot show intermediate states with arrows pointing to the specific generation in which that intermediate state was detected. Superimposed structures starting from the 300th generation in the lineage are presented on the right. The structures are colored by the pLDDT scores. B) RMSD for RNA and for the peptides, measured after aligning RNA structures, with the thick line showing the mean and the thin transparent lines in the background showing individual simulations. The blue line on the second y-axis, illustrating the mean fitness score of RNA-peptide evolution is shown for comparison with RMSD. C) Final structures from the RNA-peptide simulations. Only RNA270 peptides interaction regions are visualized D) ipTM score reflecting interaction of RNAs evolved in the presence and in the absence of peptides with a new set of random peptides. Split violin plot shows ipTM score distributions for each RNA set. E) Distribution of binding free energies calculated with MMGBSA method. F) Minimum Free Energy (MFE) distribution calculated from secondary structures representing the most thermodynamically stable configuration. G) pTM score distributions for RNA evolved in isolation, RNA-peptide complexes, and RNA from RNA peptide complexes predicted without the peptide (denoted as RNA-peptide*, See Table 2 for statistics). — biorxiv.org
Computational modeling of an RNA-peptide world, biorxiv.org
Astrobiology,
