The Origin and Evolution of Protein Synthesis: A Co-Adaptation Flexible-Rigid Docking Model Based on First-Principles Reasoning

Abstract

Although the "RNA world" hypothesis suggests that RNA played a crucial role in the origin of life [7], the functional framework of RNA in prebiotic protein synthesis and the mechanisms of genetic code formation during the prebiotic period remain poorly understood. Here, using the prebiotic "primordial soup" as a model, we reconstructed the detailed steps that would yield a protein with a stable ordered amino-acid sequence in the "primordial soup" at the prebiotic period. In the "primordial soup", a large number of medium- to large-sized biomolecule-like substances--such as RNA-like and protein-like molecules of various sizes and shapes, as well as related polymers like amino-acid-RNA-like etc.--did generate and accumulate. Moreover, protein-like and RNA-like molecules formed even more intricate complexes. These complexes bound free mRNA-like molecules through complementary base pairing. Subsequently, with an extremely low probability, two adjacent amino-acid-RNA-like molecules became bound to this free mRNA-like molecule, and their amino acids underwent a condensation reaction by the complexes, producing peptides and eventually proteins or polypeptides. This free mRNA-like molecule exhibits a certain flexible structure, whereas the super-large complexes formed by protein-like and RNA-like molecules (which possess certain activities) and the amino-acid-RNA molecules exhibit relatively rigid structures. Long-term evolution and mutual selection led to the emergence of proteins with stable amino acid sequences and moderate catalytic activity. In this way, the nucleotide information embedded in such mRNA-like molecules indirectly express through protein synthesis--a process we term the "A Co-Adaptation Flexible-Rigid Docking Model", where flexible mRNA-like molecules dock onto rigid complexes to enable ordered peptide formation. Finally, we show how trinucleotide codons emerge naturally from the flexible-rigid docking constraints.