Structural Phylogenomics Retrodicts the Origin of the Genetic Code and Uncovers the Evolutionary Impact of Protein Flexibility

摘要: The genetic code shapes the repository. Its origin has puzzled molecular scientists for over half a century and remains long-standing mystery. Here we show that of is tightly coupled to history aminoacyl-tRNA synthetase enzymes their interactions with tRNA. A timeline evolutionary appearance protein domain families derived from structural census in hundreds genomes reveals early emergence ‘operational’ RNA late implementation standard code. codon specificities amino acid charging involved tight coevolution synthetases tRNA structures as well episodes recruitment. Remarkably, dipeptide compositions single-domain proteins appearing before suggest archaic homologous catalytic domains tyrosyl-tRNA seryl-tRNA were capable peptide bond formation aminoacylation. Results reveal genetics arose through coevolutionary between polypeptides nucleic cofactors an exacting mechanism favored flexibility folding emergent proteins. These enhancements phenotypic robustness likely internalized into emerging system rise modern structure.