title: Structural phylogenomics retrodicts the origin of the genetic code and uncovers the evolutionary impact of protein flexibility.
abstract: The genetic code shapes the genetic repository. Its origin has puzzled molecular scientists for over half a century and remains a long-standing mystery. Here we show that the origin of the genetic code is tightly coupled to the history of aminoacyl-tRNA synthetase enzymes and their interactions with tRNA. A timeline of evolutionary appearance of protein domain families derived from a structural census in hundreds of genomes reveals the early emergence of the 'operational' RNA code and the late implementation of the standard genetic code. The emergence of codon specificities and amino acid charging involved tight coevolution of aminoacyl-tRNA synthetases and tRNA structures as well as episodes of structural recruitment. Remarkably, amino acid and dipeptide compositions of single-domain proteins appearing before the standard code suggest archaic synthetases with structures homologous to catalytic domains of tyrosyl-tRNA and seryl-tRNA synthetases were capable of peptide bond formation and aminoacylation. Results reveal that genetics arose through coevolutionary interactions between polypeptides and nucleic acid cofactors as an exacting mechanism that favored flexibility and folding of the emergent proteins. These enhancements of phenotypic robustness were likely internalized into the emerging genetic system with the early rise of modern protein structure.
authors.affiliation: Evolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Caetano-Anollés
authors.forename: Minglei
authors.initials: M
authors.lastname: Wang
authors.forename: Derek
authors.initials: D
authors.lastname: Caetano-Anollés
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D019143:Evolution, Molecular; D005815:Genetic Code / Q000235:genetics*; D023281:Genomics / Q000379:methods; D008957:Models, Genetic; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D010455:Peptides; D011506:Proteins; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases