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.
Highlights
Aminoacyl-tRNA synthetases are multidomain protein enzymes that attach L-amino acids to their cognate tRNAs with high specificity [1]
The resulting aminoacyl-tRNAs are the substrates of ribosomal protein synthesis. aaRSs define the algorithmic rules of the genetic code in a two-step reaction that correctly pairs amino acids with tRNA isoacceptors and overcomes an enzymatic step that is,107 slower than peptide bond formation
We show that dipeptides of protein domains appearing in evolution before the first anticodon-binding domain are significantly enriched in amino acids that are subject to aaRS editing
Summary
Aminoacyl-tRNA synthetases (aaRSs) are multidomain protein enzymes that attach L-amino acids to their cognate tRNAs with high specificity [1]. The catalytic aminoacylation domain of the enzyme contains an amino acid binding site capable of activating a specific amino acid by condensation with ATP to form aminoacyladenylate. This activated molecule esterifies the 29 or 39hydroxyl group of the ribose in the 39 end of the acceptor arm of tRNA. The aminoacylation site rejects larger amino acids and an editing site (in an editing domain present in about half of aaRSs) generally hydrolyzes those small amino acids that were incorrectly activated. Little is known about the origin and history of accretion of the domains that provide the crucial aminoacylation, editing and anticodon-binding specificities, and much less about the emergence of the genetic code
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
