História natural das aminoacil-tRNA sintetase de classe I e seu papel no estabelecimento do código genético

Abstract

The genetic code is the language whose data stored in the DNA can be translated into proteins. The relation between this stored data in the DNA and the genetic code is held by the machinery of translation, which is responsible for the identification of the codons and the association with its respective amino acid. Among the proteins involved in the translation, it is possible to highlight the aminoacyl-tRNA synthetase (aaRS), the enzymes responsible for the association of each amino acid with its respective tRNA. AaRS comprise 20 highly conserved proteins, symmetrically divided between two classes: class I (ArgRS, CysRS, GlnRS, GluRS, IleRS, LeuRS, MetRS, TrpRS, TyrRS, ValRS) and class II (AlaRS, AsnRS, AspRS, GlyRS, HisRS, LysRS, PheRS, ProRS, SerRS, ThrRS). For a better comprehension of the genetic code establishment, several analyzes are necessary regarding the translation machinery component evolution, since all of them are related. Thus, this paper proposes to analyze the class I aaRS molecular evolution, the role played by the tRNA and the implication of these events over the genetic code establishment. For the mentioned analysis, ancestral sequences for 9 aaRS of class I were generated, and later these sequences were modeled. Molecular docking studies between ancestral structures modeled with the anticodon loop and the cognate tRNA acceptor arm of each aaRS were conducted. Our results indicate the progressive evolution of the aaRS structures, with the acquisition of some domains, such as the domain responsible for the amino acid revision, and the peptide-binding domain (CP). It is hypothesized that the acquisition of these structures started from gene duplication events, horizontal gene transfer and domain exchange and merger mechanism. Besides that, tRNA structures show preference for the aaRS catalytic region when linked to ancestral structures, generating the belief that this region was the first to arise in the aaRS. At a first moment, this link between the tRNA and aaRS was firm, acting on the stability of proteins, and has been decreased over time. This decrease in bond strength can be a reflection of the plasticity acquired by the two structures, since both were acquiring complexity, being subsequently co-opted to load information. This way, it is possible to outline a model in which the tRNA and the aaRS can mutually stabilize as they acquire complexity, being subsequently co-opted from a structure function to an informational function.