Laboratório de Genética Evolutiva Paulo Leminsk, Departamento de Biologia Molecular, Universidade Federal da Paraíba, João Pessoa, Brazil.
Laboratório de Genética Evolutiva Paulo Leminsk, Departamento de Biologia Molecular, Universidade Federal da Paraíba, João Pessoa, Brazil.
Prog Biophys Mol Biol. 2019 Mar;142:43-50. doi: 10.1016/j.pbiomolbio.2018.08.007. Epub 2018 Aug 22.
The origin and evolution of the genetic code is a fundamental challenge in modern biology. At the center of this problem is the correct interaction between amino acids and tRNAs. Aminoacyl-tRNA synthetase is the enzyme responsible for the correct binding between amino acids and tRNAs. Among the 20 canonical amino acid, glycine was the most abundant in prebiotic condition and it must have been one of the first to be incorporated into the genetic code. In this work, we derive the ancestral sequence of Glycyl-tRNA synthetase (GlyRS) and predict its 3D-structure. We show, via molecular docking experiments, the capacity of ancestral GlyRS to bind the tRNA anticodon stem loop, cofactors and substrates. These bindings exhibit high affinity and specificity. We propose that the primordial function of these interactions was to stabilize both compounds to make possible the catalysis. In this context, the anticodon stem loop did contribute to the encoding system and just with the emergence of the mRNA it was co-opted for codification. Thus, we present a model for the origin of the genetic code in which the operational and the anticodon codes did not evolve independently.
遗传密码的起源和进化是现代生物学的一个基本挑战。这个问题的核心是氨基酸和 tRNA 之间的正确相互作用。氨酰-tRNA 合成酶是负责氨基酸与 tRNA 正确结合的酶。在 20 种常见氨基酸中，甘氨酸在原始条件下最为丰富，它一定是最早被纳入遗传密码的氨基酸之一。在这项工作中，我们推导出甘氨酰-tRNA 合成酶（GlyRS）的祖先序列，并预测了它的 3D 结构。我们通过分子对接实验表明，祖先 GlyRS 能够结合 tRNA 反密码子茎环、辅助因子和底物。这些结合具有高亲和力和特异性。我们提出，这些相互作用的原始功能是稳定这两种化合物，从而实现催化。在这种情况下，反密码子茎环确实为编码系统做出了贡献，只是随着 mRNA 的出现，它才被共同用于编码。因此，我们提出了一个遗传密码起源的模型，其中操作码和反密码子码不是独立进化的。
