Trinity of G-tetrads and origin of translation

Abstract

Abstract Background The RNA world hypothesis cannot address most of the questions of the origin of life without violating the continuity principle (small Darwinian steps without foresight and miracles). Moreover, the RNA world is an isolated system incapable of accommodating the genetic code and evolving into extant biochemistry. All these problems are rooted in the central assumption of the hypothesis: de novo appearance of the ribozymes, production of which represents a multistep reaction requiring the complementarity principle. Thus, even the basis of the RNA world is at odds with the continuity principle—it uses foresight (multistep reaction) and a miracle (complementarity principle). Can a three-dimensional (3D) architecture, capable of molecular recognition and catalysis, be formed in a single-step reaction without the complementarity or any other preexisting rules? Hypothesis At first glance, the above question sounds rhetoric since the complementarity principle is the essential feature of the RNA world; it turns an RNA polymer into a genetic material. Without it, the RNA world becomes as shapeless and unconvincing as other hypotheses based on the non-hereditary molecules (i.e., protein world). However, it was suggested recently that the quadruplexes could initiate life and take necessary evolutionary steps before the arrival of the complementarity rules. The hypothesis relies on the unique properties of guanines (Gs) to self-assemble into G-tetrads and efficiently polymerize without any external help or preexisting rules. Interestingly, polyG folds into an unusually stable and well-structured monomolecular architecture that uses the quadruplex domain (QD) assembly. The QD has a strictly defined zigzag-like building pattern to accommodate only three G-tetrads. Since both QD architecture and codon length are based on triplets, the inevitable question arises: are they related? Or could QD play the role of the early adapter and determine the codon length? The current paper is an attempt to answer this question. Conclusion While without translation apparatus most of the steps of the extant translation are physically impossible, the QD-mediated translation is sterically feasible and can be explained by physicochemical properties of the QD and the amino acids without violating the continuity principle. Astonishingly, the quadruplex world hypothesis can address all the shortcomings of the RNA world, including its most significant challenge—step-by-step evolution from the polymerization of the first polynucleotide to the extant biochemistry.