Open Questions in Origin of Life: Experimental Studies on the Origin of Nucleic Acids and Proteins With Specific and Functional Sequences by a Chemical Synthetic Biology Approach

Abstract

In this mini-review we present some experimental approaches to the important issue in the origin of life, namely the origin of nucleic acids and proteins with specific and functional sequences. The formation of macromolecules on prebiotic Earth faces practical and conceptual difficulties. From the chemical viewpoint, macromolecules are formed by chemical pathways leading to the condensation of building blocks (amino acids, or nucleotides) in long-chain copolymers (proteins and nucleic acids, respectively). The second difficulty deals with a conceptual problem, namely with the emergence of specific sequences among a vast array of possible ones, the huge “sequence space”, leading to the question “why these macromolecules, and not the others?”We have recently addressed these questions by using a chemical synthetic biology approach. In particular, we have tested the catalytic activity of small peptides, like Ser-His, with respect to peptide- and nucleotides-condensation, as a realistic model of primitive organocatalysis. We have also set up a strategy for exploring the sequence space of random proteins and RNAs (the so-called “never born biopolymer” project) with respect to the production of folded structures. Being still far from solved, the main aspects of these “open questions” are discussed here, by commenting on recent results obtained in our groups and by providing a unifying view on the problem and possible solutions. In particular, we propose a general scenario for macromolecule formation via fragment-condensation, as a scheme for the emergence of specific sequences based on molecular growth and selection.

Surveying the sequence diversity of model prebiotic peptides by mass spectrometry

“…Internal sequence stretches for g+G+A+L and a+G+A+L tetramers demonstrated high sequence diversity after only 4 d of reaction. The observation of more diverse tetramers as the system evolved is consistent with the hypothesis that a vast array of sequences may have been present on the prebiotic earth before the initiation of template-directed peptide synthesis (47,48). When considering a prebiotic timescale, it seems reasonable to conclude that proto-peptides of short to moderate length would have had sufficient time to diversify into an innumerable set of sequences.…”

Evolutionary convergence in the biosyntheses of the imidazole moieties of histidine and purines

“…Histidyl-histidine (His-His) catalyzes the dephosphorylation of deoxyribonucleoside monophosphate, the hydrolysis of oligo (A) 12 , and the oligomerization of 2',3'-cAMP under cyclic wet-dry reaction conditions [ 25 ]. More recent studies have shown that seryl-histidine (Ser-His) catalyzes the oligomerization of trimers of imidazole-activated nucleotides [ 26 , 27 ], and catalyze peptide bond formation between two amino acids, an activity also found in seryl-histidyl-glycine (Ser-His-Gly) [ 28 , 29 ].…”

Earth's Early Atmosphere and Oceans, and The Origin of Life

“…It is worthwhile noting that polymerization of RNA from monomers and self-replication of small RNA units has received considerable attention from experimentalists (Bowler et al 2013;Adamala and Szostak 2013;Adamala et al 2014), including those looking for self-replication of RNA in extant organisms. The presence of an RNA template, say a small RNA polymer such as tRNA, may itself catalyze its own duplication by serving as a template for the assembly of a complementary strand from monomers in the surrounding medium.…”