Amino Acid Modified RNA Bases as Building Blocks of an Early Earth RNA‐Peptide World

Fossils of extinct species allow us to reconstruct the process of Darwinian evolution that led to the species diversity we see on Earth today. The origin of the first functional molecules able to undergo molecular evolution and thus eventually able to create life, are largely unknown. The most prominent idea in the field posits that biology was preceded by an era of molecular evolution, in which RNA molecules encoded information and catalysed their own replication. This RNA world concept stands against other hypotheses, that argue for example that life may have begun with catalytic peptides and primitive metabolic cycles. The question whether RNA or peptides were first is addressed by the RNA‐peptide world concept, which postulates a parallel existence of both molecular species. A plausible experimental model of how such an RNA‐peptide world may have looked like, however, is absent. Here we report the synthesis and physicochemical evaluation of amino acid containing adenosine bases, which are closely related to molecules that are found today in the anticodon stem‐loop of tRNAs from all three kingdoms of life. We show that these adenosines lose their base pairing properties, which allow them to equip RNA with amino acids independent of the sequence context. As such we may consider them to be living molecular fossils of an extinct molecular RNA‐peptide world. Naturally occurring amino acid containing nucleobases could be vestiges of an extinct early Earth RNA‐peptide world. Today they help to translate genetic information, but in the RNA‐peptide world, they might have been the units that equipped RNA with broad catalytic functions. These genotype‐phenotype bridging nucleosides were synthesized, and their properties were investigated. This study shows that these nucleosides do not base pair, which allows them to position amino acids in unpaired parts of complex RNA structures.