A Peptide–Nucleic Acid Replicator Origin for Life

Abstract

Evolution requires self-replication. But, what was the very first self-replicator directly ancestral to all life? The currently favoured RNA World theory assigns this role to RNA alone but suffers from a number of seemingly intractable problems. Instead, we suggest that the self-replicator consisted of both peptides and nucleic acid strands. Such a nucleopeptide replicator is more feasible both in the light of the replication machinery currently found in cells and the complexity of the evolutionary path required to reach them. Recent theoretical and mathematical work supports this idea and provide a blueprint for future investigations. The Ancestral ReplicatorLife as we understand it is cellular. The last universal common ancestor (LUCA) of all cells (not a single cell of course but a population) is understood in some detail; it possessed a cell membrane, DNA, the basic molecular machines for copying DNA (i.e., polymerase etc.), and a functional ribosome, among many more [1]. From this highly truncated list alone it is clear that LUCA was far too complex to spontaneously assemble. It must have evolved from simpler systems, themselves able to self-replicate with some tolerance for error (otherwise they would not be able to evolve). Indeed, it is difficult to imagine that anything recognisably a cell could have spontaneous origins. This means that they in turn must have evolved from even simpler self replicators; that is, molecular selfreplicators. The first such replicator is referred to as the initial Darwinian ancestor (IDA) [2].The identity of the IDA has been cause for much speculation over the years. Nonbiological replicators such as clay crystals [3] have been invoked but are unconvincing as they require a complete takeover of one substrate with another and lack a persuasive argument to show how this could have occurred. An IDA built from biological molecules is more convincing and necessitates physicochemical conditions compatible with their formation, and with the self-replicating reaction cycle of the IDA itself. The latter likely required relatively mild conditions approaching those of analogous biochemical reactions today. There is now ample evidence that biological building blocks such as amino acids, ribose, and deoxyribose, among others, were present on the early Earth [4][5][6][7]. Potential chemistries for building block synthesis have been demonstrated, with cyanosulfidic chemistry [8] showing great promise. Furthermore, recent work has shown convincing peptide ligation in prebiotic conditions [9]. Given these findings, it now seems reasonable to assume that the IDA was constructed of components highly similar or identical to those found in life today. Indeed, such a replicator must have occurred at some stage very early in evolution even if not at the very beginning. The scene being set for an IDA constructed of biological molecules to arise, our focus turns to the main issue of this workdeciding on its identity. Three approaches will be useful to us in this endeavour. (i) Consideration of curren...

Emerging low-molecular weight nucleopeptide-based hydrogels: state of the art, applications, challenges and perspectives

“…43,44 Thus, thanks to the wealth of possibilities for the modulation of the two constitutive parts, i.e., the peptide (e.g., length, sequence, nature of the amino acids) and the nucleobase-containing (e.g., number, sequence, position in the peptide, nature of the base, type of derivative considered) moieties, nucleopeptides appear as a highly versatile class of molecules with almost virtually infinite possibilities in terms of design and molecular structures, offering to chemists a fascinating field to explore and to understand. 29 While not found in Nature (except for the nucleoamino acid willardiine) and that their prebiotic role has been hypothesized, [45][46][47] nucleopeptides are mainly synthetic compounds developed for biological applications 47 thanks to their ability to interact with proteins or enzymes such as serum albumin 48 or the reverse-transcriptase of HIV. 49 Harnessing the abilities of peptides and nucleobases to self-assemble in specific conditions, several research groups reported on the use of nucleopeptides to study their self-organisation and to develop new properties and applications 29 such as tuneable or functional supramolecular architectures, [50][51][52][53] fluorescence, [54][55][56][57] to selectively sequestrate ATP in cells 58 or to deliver RNA into cells, 59 to name a few.…”

Protein-Free ribosomal RNA scaffolds can assemble poly-lysine oligos from charged tRNA fragments

“…Therefore, a peptide/nucleic acid co-evolution route is possible, as suggested in the literature. [25] Theoretic study has suggested that optimizing the interaction between RNA's double helix and peptide's -sheet could drive the evolution of both species without sequencing fidelity. [16] Indeed, diverse RNA sequences can form similar structural modules.…”

Genome Evolution from Random Ligation of RNAs of Autocatalytic Sets

“…Given this rich catalytic repertoire of ribozymes the RNA world scenario seems plausible and even likely to have existed in the form of ribozyme-catalyzed metabolisms [42]. However, the evolution of the first replicator remains an unsolved problem, as no selfreplicating RNA has been identified to date [43]. The closest to an experimentally verified self-replicating RNA system has been a set of two RNA ligase ribozymes that catalyze each other's formation (a simple autocatalytic set), which however requires complex preformed RNA building blocks [44].…”