Peptides before and during the nucleotide world: an origins story emphasizing cooperation between proteins and nucleic acids

Abstract

Recent developments in Origins of Life research have focused on substantiating the narrative of an abiotic emergence of nucleic acids from organic molecules of low molecular weight, a paradigm that typically sidelines the roles of peptides. Nevertheless, the simple synthesis of amino acids, the facile nature of their activation and condensation, their ability to recognize metals and cofactors and their remarkable capacity to self-assemble make peptides (and their analogues) favourable candidates for one of the earliest functional polymers. In this mini-review, we explore the ramifications of this hypothesis. Diverse lines of research in molecular biology, bioinformatics, geochemistry, biophysics and astrobiology provide clues about the progression and early evolution of proteins, and lend credence to the idea that early peptides served many central prebiotic roles before they were encodable by a polynucleotide template, in a putative ‘peptide-polynucleotide stage’. For example, early peptides and mini-proteins could have served as catalysts, compartments and structural hubs. In sum, we shed light on the role of early peptides and small proteins before and during the nucleotide world, in which nascent life fully grasped the potential of primordial proteins, and which has left an imprint on the idiosyncratic properties of extant proteins.

Uniform binding and negative catalysis at the origin of enzymes

“…These motifs possess characteristics suggesting that they emerged in the context of the primordial protein world (Figure 2). Overall, it appears that phosphate binding is one of the earliest, if not the earliest, protein function—a function that was exhibited by polypeptides in a primordial world that was based on nucleic acids, amino acids and short peptides, that is, the “peptide‐polynucleotide world” 8,33 . It is conceivable that these short peptides emerged following an “RNA world” in which both catalysis and genetic information storage were carried out by RNA molecules called ribozymes.…”

Protobiotic network reproducers are compositional attractors: enhanced probability for life’s origin

“…The first school assumes that life began with a small repertoire of molecules similar in structure and function to those found in today's life, e.g. very specific subsets of nucleobases and amino acids, as well as linear polymers thereof (4,5). This top-down realm seeks prebiotic synthesis paths that could yield such life-like molecules (6).…”

Folding and Evolution of a Repeat Protein on the Ribosome

“…And what is more, the sub-domain sized fragments have been found in very distant pairs of proteins that are not considered homologous; therefore these recurring themes could be traced over evolutionary time to ( Bowman et al, 2020 ) the origin of the ribosome itself or even to a pre-ribosomal world lacking modern protein translation ( Caetano-Anolles et al, 2009 ). Repetitive themes that homo-oligomerize to form soluble mini proteins could have characterized this early peptide-polynucleotide stage of protein fold evolution ( Fried et al, 2022 ).…”