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.

Department of Biophysics Johns Hopkins University Baltimore MD 21212 USA

Department of Cell Biology Faculty of Science Charles University BIOCEV Prague 12800 Czech Republic

Department of Chemistry Johns Hopkins University Baltimore MD 21212 USA

Earth Life Science Institute Tokyo Institute of Technology Tokyo 1528550 Japan

Graduate School of Media and Governance Keio University Fujisawa 2520882 Japan

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague 16610 Czech Republic

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The interplay between peptides and RNA is critical for protoribosome compartmentalization and stability

Peptides En Route from Prebiotic to Biotic Catalysis

Early Selection of the Amino Acid Alphabet Was Adaptively Shaped by Biophysical Constraints of Foldability

Building the SynBio community in the Czech Republic from the bottom up: You get what you give