Folding, Assembly, and Persistence: The Essential Nature and Origins of Biopolymers

Abstract

Life as we know it requires three basic types of polymers: polypeptide, polynucleotide, and polysaccharide. Here we evaluate both universal and idiosyncratic characteristics of these biopolymers. We incorporate this information into a model that explains much about their origins, selection, and early evolution. We observe that all three biopolymer types are pre-organized, conditionally self-complementary, chemically unstable in aqueous media yet persistent because of kinetic trapping, with chiral monomers and directional chains. All three biopolymers are synthesized by dehydration reactions that are catalyzed by molecular motors driven by hydrolysis of phosphorylated nucleosides. All three biopolymers can access specific states that protect against hydrolysis. These protected states are folded, using self-complementary interactions among recurrent folding elements within a given biopolymer, or assembled, in associations between the same or different biopolymer types. Self-association in a hydrolytic environment achieves self-preservation. Heterogeneous association achieves partner-preservation. These universal properties support a model in which life’s polymers emerged simultaneously and co-evolved in a common hydrolytic milieu where molecular persistence depended on folding and assembly. We believe that an understanding of the structure, function, and origins of any given type of biopolymer requires the context of other biopolymers.

Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions

“…In this model, protein synthesis and protein folding coevolved along with the translation system. At the earliest stages, proto-peptide synthesis cooperated with differential rates of hydrolytic degradation, mediated by folding and assembly, to drive chemical evolution (1, 63–66). This model is consistent with incremental conversion of noncoded depsipeptides (which are unstructured, in part, due to their ester bonds, below) to coded polypeptide (which can fold to well-defined functional domains).…”

“…Coded protein is a linear polymer of 20 diverse amino acids, with a cohesive backbone that self-assembles via complementarity of H-bond acceptors and donors of the polypeptide backbone (1, 2). Proteins can fold spontaneously into “native” states with low configurational entropy and precise positioning of functional groups in 3D space.…”

“…In the RNA World hypothesis (16–20) and in coevolutionary RNA−protein models for the origins of life (1, 21–23), proto-protein interacted extensively with negatively charged RNA (or proto-RNA) (24) and perhaps directly catalyzed the oligomerization/ligation of RNA (21, 25). These models require cationic proto-peptides, i.e., oligomers that are positively charged, which would enable noncovalent assemblies based on stabilizing electrostatic interactions between protomers of peptide and RNA.…”

Water and Life: The Medium is the Message

“…Chemical transformations of water are widespread in the core chemistry of life, including biosynthesis of amino acids, nucleotides, and membrane components (Voet and Voet 2010 ). Water is chemically transformed during information processing, as in the synthesis of DNA (Patel et al 2011 ) and RNA (Belogurov and Artsimovitch 2015 ), and in synthesis of carbohydrates and phospholipids (Runnels et al 2018 ). Transformations of water are also key to central metabolism, in glycolysis, the citric acid cycle, oxidative phosphorylation, and photosynthesis (Voet and Voet 2010 ).…”

The Emergence of Life

“…At the second level, is the question as to how did the RNA world or RNA-peptide world get to the LUCA stage? The larger 'origins of life' questions are gradually evolving towards a more systemic approach that involves simultaneous roles of multiple components and their respective pathways in a coevolving network towards biocomplexity (de la Escosura et al 2015; Le Vay and Mutschler 2019; Runnels et al 2018). Bhowmik and Krishnamurthy (2019) have made a compelling case for the possibility of the concurrent emergence of both RNA and DNA from what they refer to as a "prebiotic clutter" of chemicals.…”