Organization of Nucleotides in Different Environments and the Formation of Pre-Polymers

Abstract

RNA is a linear polymer of nucleotides linked by a ribose-phosphate backbone. Polymerization of nucleotides occurs in a condensation reaction in which phosphodiester bonds are formed. However, in the absence of enzymes and metabolism there has been no obvious way for RNA-like molecules to be produced and then encapsulated in cellular compartments. We investigated 5′-adenosine monophosphate (AMP) and 5′-uridine monophosphate (UMP) molecules confined in multi-lamellar phospholipid bilayers, nanoscopic films, ammonium chloride salt crystals and Montmorillonite clay, previously proposed to promote polymerization. X-ray diffraction was used to determine whether such conditions imposed a degree of order on the nucleotides. Two nucleotide signals were observed in all matrices, one corresponding to a nearest neighbour distance of 4.6 Å attributed to nucleotides that form a disordered, glassy structure. A second, smaller distance of 3.4 Å agrees well with the distance between stacked base pairs in the RNA backbone, and was assigned to the formation of pre-polymers, i.e., the organization of nucleotides into stacks of about 10 monomers. Such ordering can provide conditions that promote the nonenzymatic polymerization of RNA strands under prebiotic conditions. Experiments were modeled by Monte-Carlo simulations, which provide details of the molecular structure of these pre-polymers.

The Hot Spring Hypothesis for an Origin of Life

“…The above scenario provides a platform available to experimental testing. Indeed, the first steps of this scenario have been confirmed: the stabilizing effect of initially random polymers on protocells allows elongation and potential amplification of those polymers (Rajamani et al, 2008;da Silva et al, 2014;DeGuzman et al, 2014;Himbert et al, 2016;Deamer et al, 2019). While the emergence of pores or metabolic cycles has not yet been demonstrated, poreforming polymers could be observed in future experiments carried out through multiple cycles under a number of conditions.…”

“…Recent investigations of a 3.5 billion-year-old, anoxic hot spring setting from the Pilbara Craton in Western Australia show that its hydrothermal veins and compositionally varied pools and springs had the capacity to mobilize and concentrate many of the elements required for prebiotic chemistry, including C, H, N, O, P, S, B, Zn, Mn, K, and others (Van Kranendonk et al, 2020). As described earlier, biological polymers such as oligonucleotides and oligopeptides are products of condensation reactions and can be synthesized when their solutions are exposed to multiple wet-dry cycles in acidic fresh water (Rajamani et al, 2008;Toppozini et al, 2013;da Silva et al, 2014;DeGuzman et al, 2014;Forsythe et al, 2015;Rodriguez-Garcia et al, 2015;Himbert et al, 2016;Misuraca et al, 2017;Yu et al, 2017). Mineral surfaces and peptides may play roles such as nonenzymatic polymerization in early steps in life's origins and bear further investigation (Dalai and Sahai, 2018;Kaddour et al, 2018).…”

Mobility of a Mononucleotide within a Lipid Matrix: A Neutron Scattering Study

“…The question then concerns the physical state of the AMP in the dehydration phase when dry carbon dioxide at 0% RH is passed over the samples at 358 K. It is obvious that no free water will remain in the sample under those conditions. Furthermore, from previous studies using X-ray diffraction [12,26], it is also clear that the AMP in the lipid matrix is not in a disordered glassy state but instead has a significant degree of order, either as paracrystalline arrays (pure AMP) or with base stacking (AMP:UMP in a 1:1 mole ratio mixture). This degree of order could not be present if the nucleotides were freely diffusing, in agreement with the neutron scattering results at h < 35%.…”

Binary Encoding of Random Peptide Sequences for Selective and Differential Antimicrobial Mechanisms

“…To further understand this non‐responsive mode of folding, CD spectra were obtained for the mixtures in reconstituted membranes . Anionic and zwitterionic unilamellar vesicles, AUVs and ZUVs, respectively, provided microbial and mammalian membrane mimetics, while weakly anionic AUVs (wAUVs) emulated erythrocytal membranes (see the Supporting Information). In all of these cases, only additive changes in the negative bands for the AUV samples were observed, suggesting marginal contributions from membrane binding (Figure S2).…”