We present a testable hypothesis related to an origin of life on land in which fluctuating volcanic hot spring pools play a central role. The hypothesis is based on experimental evidence that lipid-encapsulated polymers can be synthesized by cycles of hydration and dehydration to form protocells. Drawing on metaphors from the bootstrapping of a simple computer operating system, we show how protocells cycling through wet, dry, and moist phases will subject polymers to combinatorial selection and draw structural and catalytic functions out of initially random sequences, including structural stabilization, pore formation, and primitive metabolic activity. We propose that protocells aggregating into a hydrogel in the intermediate moist phase of wet-dry cycles represent a primitive progenote system. Progenote populations can undergo selection and distribution, construct niches in new environments, and enable a sharing network effect that can collectively evolve them into the first microbial communities. Laboratory and field experiments testing the first steps of the scenario are summarized. The scenario is then placed in a geological setting on the early Earth to suggest a plausible pathway from life's origin in chemically optimal freshwater hot spring pools to the emergence of microbial communities tolerant to more extreme conditions in dilute lakes and salty conditions in marine environments. A continuity is observed for biogenesis beginning with simple protocell aggregates, through the transitional form of the progenote, to robust microbial mats that leave the fossil imprints of stromatolites so representative in the rock record. A roadmap to future testing of the hypothesis is presented. We compare the oceanic vent with land-based pool scenarios for an origin of life and explore their implications for subsequent evolution to multicellular life such as plants. We conclude by utilizing the hypothesis to posit where life might also have emerged in habitats such as Mars or Saturn's icy moon Enceladus. "To postulate one fortuitously catalyzed reaction, perhaps catalyzed by a metal ion, might be reasonable, but to postulate a suite of them is to appeal to magic." -Leslie Orgel.

The Hot Spring Hypothesis for an Origin of Life.

The fundamental roles that peptides and proteins play in today's biology makes it almost indisputable that peptides were key players in the origin of life. Insofar as it is appropriate to extrapolate back from extant biology to the prebiotic world, one must acknowledge the critical importance that interconnected molecular networks, likely with peptides as key components, would have played in life's origin. In this review, we summarize chemical processes involving peptides that could have contributed to early chemical evolution, with an emphasis on molecular interactions between peptides and other classes of organic molecules. We first summarize mechanisms by which amino acids and similar building blocks could have been produced and elaborated into proto-peptides. Next, non-covalent interactions of peptides with other peptides as well as with nucleic acids, lipids, carbohydrates, metal ions, and aromatic molecules are discussed in relation to the possible roles of such interactions in chemical evolution of structure and function. Finally, we describe research involving structural alternatives to peptides and covalent adducts between amino acids/peptides and other classes of molecules. We propose that ample future breakthroughs in origin-of-life chemistry will stem from investigations of interconnected chemical systems in which synergistic interactions between different classes of molecules emerge.

Prebiotic Peptides: Molecular Hubs in the Origin of Life.

Phosphate is central to the origin of life because it is a key component of nucleotides in genetic molecules, phospholipid cell membranes, and energy transfer molecules such as adenosine triphosphate. To incorporate phosphate into biomolecules, prebiotic experiments commonly use molar phosphate concentrations to overcome phosphate’s poor reactivity with organics in water. However, phosphate is generally limited to micromolar levels in the environment because it precipitates with calcium as low-solubility apatite minerals. This disparity between laboratory conditions and environmental constraints is an enigma known as “the phosphate problem.” Here we show that carbonate-rich lakes are a marked exception to phosphate-poor natural waters. In principle, modern carbonate-rich lakes could accumulate up to ∼0.1 molal phosphate under steady-state conditions of evaporation and stream inflow because calcium is sequestered into carbonate minerals. This prevents the loss of dissolved phosphate to apatite precipitation. Even higher phosphate concentrations (>1 molal) can form during evaporation in the absence of inflows. On the prebiotic Earth, carbonate-rich lakes were likely abundant and phosphate-rich relative to the present day because of the lack of microbial phosphate sinks and enhanced chemical weathering of phosphate minerals under relatively CO2-rich atmospheres. Furthermore, the prevailing CO2 conditions would have buffered phosphate-rich brines to moderate pH (pH 6.5 to 9). The accumulation of phosphate and other prebiotic reagents at concentration and pH levels relevant to experimental prebiotic syntheses of key biomolecules is a compelling reason to consider carbonate-rich lakes as plausible settings for the origin of life.

https://www.pnas.org/content/pnas/117/2/883.full.pdf

A carbonate-rich lake solution to the phosphate problem of the origin of life

We present a method for determining the free-energy dependence on a selected number of collective variables using an adaptive bias. The formalism provides a unified description which has metadynamics and canonical sampling as limiting cases. Convergence and errors can be rigorously and easily controlled. The parameters of the simulation can be tuned so as to focus the computational effort only on the physically relevant regions of the order parameter space. The algorithm is tested on the reconstruction of an alanine dipeptide free-energy landscape.

http://absimage.aps.org/image/MAR08/MWS_MAR08-2007-003737.pdf

Well-tempered metadynamics: a smoothly-converging and tunable free-energy method

Research on the origin of life is highly heterogeneous. After a peculiar historical development, it still includes strongly opposed views which potentially hinder progress. In the 1st Interdisciplinary Origin of Life Meeting, early-career researchers gathered to explore the commonalities between theories and approaches, critical divergence points, and expectations for the future. We find that even though classical approaches and theories—e.g., bottom-up and top-down, RNA world vs. metabolism-first—have been prevalent in origin of life research, they are ceasing to be mutually exclusive and they can and should feed integrating approaches. Here we focus on pressing questions and recent developments that bridge the classical disciplines and approaches, and highlight expectations for future endeavours in origin of life research.

/pdf/the-future-of-origin-of-life-research-bridging-decades-old-lafapl3iy9.pdf

The Future of Origin of Life Research: Bridging Decades-Old Divisions.

The membranes of the first protocells on the early Earth were likely self-assembled from fatty acids. A major challenge in understanding how protocells could have arisen and withstood changes in their environment is that fatty acid membranes are unstable in solutions containing high concentrations of salt (such as would have been prevalent in early oceans) or divalent cations (which would have been required for RNA catalysis). To test whether the inclusion of amino acids addresses this problem, we coupled direct techniques of cryoelectron microscopy and fluorescence microscopy with techniques of NMR spectroscopy, centrifuge filtration assays, and turbidity measurements. We find that a set of unmodified, prebiotic amino acids binds to prebiotic fatty acid membranes and that a subset stabilizes membranes in the presence of salt and Mg2+ Furthermore, we find that final concentrations of the amino acids need not be high to cause these effects; membrane stabilization persists after dilution as would have occurred during the rehydration of dried or partially dried pools. In addition to providing a means to stabilize protocell membranes, our results address the challenge of explaining how proteins could have become colocalized with membranes. Amino acids are the building blocks of proteins, and our results are consistent with a positive feedback loop in which amino acids bound to self-assembled fatty acid membranes, resulting in membrane stabilization and leading to more binding in turn. High local concentrations of molecular building blocks at the surface of fatty acid membranes may have aided the eventual formation of proteins.

https://www.pnas.org/content/pnas/116/35/17239.full.pdf

Prebiotic amino acids bind to and stabilize prebiotic fatty acid membranes

Adsorption of biomolecules onto material surfaces involves a potentially complex mechanism where molecular species interact to varying degrees with a heterogeneous material surface. Surface adsorption studies by atomic force microscopy, sum frequency generation spectroscopy, and solid-state NMR detect the structures and interactions of biomolecular species that are bound to material surfaces, which, in the absence of a solid-liquid interface, do not exchange rapidly between surface-bound forms and free molecular species in bulk solution. Solution NMR has the potential to complement these techniques by detecting and studying transiently bound biomolecules at the liquid-solid interface. Herein, we show that dark-state exchange saturation transfer (DEST) NMR experiments on gel-stabilized TiO2 nanoparticle (NP) samples detect several forms of biomolecular adsorption onto titanium(IV) oxide surfaces. Specifically, we use the DEST approach to study the interaction of amino acids arginine (Arg), lysine (Lys), leucine (Leu), alanine (Ala), and aspartic acid (Asp) with TiO2 rutile NP surfaces. Whereas Leu, Ala, and Asp display only a single weakly interacting form in the presence of TiO2 NPs, Arg and Lys displayed at least two distinct bound forms: a species that is surface bound and retains a degree of reorientational motion and a second more tightly bound form characterized by broadened DEST profiles upon the addition of TiO2 NPs. Molecular dynamics simulations indicate different surface bound states for both Lys and Arg depending on the degree of TiO2 surface hydroxylation but only a single bound state for Asp regardless of the degree of surface hydroxylation, in agreement with results obtained from the analysis of DEST profiles.

/pdf/studies-of-dynamic-binding-of-amino-acids-to-tio2-12bdsmtq3n.pdf

Studies of Dynamic Binding of Amino Acids to TiO2 Nanoparticle Surfaces by Solution NMR and Molecular Dynamics Simulations.

Dipeptides, which consist of two amino acids joined by a peptide bond, have been shown to have catalytic functions. This observation leads to fundamental questions relevant to the origin of life. How could peptides have become colocalized with the first protocells? Which structural features would have determined the association of amino acids and peptides with membranes? Could the association of dipeptides with protocell membranes have driven molecular evolution, favoring dipeptides over individual amino acids? Using pulsed-field gradient nuclear magnetic resonance, we find that several prebiotic amino acids and dipeptides bind to prebiotic membranes. For amino acids, the side chains and carboxylate contribute to the interaction. For dipeptides, the extent of binding is generally less than that of the constituent amino acids, implying that other mechanisms would be necessary to drive molecular evolution. Nevertheless, our results are consistent with a scheme in which the building blocks of the biological polymers colocalized with protocells prior to the emergence of RNA and proteins.

Binding of Dipeptides to Fatty Acid Membranes Explains Their Colocalization in Protocells but Does Not Select for Them Relative to Unjoined Amino Acids.

A major challenge in understanding how biological cells arose on the early Earth is explaining how RNA and membranes originally colocalized. We propose that the building blocks of RNA (nucleobases and ribose) bound to self-assembled prebiotic membranes. We have previously demonstrated that the bases bind to membranes composed of a prebiotic fatty acid, but evidence for the binding of sugars has remained a technical challenge. Here, we used pulsed-field gradient NMR spectroscopy to demonstrate that ribose and other sugars bind to membranes of decanoic acid. Moreover, the binding of some bases is strongly enhanced when they are linked to ribose to form a nucleoside or - with the addition of phosphate - a nucleotide. This enhanced binding could have played a role in the molecular evolution leading to the production of RNA.

https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/cbic.202000638

Mengjun Xue

Papers

Prebiotic amino acids bind to and stabilize prebiotic fatty acid membranes

Studies of Dynamic Binding of Amino Acids to TiO2 Nanoparticle Surfaces by Solution NMR and Molecular Dynamics Simulations.

Binding of Dipeptides to Fatty Acid Membranes Explains Their Colocalization in Protocells but Does Not Select for Them Relative to Unjoined Amino Acids.

A Step toward Molecular Evolution of RNA: Ribose Binds to Prebiotic Fatty Acid Membranes, and Nucleosides Bind Better than Individual Bases Do.