Alkaline saline lakes: A chemical evolution experiment evaluating the stability of formaldehyde in an aqueous saline environment.

Formaldehyde condensation in the presence of a mineral catalyst and under alkaline conditions is considered to be a "messy" chemical system due to its dependence on the complex chemical equilibrium between the reaction intermediates, which has a significant impact on the final products. This chemical system is extremely important in prebiotic chemistry and has been proposed as a potential pathway for carbohydrate formation in the early Earth. Saline and soda lakes are alkaline systems that could concentrate and accumulate a wide variety of ions (such as phosphate) and clay minerals, which can catalyze prebiotic chemical reactions. These geological environments have recently been suggested as ideal environments in which prebiotic chemical reactions could have occurred. This study uses Lake Alchichica in Mexico as a physicochemical analog of an early Archean saline lake to examine the stability of formaldehyde in these aqueous saline environments. Formaldehyde decomposes into sugar-like and CHO molecules in alkaline, high-salinity environments depending on the minerals phases present. As phosphate ion (HPO4 2-) is available in the aqueous medium, the results of our experiments also imply that phosphorylation processes may have occurred in these natural settings.

Selection in molecular evolution.

Evolution requires selection. Molecular/chemical/preDarwinian evolution is no exception. One molecule must be selected over another for molecular evolution to occur and advance. Evolution, however, has no goal. The laws of physics have no utilitarian desire, intent or proficiency. Laws and constraints are blind to "usefulness." How then were potential multi-step processes anticipated, valued and pursued by inanimate nature? Can orchestration of formal systems be physico-chemically spontaneous? The purely physico-dynamic self-ordering of Chaos Theory and irreversible non-equilibrium thermodynamic "engines of disequilibria conversion" achieve neither orchestration nor formal organization. Natural selection is a passive and after-the-fact-of-life selection. Darwinian selection reduces to the differential survival and reproduction of the fittest already-living organisms. In the case of abiogenesis, selection had to be 1) Active, 2) Pre-Function, and 3) Efficacious. Selection had to take place at the molecular level prior to the existence of non-trivial functional processes. It could not have been passive or secondary. What naturalistic mechanisms might have been at play?

Evolution of Acquired Perfumes and Endogenous Lipid Secretions in Orchid Bees.

Male orchid bees are unique in the animal kingdom for making perfumes that function as sex pheromone. Males collect volatile chemicals from the environment in the neotropical forests, including floral and non-floral sources, creating complex but species-specific blends. Male orchid bees exhibit several adaptations to facilitate perfume collection and storage. When collecting volatile compounds, males apply lipid substances that they secrete from cephalic labial glands onto the fragrant substrate. These lipids help dissolve and retain the volatiles, similar to the process of 'enfleurage' in the traditional perfume industry. We investigated how the chemical composition of acquired perfume and labial gland secretions varied across the phylogeny of orchid bees, including 65 species in five genera from Central and South America. Perfumes showed rapid evolution as revealed by low overall phylogenetic signal, in agreement with the idea that perfume compounds diverge rapidly and substantially among closely related species due to their role in species recognition. A possible exception were perfumes in the genus Eulaema, clustering closely in chemospace, partly mediated by high proportions of carvone and trans-carvone oxide. Labial gland secretions, in contrast, showed a strong phylogenetic signal at the genus level, with secretions of Eufriesea and Exaerete dominated by fatty acids and Eulaema dominated by saturated acetates of chain lengths 12 to 16 C-atoms. Secretions of the majority of Euglossa were heavily dominated by one unsaturated long chain diacetate, (9Z)-Eicosen-1,20-diyldiacetate. However, we also identified few highly divergent species of Euglossa in four subclades (11 species) that appear to have secondarily replaced the diacetate with other compounds. In comparison with environment-derived perfumes, the evolution of labial gland secretion is much slower, likely constrained by the underlying biochemical pathways, but perhaps influenced by perfume-solvent chemical interactions.

Programmable Chemical Evolution with Natural/non-natural Building Blocks.

Non-natural building blocks (BBs) present a vast reservoir of chemical diversity for molecular recognition and drug discovery. However, leveraging evolutionary principles to efficiently generate bioactive molecules with a larger number of diverse BBs poses challenges within current laboratory evolution systems. Here, we introduce programmable chemical evolution (PCEvo) by integrating chemoinformatic classification and high-throughput array synthesis/screening. PCEvo initiates evolution by constructing a diversely combinatorial library to create ancestral molecules, streamlines the molecular evolution process and identifies high-affinity binders within 2-4 cycles. By employing PCEvo with 108 BBs and exploring >10^17 chemical space, we identify bicyclic peptidomimetic binders against targets SAR-CoV-2 RBD and Claudin18.2, achieving nanomolar affinity. Remarkably, Claudin18.2 binders selectively stain gastric adenocarcinoma cell lines and patient samples. PCEvo achieves expedited evolution in a few rounds, marking a significant advance in utilizing non-natural building blocks for rapid chemical evolution applicable to targets with or without prior structural information and ligand preference.

The Mystery of Homochirality on Earth.

Homochirality is an obvious feature of life on Earth. On the other hand, extraterrestrial samples contain largely racemic compounds. The same is true for any common organic synthesis. Therefore, it has been a perplexing puzzle for decades how these racemates could have formed enantiomerically enriched fractions as a basis for the origin of homochiral life forms. Numerous hypotheses have been put forward as to how preferentially homochiral molecules could have formed and accumulated on Earth. In this article, it is shown that homochirality of the abiotic organic pool at the time of formation of the first self-replicating molecules is not necessary and not even probable. It is proposed to abandon the notion of a molecular ensemble and to focus on the level of individual molecules. Although the formation of the first self-replicating, most likely homochiral molecule, is a seemingly improbable event, on a closer look, it is almost inevitable that some homochiral molecules have formed simply on a statistical basis. In this case, the non-selective leap to homochirality would be one of the first steps in chemical evolution directly out of a racemic "ocean". Moreover, most studies focus on the chirality of the primordial monomers with respect to an asymmetric carbon atom. However, any polymer with a minimal size that allows folding to a secondary structure would spontaneously lead to asymmetric higher structures (conformations). Most of the functions of these polymers would be influenced by this inherently asymmetric folding. Furthermore, a concept of physical compartmentalization based on rock nanopores in analogy to nanocavities of digital immunoassays is introduced to suggest that complex cell walls or membranes were also not required for the first steps of chemical evolution. To summarize, simple and universal mechanisms may have led to homochiral self-replicating systems in the context of chemical evolution. A homochiral monomer pool is deemed unnecessary and probably never existed on primordial Earth.

Evolution at the Origins of Life?

The role of evolutionary theory at the origin of life is an extensively debated topic. The origin and early development of life is usually separated into a prebiotic phase and a protocellular phase, ultimately leading to the Last Universal Common Ancestor. Most likely, the Last Universal Common Ancestor was subject to Darwinian evolution, but the question remains to what extent Darwinian evolution applies to the prebiotic and protocellular phases. In this review, we reflect on the current status of evolutionary theory in origins of life research by bringing together philosophy of science, evolutionary biology, and empirical research in the origins field. We explore the various ways in which evolutionary theory has been extended beyond biology; we look at how these extensions apply to the prebiotic development of (proto)metabolism; and we investigate how the terminology from evolutionary theory is currently being employed in state-of-the-art origins of life research. In doing so, we identify some of the current obstacles to an evolutionary account of the origins of life, as well as open up new avenues of research.

Synthetic Matching of Complex Monoterpene Indole Alkaloid Chemical Space.

Monoterpene indole alkaloids (MIAs) are endowed with high structural and spatial complexity and characterized by diverse biological activities. Given this complexity-activity combination in MIAs, rapid and efficient access to chemical matter related to and with complexity similar to these alkaloids would be highly desirable, since such compound classes might display novel bioactivity. We describe the design and synthesis of a pseudo-natural product (pseudo-NP) collection obtained by the unprecedented combination of MIA fragments through complexity-generating transformations, resulting in arrangements not currently accessible by biosynthetic pathways. Cheminformatic analyses revealed that both the pseudo-NPs and the MIAs reside in a unique and common area of chemical space with high spatial complexity-density that is only sparsely populated by other natural products and drugs. Investigation of bioactivity guided by morphological profiling identified pseudo-NPs that inhibit DNA synthesis and modulate tubulin. These results demonstrate that the pseudo-NP collection occupies similar biologically relevant chemical space that Nature has endowed MIAs with.

Assembly-driven protection from hydrolysis as key selective force during chemical evolution.

The origins of biopolymers pose fascinating questions in prebiotic chemistry. The marvelous assembly proficiencies of biopolymers suggest they are winners of a competitive evolutionary process. Sophisticated molecular assembly is ubiquitous in life where it is often emergent upon polymerization. We focus on the influence of molecular assembly on hydrolysis rates in aqueous media and suggest that assembly was crucial for biopolymer selection. In this model, incremental enrichment of some molecular species during chemical evolution was partially driven by the interplay of kinetics of synthesis and hydrolysis. We document a general attenuation of hydrolysis by assembly (i.e., recalcitrance) for all universal biopolymers and highlight the likely role of assembly in the survival of the 'fittest' molecules during chemical evolution.

Is Darwinian selection a retrograde driving force of evolution?

Modern science has still not provided a satisfactory empirical explanation for the increasing complexity of living organisms through evolutionary history. As no agreed-upon definitions of the complexity exist, the working definition of biological complexity has been formulated. There is no theoretical reason to expect evolutionary lineages to increase in complexity over time, and there is no empirical evidence that they do so. In our discussion we have assumed the hypothesis that at the origins of life, evolution had to first involve autocatalytic systems that only subsequently acquired the capacity of genetic heredity. We discuss the role of Darwinian selection in evolution and pose the hypothesis that Darwinian selection acts predominantly as a retrograde driving force of evolution. In this context we understand the term retrograde evolution as a degeneration of living systems from higher complexity towards living systems with lower complexity. With the proposed hypothesis we have closed the gap between Darwinism and Lamarckism early in the evolutionary process. By Lamarckism, the action of a special principle called complexification force is understood here rather than inheritance of acquired characteristics.

Serpentinization-Associated Mineral Catalysis of the Protometabolic Formose System.

The formose reaction is a plausible prebiotic chemistry, famed for its production of sugars. In this work, we demonstrate that the Cannizzaro process is the dominant process in the formose reaction under many different conditions, thus necessitating a catalyst for the formose reaction under various environmental circumstances. The investigated formose reactions produce primarily organic acids associated with metabolism, a protometabolic system, and yield very little sugar left over. This is due to many of the acids forming from the degradation and Cannizaro reactions of many of the sugars produced during the formose reaction. We also show the heterogeneous Lewis-acid-based catalysis of the formose reaction by mineral systems associated with serpentinization. The minerals that showed catalytic activity include olivine, serpentinite, and calcium, and magnesium minerals including dolomite, calcite, and our Ca/Mg-chemical gardens. In addition, computational studies were performed for the first step of the formose reaction to investigate the reaction of formaldehyde, to either form methanol and formic acid under a Cannizzaro reaction or to react to form glycolaldehyde. Here, we postulate that serpentinization is therefore the startup process necessary to kick off a simple proto metabolic system-the formose protometabolic system.

Gamma irradiation of adenine and guanine adsorbed into hectorite and attapulgite.

This study focuses on the radiolysis (up to 36 kGy) of guanine and adenine (nitrogenous bases) adsorbed in hectorite and attapulgite to highlight the potential role of clays as protective agents against ionizing radiation in prebiotic processes. In this framework, the study investigated the nitrogenous bases' behavior in two types of systems: a) aqueous suspension of adenine-clay systems and b) guanine-clay systems in the solid state. This research utilized spectroscopic and chromatographic techniques for its analytical purposes. Regardless of the reaction medium conditions, the results reveal that nitrogenous bases are stable under ionizing irradiation when adsorbed on both clays.

Radical reactions on interstellar icy dust grains: Experimental investigations of elementary processes.

Molecular clouds (MCs) in space are the birthplace of various molecular species. Chemical reactions occurring on the cryogenic surfaces of cosmic icy dust grains have been considered to play important roles in the formation of these species. Radical reactions are crucial because they often have low barriers and thus proceed even at low temperatures such as ∼10 K. Since the 2000s, laboratory experiments conducted under low-temperature, high-vacuum conditions that mimic MC environments have revealed the elementary physicochemical processes on icy dust grains. In this review, experiments conducted by our group in this context are explored, with a focus on radical reactions on the surface of icy dust analogues, leading to the formation of astronomically abundant molecules such as H2, H2O, H2CO, and CH3OH and deuterium fractionation processes. The development of highly sensitive, non-destructive methods for detecting adsorbates and their utilization for clarifying the behavior of free radicals on ice, which contribute to the formation of complex organic molecules, are also described.

Abiogenesis through gradual evolution of autocatalysis into template-based replication.

How life emerged from inanimate matter is one of the most intriguing questions posed to modern science. Central to this research are experimental attempts to build systems capable of Darwinian evolution. RNA catalysts (ribozymes) are a promising avenue, in line with the RNA world hypothesis whereby RNA pre-dated DNA and proteins. Since evolution in living organisms relies on template-based replication, the identification of a ribozyme capable of replicating itself (an RNA self-replicase) has been a major objective. However, no self-replicase has been identified to date. Alternatively, autocatalytic systems involving multiple RNA species capable of ligation and recombination may enable self-reproduction. However, it remains unclear how evolution could emerge in autocatalytic systems. In this review, we examine how experimentally feasible RNA reactions catalysed by ribozymes could implement the evolutionary properties of variation, heredity and reproduction, and ultimately allow for Darwinian evolution. We propose a gradual path for the emergence of evolution, initially supported by autocatalytic systems leading to the later appearance of RNA replicases.

Plausibility of the Formose Reaction in Alkaline Hydrothermal Vent Environments.

Prebiotic processes required a reliable source of free energy and complex chemical mixtures that may have included sugars. The formose reaction is a potential source of those sugars. At moderate to elevated temperature and pH ranges, these sugars rapidly decay. Here it is shown that CaCO3-based chemical gardens catalyze the formose reaction to produce glucose, ribose, and other monosaccharides. These thin inorganic membranes are explored as analogs of hydrothermal vent materials-a possible place for the origin of life-and similarly exposed to very steep pH gradients. Supported by simulations of a simple reaction-diffusion model, this study shows that such gradients allow for the dynamic accumulation of sugars in specific layers of the thin membrane, effectively protecting formose sugar yields. Therefore, the formose reaction may be a plausible prebiotic reaction in alkaline hydrothermal vent environments, possibly setting the stage for an RNA world.

Organophosphorus Compound Formation Through the Oxidation of Reduced Oxidation State Phosphorus Compounds on the Hadean Earth.

Reduced oxidation state phosphorus compounds may have been brought to the early Earth via meteorites or could have formed through geologic processes. These compounds could have played a role in the origin of biological phosphorus (P, hereafter) compounds. Reduced oxidation state P compounds are generally more soluble in water and are more reactive than orthophosphate and its associated minerals. However, to date no facile routes to generate C-O-P type compounds using reduced oxidation state P compounds have been reported under prebiotic conditions. In this study, we investigate the reactions between reduced oxidation state P compounds-and their oxidized products generated via Fenton reactions-with the nucleosides uridine and adenosine. The inorganic P compounds generated via Fenton chemistry readily react with nucleosides to produce organophosphites and organophosphates, including phosphate diesters via one-pot syntheses. The reactions were facilitated by NH4+ ions and urea as a condensation agent. We also present the results of the plausible stability of the organic compounds such as adenosine in an environment containing an abundance of H2O2. Such results have direct implications on finding organic compounds in Martian environments and other rocky planets (including early Earth) that were richer in H2O2 than O2. Finally, we also suggest a route for the sink of these inorganic P compounds, as a part of a plausible natural P cycle and show the possible formation of secondary phosphate minerals such as struvite and brushite on the early Earth.

Natural Radioactivity and Chemical Evolution on the Early Earth: Prebiotic Chemistry and Oxygenation.

It is generally recognized that the evolution of the early Earth was affected by an external energy source: radiation from the early Sun. The hypothesis about the important role of natural radioactivity, as a source of internal energy in the evolution of the early Earth, is considered and substantiated in this work. The decay of the long-lived isotopes 232Th, 238U, 235U, and 40K in the Global Ocean initiated the oxygenation of the hydro- and atmosphere, and the abiogenesis. The content of isotopes in the ocean and the kinetics of their decay, the values of the absorbed dose and dose rate, and the efficiency of sea water radiolysis, as a function of time, were calculated. The ocean served as both a "reservoir" that collected components of the early atmosphere and products of their transformations, and a "converter" in which further chemical reactions of these compounds took place. Radical mechanisms were proposed for the formation of simple amino acids, sugars, and nitrogen bases, i.e., the key structures of all living things, and also for the formation of oxygen. The calculation results confirm the possible important role of natural radioactivity in the evolution of terrestrial matter, and the emergence of life.

A liquid crystal world for the origins of life.

Nucleic acids (NAs) in modern biology accomplish a variety of tasks, and the emergence of primitive nucleic acids is broadly recognized as a crucial step for the emergence of life. While modern NAs have been optimized by evolution to accomplish various biological functions, such as catalysis or transmission of genetic information, primitive NAs could have emerged and been selected based on more rudimental chemical-physical properties, such as their propensity to self-assemble into supramolecular structures. One such supramolecular structure available to primitive NAs are liquid crystal (LC) phases, which are the outcome of the collective behavior of short DNA or RNA oligomers or monomers that self-assemble into linear aggregates by combinations of pairing and stacking. Formation of NA LCs could have provided many essential advantages for a primitive evolving system, including the selection of potential genetic polymers based on structure, protection by compartmentalization, elongation, and recombination by enhanced abiotic ligation. Here, we review recent studies on NA LC assembly, structure, and functions with potential prebiotic relevance. Finally, we discuss environmental or geological conditions on early Earth that could have promoted (or inhibited) primitive NA LC formation and highlight future investigation axes essential to further understanding of how LCs could have contributed to the emergence of life.

Life on Minerals: Binding Behaviors of Oligonucleotides on Zirconium Silicate and Its Inhibitory Activity for the Self-Cleavage of Hammerhead Ribozyme.

The role of minerals in the chemical evolution of RNA molecules is an important issue when considering the early stage of the Hadean Earth. In particular, the interaction between functional ribozymes and ancient minerals under simulated primitive conditions is a recent research focus. We are currently attempting to design a primitive RNA metabolic network which would function with minerals, and believe that the simulated chemical network of RNA molecules would be useful for evaluation of the chemical evolution from a simple RNA mixture to an RNA-based life-like system. First, we measured the binding interactions of oligonucleotides with four types of minerals; Aerosil silica, zirconium silicate, sepiolite, and montmorillonite. Oligonucleotides bound zirconium silicate and montmorillonite in the presence of MgCl2, and bound sepiolite both in the presence and absence of MgCl2, but they did not bind Aerosil. Based on the binding behavior, we attempted the self-cleavage reaction of the hammerhead ribozyme from an avocado viroid. This reaction was strongly inhibited by zirconium silicate, a compound regarded as mineral evidence for the existence of water. The present study suggests that the chemical evolution of functional RNA molecules requires specific conformational binding, resulting in efficient ribozyme function as well as zirconium silicate for the chemical evolution of biomolecules.

Autocatalytic Sets Arising in a Combinatorial Model of Chemical Evolution.

The idea that chemical evolution led to the origin of life is not new, but still leaves open the question of how exactly it could have led to a coherent and self-reproducing collective of molecules. One possible answer to this question was proposed in the form of the emergence of an autocatalytic set: a collection of molecules that mutually catalyze each other's formation and that is self-sustaining given some basic "food" source. Building on previous work, here we investigate in more detail when and how autocatalytic sets can arise in a simple model of chemical evolution based on the idea of combinatorial innovation with random catalysis assignments. We derive theoretical results, and compare them with computer simulations. These results could suggest a possible step towards the (or an) origin of life.

Stability of DL-Glyceraldehyde under Simulated Hydrothermal Conditions: Synthesis of Sugar-like Compounds in an Iron(III)-Oxide-Hydroxide-Rich Environment under Acidic Conditions.

Researchers have suggested that the condensation of low-molecular-weight aldehydes under basic conditions (e.g., pH > 11) is the prebiotic reaction responsible for the abiotic formation of carbohydrates. It has also been suggested that surface hydrothermal systems were ubiquitous during the early Archean period. Therefore, the catalysis of prebiotic carbohydrate synthesis by metallic oxide minerals under acidic conditions in these environments seems considerably more probable than the more widely hypothesized reaction routes. This study investigates the stability of DL-glyceraldehyde and its reaction products under the simulated conditions of an Archean surface hydrothermal system. The Hveradalur geothermal area in Iceland was selected as an analog of such a system. HPLC-ESIMS, UV−Vis spectroscopy, Raman spectroscopy and XPS spectroscopy were used to analyze the reaction products. In hot (323 K) and acidic (pH 2) solutions under the presence of suspended iron(III) oxide hydroxide powder, DL-glyceraldehyde readily decomposes into low-molecular-weight compounds and transforms into sugar-like molecules via condensation reactions.