The early metabolism arising in a Thioester world gave rise to amino acids and their simple peptides. The catalytic activity of these early simple peptides became instrumental in the transition from Thioester World to a Phosphate World. This transition involved the appearances of sugar phosphates, nucleotides, and polynucleotides. The coupling of the amino acids and peptides to nucleotides and polynucleotides is the origin for the genetic code. Many of the key steps in this transition are seen in the catalytic cores of the nucleotidyltransferases, the class II tRNA synthetases (aaRSs) and the CCA adding enzyme. These catalytic cores are dominated by simple beta hairpin structures formed in the Thioester World. The code evolved from a proto-tRNA, a tetramer XCCA interacting with a proto-aminoacyl-tRNA synthetase (aaRS) activating Glycine and Proline. The initial expanded code is found in the acceptor arm of the tRNA, the operational code. It is the coevolution of the tRNA with the aaRSs that is at the heart of the origin and evolution of the genetic code. There is also a close relationship between the accretion models of the evolving tRNA and that of the ribosome. Full article

Polymerization of nucleotides under prebiotically plausible conditions has been a focus of several origins of life studies. Non-activated nucleotides have been shown to undergo polymerization under geothermal conditions when subjected to dry-wet cycles. They do so by a mechanism similar to acid-catalyzed ester-bond formation. However, one study showed that the low pH of these reactions resulted in predominantly depurination, thereby resulting in the formation of abasic sites in the oligomers. In this study, we aimed to systematically characterize the nature of the oligomers that resulted in reactions that involved one or more of the canonical ribonucleotides. All the reactions analyzed showed the presence of abasic oligomers, with purine nucleotides being affected the most due to deglycosylation. Even in the reactions that contained nucleotide mixtures, the presence of abasic oligomers was detected, which suggested that information transfer would be severely hampered due to losing the capacity to base pair via H-bonds. Importantly, the stability of the N-glycosidic linkage, under conditions used for dry-wet cycling, was also determined. Results from this study further strengthen the hypothesis that chemical evolution in a pre-RNA World would have been vital for the evolution of informational molecules of an RNA World. This is evident in the high degree of instability displayed by N-glycosidic bonds of canonical purine ribonucleotides under the same geothermal conditions that otherwise readily favors polymerization. Significantly, the resultant product characterization in the reactions concerned underscores the difficulty associated with analyzing complex prebiotically relevant reactions due to inherent limitation of current analytical methods. Full article

Monosaccharides represent one of the major building blocks of life. One of the plausible prebiotic synthesis routes is the formose network, which generates sugars from C1 and C2 carbon sources in basic aqueous solution. We report on the feasibility of the formation of monosaccharides under physical forces simulated in a ball mill starting from formaldehyde, glycolaldehyde, DL-glyceraldehyde as prebiotically available substrates using catalytically active, basic minerals. We investigated the influence of the mechanic energy input on our model system using calcium hydroxide in an oscillatory ball mill. We show that the synthesis of monosaccharides is kinetically accelerated under mechanochemical conditions. The resulting sugar mixture contains monosaccharides with straight and branched carbon chains as well as decomposition products. In comparison to the sugar formation in water, the monosaccharides formed under mechanochemical conditions are more stable and selectively synthesized. Our results imply the possibility of a prebiotic monosaccharide origin in geochemical environments scant or devoid of water promoted by mechanochemical forces such as meteorite impacts or lithospheric activity. Full article

The catalytic effects of complex minerals or meteorites are often mentioned as important factors for the origins of life. To assess the possible role of nanoconfinement within a catalyst consisting of montmorillonite (MMT) and the impact of local electric field on the formation efficiency of the simple hypothetical precursors of nucleic acid bases or amino acids, we performed ab initio Car–Parrinello molecular dynamics simulations. We prepared four condensed-phase systems corresponding to previously suggested prototypes of a primordial soup. We monitored possible chemical reactions occurring within gas-like bulk and MMT-confined four simulation boxes on a 20-ps time scale at 1 atm and 300 K, 400 K, and 600 K. Elevated temperatures did not affect the reactivity of the elementary components of the gas-like boxes considerably; however, the presence of the MMT nanoclay substantially increased the formation probability of new molecules. Approximately 20 different new compounds were found in boxes containing carbon monoxide or formaldehyde molecules. This observation and an analysis of the atom–atom radial distribution functions indicated that the presence of Ca²⁺ ions at the surface of the internal MMT cavities may be an important factor in the initial steps of the formation of complex molecules at the early stages of the Earth’s history. Full article

Phosphates are essential for modern metabolisms. A recent study reported a phosphate-free metabolic network and suggested that thioesters, rather than phosphates, could alleviate thermodynamic bottlenecks of network expansion. As a result, it was considered that a phosphorus-independent metabolism could exist before the phosphate-based genetic coding system. To explore the origin of phosphorus-dependent metabolism, the present study constructs a protometabolic network that contains phosphates prebiotically available using computational systems biology approaches. It is found that some primitive phosphorylated intermediates could greatly alleviate thermodynamic bottlenecks of network expansion. Moreover, the phosphorus-dependent metabolic network exhibits several ancient features. Taken together, it is concluded that phosphates played a role as important as that of thioesters during the origin and evolution of metabolism. Both phosphorus and sulfur are speculated to be critical to the origin of life. Full article

The production of complex molecules in ammonia–carbon dioxide ices is presumed to pass through species of formula H₃N:CO₂ with further addition of ammonia and carbon dioxide. One possible landmark, carbamic acid, H₂NCOOH, has been implicated among the products of warming and irradiation of such ices. Experimental study of the IR spectra of residues has suggested the presence of related species, including weakly bound 1:1 and 2:1 complexes of ammonia with carbon dioxide, zwitterionic carbamic acid, ammonium carbamate, and the dimer of carbamic acid. We computed the energetics and vibrational spectra of these species as well as the complex between ammonia and carbamic acid for gas and condensed phases. By means of a new spectrum-matching scoring between computed and observed vibrational spectra, we infer species that are most probably present. The leading candidates are ammonium carbamate, the carbamic acid–ammonia complex, and the carbamic acid dimer. Full article

The emergence of life in a prebiotic world is an enormous scientific question of paramount philosophical importance. Even when life (in any sense we can define it) can be observed and replicated in the laboratory, it is only an indication of one possible pathway for life emergence, and is by no means be a demonstration of how life really emerged. The best we can hope for is to indicate plausible chemical–physical conditions and mechanisms that might lead to self-organizing and autopoietic systems. Here we present a stochastic simulation, based on chemical reactions already observed in prebiotic environments, that might help in the design of new experiments. We will show how the definition of simple rules for the synthesis of random peptides may lead to the appearance of networks of autocatalytic cycles and the emergence of memory. Full article

Information is the currency of life, but the origin of prebiotic information remains a mystery. We propose transitional pathways from the cosmic building blocks of life to the complex prebiotic organic chemistry that led to the origin of information systems. The prebiotic information system, specifically the genetic code, is segregated, linear, and digital, and it appeared before the emergence of DNA. In the peptide/RNA world, lipid membranes randomly encapsulated amino acids, RNA, and peptide molecules, which are drawn from the prebiotic soup, to initiate a molecular symbiosis inside the protocells. This endosymbiosis led to the hierarchical emergence of several requisite components of the translation machine: transfer RNAs (tRNAs), aminoacyl-tRNA synthetase (aaRS), messenger RNAs (mRNAs), ribosomes, and various enzymes. When assembled in the right order, the translation machine created proteins, a process that transferred information from mRNAs to assemble amino acids into polypeptide chains. This was the beginning of the prebiotic information age. The origin of the genetic code is enigmatic; herein, we propose an evolutionary explanation: the demand for a wide range of protein enzymes over peptides in the prebiotic reactions was the main selective pressure for the origin of information-directed protein synthesis. The molecular basis of the genetic code manifests itself in the interaction of aaRS and their cognate tRNAs. In the beginning, aminoacylated ribozymes used amino acids as a cofactor with the help of bridge peptides as a process for selection between amino acids and their cognate codons/anticodons. This process selects amino acids and RNA species for the next steps. The ribozymes would give rise to pre-tRNA and the bridge peptides to pre-aaRS. Later, variants would appear and evolution would produce different but specific aaRS-tRNA-amino acid combinations. Pre-tRNA designed and built pre-mRNA for the storage of information regarding its cognate amino acid. Each pre-mRNA strand became the storage device for the genetic information that encoded the amino acid sequences in triplet nucleotides. As information appeared in the digital languages of the codon within pre-mRNA and mRNA, and the genetic code for protein synthesis evolved, the prebiotic chemistry then became more organized and directional with the emergence of the translation and genetic code. The genetic code developed in three stages that are coincident with the refinement of the translation machines: the GNC code that was developed by the pre-tRNA/pre-aaRS /pre-mRNA machine, SNS code by the tRNA/aaRS/mRNA machine, and finally the universal genetic code by the tRNA/aaRS/mRNA/ribosome machine. We suggest the coevolution of translation machines and the genetic code. The emergence of the translation machines was the beginning of the Darwinian evolution, an interplay between information and its supporting structure. Our hypothesis provides the logical and incremental steps for the origin of the programmed protein synthesis. In order to better understand the prebiotic information system, we converted letter codons into numerical codons in the Universal Genetic Code Table. We have developed a software, called CATI (Codon-Amino Acid-Translator-Imitator), to translate randomly chosen numerical codons into corresponding amino acids and vice versa. This conversion has granted us insight into how the genetic code might have evolved in the peptide/RNA world. There is great potential in the application of numerical codons to bioinformatics, such as barcoding, DNA mining, or DNA fingerprinting. We constructed the likely biochemical pathways for the origin of translation and the genetic code using the Model-View-Controller (MVC) software framework, and the translation machinery step-by-step. While using AnyLogic software, we were able to simulate and visualize the entire evolution of the translation machines, amino acids, and the genetic code. Full article

Extant life uses two kinds of linear biopolymers that mutually control their own production, as well as the cellular metabolism and the production and homeostatic maintenance of other biopolymers. Nucleic acids are linear polymers composed of a relatively low structural variety of monomeric residues, and thus a low diversity per accessed volume. Proteins are more compact linear polymers that dispose of a huge compositional diversity even at the monomeric level, and thus bear a much higher catalytic potential. The fine-grained diversity of proteins makes an unambiguous information transfer from protein templates too error-prone, so they need to be resynthesized in every generation. But proteins can catalyse both their own reproduction as well as the efficient and faithful replication of nucleic acids, which resolves in a most straightforward way an issue termed “Eigen’s paradox”. Here the importance of the existence of both kinds of linear biopolymers is discussed in the context of the emergence of cellular life, be it for the historic orgin of life on Earth, on some other habitable planet, or in the test tube. An immediate consequence of this analysis is the necessity for translation to appear early during the evolution of life. Full article

The alkaline-hydrothermal-vent theory for the origin of life predicts the spontaneous reduction of CO₂, dissolved in acidic ocean waters, with H₂ from the alkaline vent effluent. This reaction would be catalyzed by Fe(Ni)S clusters precipitated at the interface, which effectively separate the two fluids into an electrochemical cell. Using microfluidic reactors, we set out to test this concept. We produced thin, long Fe(Ni)S precipitates of less than 10 µm thickness. Mixing simplified analogs of the acidic-ocean and alkaline-vent fluids, we then tested for the reduction of CO₂. We were unable to detect reduced carbon products under a number of conditions. As all of our reactions were performed at atmospheric pressure, the lack of reduced carbon products may simply be attributable to the low concentration of hydrogen in our system, suggesting that high-pressure reactors may be a necessity. Full article

Life as we know it would not exist without the ability of protein sequences to bind metal ions. Transition metals, in particular, play essential roles in a wide range of structural and catalytic functions. The ubiquitous occurrence of metalloproteins in all organisms leads one to ask whether metal binding is an evolved trait that occurred only rarely in ancestral sequences, or alternatively, whether it is an innate property of amino acid sequences, occurring frequently in unevolved sequence space. To address this question, we studied 52 proteins from a combinatorial library of novel sequences designed to fold into 4-helix bundles. Although these sequences were neither designed nor evolved to bind metals, the majority of them have innate tendencies to bind the transition metals copper, cobalt, and zinc with high nanomolar to low-micromolar affinity. Full article

The Strecker reaction of aldehydes with ammonia and hydrogen cyanide first leads to α-aminonitriles, which are then hydrolyzed to α-amino acids. However, before reacting with water, these aminonitriles can be trapped by aminothiols, such as cysteine or homocysteine, to give 5- or 6-membered ring heterocycles, which in turn are hydrolyzed to dipeptides. We propose that this two-step process enabled the formation of thiol-containing dipeptides in the primitive ocean. These small peptides are able to promote the formation of other peptide bonds and of heterocyclic molecules. Theoretical calculations support our experimental results. They predict that α-aminonitriles should be more reactive than other nitriles, and that imidazoles should be formed from transiently formed amidinonitriles. Overall, this set of reactions delineates a possible early stage of the development of organic chemistry, hence of life, on Earth dominated by nitriles and thiol-rich peptides (TRP). Full article

The very specific thermodynamic instability and kinetic stability of phosphate esters and anhydrides impart them invaluable properties in living organisms in which highly efficient enzyme catalysts compensate for their low intrinsic reactivity. Considering their role in protein biosynthesis, these properties raise a paradox about early stages: How could these species be selected in the absence of enzymes? This review is aimed at demonstrating that considering mixed anhydrides or other species more reactive than esters and anhydrides can help in solving the paradox. The consequences of this approach for chemical evolution and early stages of life are analysed. Full article

Systems Chemistry has its roots in the research on the autocatalytic self-replication of biological macromolecules, first of all of synthetic deoxyribonucleic acids. A personal tour through the early works of the founder of Systems Chemistry, and of his first followers, recalls what’s most important in this new era of chemistry: the growth and evolution of compartmented macromolecular populations, when provided with “food” and “fuel” and disposed of “waste”. Full article

Understanding how life began is one of the most fascinating problems to solve. By approaching this enigma from a chemistry perspective, the goal is to define what series of chemical reactions could lead to the synthesis of nucleotides, amino acids, lipids, and other cellular components from simple feedstocks under prebiotically plausible conditions. It is well established that evolution of life involved RNA which plays central roles in both inheritance and catalysis. In this review, we present historically important and recently published articles aimed at understanding the emergence of RNA nucleosides and nucleotides on the early Earth. Full article

Molecular Darwinian evolution is an intrinsic property of reacting pools of molecules resulting in the adaptation of the system to changing conditions. It has no a priori aim. From the point of view of the origin of life, Darwinian selection behavior, when spontaneously emerging in the ensembles of molecules composing prebiotic pools, initiates subsequent evolution of increasingly complex and innovative chemical information. On the conservation side, it is a posteriori observed that numerous biological processes are based on prebiotically promptly made compounds, as proposed by the concept of Chemomimesis. Molecular Darwinian evolution and Chemomimesis are principles acting in balanced cooperation in the frame of Systems Chemistry. The one-pot synthesis of nucleosides in radical chemistry conditions is possibly a telling example of the operation of these principles. Other indications of similar cases of molecular evolution can be found among biogenic processes. Full article

A mixture of sugar diphosphates is produced in reactions between small aldehyde phosphates catalysed by layered double hydroxide (LDH) clays under plausibly prebiotic conditions. A subset of these, pentose diphosphates, constitute the backbone subunits of nucleic acids capable of base pairing, which is not the case for the other products of these LDH-catalysed reactions. Not only that, but to date no other polymer found capable of base pairing—and therefore information transfer—has a backbone for which its monomer subunits have a plausible prebiotic synthesis, including the ribose-5-phosphate backbone subunit of RNA. Pentose diphosphates comprise the backbone monomers of pentopyranose nucleic acids, some of the strongest base pairing systems so far discovered. We have previously proposed that the first base pairing interactions were between purine nucleobase precursors, and that these were weaker and less specific than standard purine-pyrimidine interactions. We now propose that the inherently stronger pairing of pentopyranose nucleic acids would have compensated for these weaker interactions, and produced an informational polymer capable of undergoing nonenzymatic replication. LDH clays might also have catalysed the synthesis of the purine nucleobase precursors, and the polymerization of pentopyranose nucleotide monomers into oligonucleotides, as well as the formation of the first lipid bilayers. Full article