Life — Open Access Journal of Origins and Evolution of Life

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

Minerals might have played critical roles for the origin and evolution of possible life forms on Mars. The study of the interactions between the “building blocks of life” and minerals relevant to Mars mineralogy under conditions mimicking the harsh Martian environment may provide key insight into possible prebiotic processes. Therefore, this contribution aims at reviewing the most important investigations carried out so far about the catalytic/protective properties of Martian minerals toward molecular biosignatures under Martian-like conditions. Overall, it turns out that the fate of molecular biosignatures on Mars depends on a delicate balance between multiple preservation and degradation mechanisms, often regulated by minerals, which may take place simultaneously. Such a complexity requires more efforts in simulating realistically the Martian environment in order to better inspect plausible prebiotic pathways and shed light on the nature of the organic compounds detected both in meteorites and on the surface of Mars through in situ analysis. Full article

How life began on Earth is still largely shrouded in mystery. One of the central ideas for various origins of life scenarios is Darwin’s “warm little pond”. In these small bodies of water, simple prebiotic compounds such as amino acids, nucleobases, and so on, were produced from reagents such as hydrogen cyanide and aldehydes/ketones. These simple prebiotic compounds underwent further reactions, producing more complex molecules. The process of chemical evolution would have produced increasingly complex molecules, eventually yielding a molecule with the properties of information storage and replication prone to random mutations, the hallmark of both the origin of life and evolution. However, there is one problematic issue with this scenario: On the Earth >3.5 Gyr ago there would have likely been no exposed continental crust above sea level. The only land areas that protruded out of the oceans would have been associated with hotspot volcanic islands, such as the Hawaiian island chain today. On these long-lived islands, in association with reduced gas-rich eruptions accompanied by intense volcanic lightning, prebiotic reagents would have been produced that accumulated in warm or cool little ponds and lakes on the volcano flanks. During seasonal wet–dry cycles, molecules with increasing complexity could have been produced. These islands would have thus been the most likely places for chemical evolution and the processes associated with the origin of life. The islands would eventually be eroded away and their chemical evolution products would have been released into the oceans where Darwinian evolution ultimately produced the biochemistry associated with all life on Earth today. Full article

Membrane proteins are important drug targets which play a pivotal role in various cellular activities. However, unlike cytosolic proteins, most of them are difficult-to-express proteins. In this study, to synthesize and produce sufficient quantities of membrane proteins for functional and structural analysis, we used a bottom-up approach in a reconstituted cell-free synthesis system, the PURE system, supplemented with artificial lipid mimetics or micelles. Membrane proteins were synthesized by the cell-free system and integrated into lipid bilayers co-translationally. Membrane proteins such as the G-protein coupled receptors were expressed in the PURE system and a productivity ranging from 0.04 to 0.1 mg per mL of reaction was achieved with a correct secondary structure as predicted by circular dichroism spectrum. In addition, a ligand binding constant of 27.8 nM in lipid nanodisc and 39.4 nM in micelle was obtained by surface plasmon resonance and the membrane protein localization was confirmed by confocal microscopy in giant unilamellar vesicles. We found that our method is a promising approach to study the different classes of membrane proteins in their native-like artificial lipid bilayer environment for functional and structural studies. Full article

Experimental evolution in chemical models of cells could reveal the fundamental mechanisms of cells today. Various chemical cell models, water-in-oil emulsions, oil-on-water droplets, and vesicles have been constructed in order to conduct research on experimental evolution. In this review, firstly, recent studies with these candidate models are introduced and discussed with regards to the two hierarchical directions of experimental evolution (chemical evolution and evolution of a molecular self-assembly). Secondly, we suggest giant vesicles (GVs), which have diameters larger than 1 µm, as promising chemical cell models for studying experimental evolution. Thirdly, since technical difficulties still exist in conventional GV experiments, recent developments of microfluidic devices to deal with GVs are reviewed with regards to the realization of open-ended evolution in GVs. Finally, as a future perspective, we link the concept of messy chemistry to the promising, unexplored direction of experimental evolution in GVs. Full article

Glutamine synthetase (GS) features prominently in bacterial nitrogen assimilation as it catalyzes the entry of bioavailable nitrogen in form of ammonium into cellular metabolism. The classic example, the comprehensively characterized GS of enterobacteria, is subject to exquisite regulation at multiple levels, among them gene expression regulation to control GS abundance, as well as feedback inhibition and covalent modifications to control enzyme activity. Intriguingly, the GS of the ecologically important clade of cyanobacteria features fundamentally different regulatory systems to those of most prokaryotes. These include the interaction with small proteins, the so-called inactivating factors (IFs) that inhibit GS linearly with their abundance. In addition to this protein interaction-based regulation of GS activity, cyanobacteria use alternative elements to control the synthesis of GS and IFs at the transcriptional level. Moreover, cyanobacteria evolved unique RNA-based regulatory mechanisms such as glutamine riboswitches to tightly tune IF abundance. In this review, we aim to outline the current knowledge on the distinctive features of the cyanobacterial GS encompassing the overall control of its activity, sensing the nitrogen status, transcriptional and post-transcriptional regulation, as well as strain-specific differences. Full article

2-oxoglutarate (α-ketoglutarate; 2-OG) is an intermediate of the Krebs cycle, and constitutes the carbon skeleton for nitrogen assimilation and the synthesis of a variety of compounds. In addition to being an important metabolite, 2-OG is a signaling molecule with a broad regulatory repertoire in a variety of organisms, including plants, animals, and bacteria. Although challenging, measuring the levels and variations of metabolic signals in vivo is critical to better understand how cells control specific processes. To measure cellular 2-OG concentrations and dynamics, we designed a set of biosensors based on the fluorescence resonance energy transfer (FRET) technology that can be used in vivo in different organisms. For this purpose, we took advantage of the conformational changes of two cyanobacterial proteins induced by 2-OG binding. We show that these biosensors responded immediately and specifically to different 2-OG levels, and hence allowed to measure 2-OG variations in function of environmental modifications in the proteobacterium Escherichia coli and in the cyanobacterium Anabaena sp. PCC 7120. Our results pave the way to study 2-OG dynamics at the cellular level in uni- and multi-cellular organisms. Full article

We characterized the adsorption of triglycine molecules on a pyrite surface under several simulated environmental conditions by X-ray photoemission spectroscopy. The triglycine molecular adsorption on a pyrite surface under vacuum conditions (absence of oxygen) shows the presence of two different states for the amine functional group (NH₂ and NH₃⁺), therefore two chemical species (anionic and zwitterionic). On the other hand, molecular adsorption from a solution discriminates the NH₂ as a unique molecular adsorption form, however, the amount adsorbed in this case is higher than under vacuum conditions. Furthermore, molecular adsorption on the mineral surface is even favored if the pyrite surface has been irradiated before the molecular adsorption occurs. Pyrite surface chemistry is highly sensitive to the chemical changes induced by UV irradiation, as XPS analysis shows the presence of Fe₂O₃ and Fe₂SO₄—like environments on the surface. Surface chemical changes induced by UV help to increase the probability of adsorption of molecular species and their subsequent concentration on the pyrite surface. Full article

Studies that measured mutation rates in human populations using pedigrees have reported values that differ significantly from rates estimated from the phylogenetic comparison of humans and chimpanzees. Consequently, exchanges between mutation rate values across different timescales lead to conflicting divergence time estimates. It has been argued that this variation of mutation rate estimates across hominoid evolution is in part caused by incorrect assignment of calibration information to the mean coalescent time among loci, instead of the true genetic isolation (speciation) time between humans and chimpanzees. In this study, we investigated the feasibility of estimating the human pedigree mutation rate using phylogenetic data from the genomes of great apes. We found that, when calibration information was correctly assigned to the human–chimpanzee speciation time (and not to the coalescent time), estimates of phylogenetic mutation rates were statistically equivalent to the estimates previously reported using studies of human pedigrees. We conclude that, within the range of biologically realistic ancestral generation times, part of the difference between whole-genome phylogenetic and pedigree mutation rates is due to inappropriate assignment of fossil calibration information to the mean coalescent time instead of the speciation time. Although our results focus on the human–chimpanzee divergence, our findings are general, and relevant to the inference of the timescale of the tree of life. 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

Prebiotic organic synthesis catalyzed by Earth-abundant metal sulfides is a key process for understanding the evolution of biochemistry from inorganic molecules, yet the catalytic functions of sulfides have remained poorly explored in the context of the origin of life. Past studies on prebiotic chemistry have mostly focused on a few types of metal sulfide catalysts, such as FeS or NiS, which form limited types of products with inferior activity and selectivity. To explore the potential of metal sulfides on catalyzing prebiotic chemical reactions, here, the chemical diversity (variations in chemical composition and phase structure) of 304 natural metal sulfide minerals in a mineralogy database was surveyed. Approaches to rationally predict the catalytic functions of metal sulfides are discussed based on advanced theories and analytical tools of electrocatalysis such as proton-coupled electron transfer, structural comparisons between enzymes and minerals, and in situ spectroscopy. To this end, we introduce a model of geoelectrochemistry driven prebiotic synthesis for chemical evolution, as it helps us to predict kinetics and selectivity of targeted prebiotic chemistry under “chemically messy conditions”. We expect that combining the data-mining of mineral databases with experimental methods, theories, and machine-learning approaches developed in the field of electrocatalysis will facilitate the prediction and verification of catalytic performance under a wide range of pH and Eh conditions, and will aid in the rational screening of mineral catalysts involved in the origin of life. Full article

Long term human missions to the Moon and Mars, rely on life support systems for food production and regeneration of resources. In the EU H2020 TIME SCALE-project, an advanced life support system concept was developed to facilitate plant research and technology demonstration under different gravity conditions. Ground experiments assessed irrigation systems and effects of rooting- and nutrient solution volume. The maximal allowed volume for existing International Space Station research facilities (3.4 L) was able to support cultivation of two lettuce heads for at least 24 days. A smaller rooting volume (0.6 L) increased root biomass after 24 days, but induced a 5% reduction in total biomass at day 35. Regulating effects of nitrate supply on plant water fluxes in light and dark were also investigated. At low concentrations of nitrate in the nutrient solution, both transpiration and stomatal conductance increased rapidly with increasing nitrate concentration. During day-time this increase levelled off at high concentrations, while during nigh-time there was a distinct decline at supra optimal concentrations. Plants supplied with nitrate concentrations as low as 1.25 mM did not show visible signs of nutrient stress or growth reduction. These findings hold promise for both reducing the environmental impact of terrestrial horticulture and avoiding nutrient stress in small scale closed cultivation systems for space. Full article

One of the most intriguing questions in biological science is how life originated on Earth. A large number of hypotheses have been proposed to explain it, each putting an emphasis on different events leading to functional translation and self-sustained system. Here, we propose a set of interactions that could have taken place in the prebiotic environment. According to our hypothesis, hybridization-induced proximity of short aminoacylated RNAs led to the synthesis of peptides of random sequence. We postulate that among these emerged a type of peptide(s) capable of stimulating the interaction between specific RNAs and specific amino acids, which we call “bridge peptide” (BP). We conclude that translation should have emerged at the same time when the standard genetic code begun to evolve due to the stabilizing effect on RNA-peptide complexes with the help of BPs. Ribosomes, ribozymes, and the enzyme-directed RNA replication could co-evolve within the same period, as logical outcome of RNA-peptide world without the need of RNA only self-sustained step. Full article

Propagation of genetic information is a fundamental prerequisite for living cells. We recently developed the replication cycle reaction (RCR), an in vitro reaction for circular DNA propagation, by reconstitution of the replication cycle of the Escherichia coli chromosome. In RCR, two replication forks proceed bidirectionally from the replication origin, oriC, and meet at a region opposite oriC, yielding two copies of circular DNA. Although RCR essentially propagates supercoiled monomers, concatemer byproducts are also produced due to inefficient termination of the replication fork progression. Here, we examined the effect of the Tus-ter replication fork trap in RCR. Unexpectedly, when the fork traps were placed opposite oriC, mimicking their arrangement on the chromosome, the propagation of circular DNA was inhibited. On the other hand, fork traps flanking oriC allowed efficient propagation of circular DNA and repressed concatemer production. These findings suggest that collision of the two convergence forks through the fork trap is detrimental to repetition of the replication cycle. We further demonstrate that this detrimental effect was rescued by the UvrD helicase. These results provide insights into the way in which circular DNA monomers replicate repetitively without generating concatemers. Full article

Mineral surfaces have been demonstrated to play a central role in prebiotic reactions, which are understood to be at the basis of the origin of life. Among the various molecules proposed as precursors for these reactions, one of the most interesting is formamide. Formamide has been shown to be a pluripotent molecule, generating a wide distribution of relevant prebiotic products. In particular, the outcomes of its reactivity are strongly related to the presence of mineral phases acting as catalysts toward specific reaction pathways. While the mineral–products relationship has been deeply studied for a large pool of materials, the fundamental description of formamide reactivity over mineral surfaces at a microscopic level is missing in the literature. In particular, a key step of formamide chemistry at surfaces is adsorption on available interaction sites. This report aims to investigate the adsorption of formamide over a well-defined amorphous silica, chosen as a model mineral surface. An experimental IR investigation of formamide adsorption was carried out and its outcomes were interpreted on the basis of first principles simulation of the process, adopting a realistic model of amorphous silica. Full article

Rock–water–carbon interactions germane to serpentinization in hydrothermal vents have occurred for over 4 billion years, ever since there was liquid water on Earth. Serpentinization converts iron(II) containing minerals and water to magnetite (Fe₃O₄) plus H₂. The hydrogen can generate native metals such as awaruite (Ni₃Fe), a common serpentinization product. Awaruite catalyzes the synthesis of methane from H₂ and CO₂ under hydrothermal conditions. Native iron and nickel catalyze the synthesis of formate, methanol, acetate, and pyruvate—intermediates of the acetyl-CoA pathway, the most ancient pathway of CO₂ fixation. Carbon monoxide dehydrogenase (CODH) is central to the pathway and employs Ni⁰ in its catalytic mechanism. CODH has been conserved during 4 billion years of evolution as a relic of the natural CO₂-reducing catalyst at the onset of biochemistry. The carbide-containing active site of nitrogenase—the only enzyme on Earth that reduces N₂—is probably also a relic, a biological reconstruction of the naturally occurring inorganic catalyst that generated primordial organic nitrogen. Serpentinization generates Fe₃O₄ and H₂, the catalyst and reductant for industrial CO₂ hydrogenation and for N₂ reduction via the Haber–Bosch process. In both industrial processes, an Fe₃O₄ catalyst is matured via H₂-dependent reduction to generate Fe₅C₂ and Fe₂N respectively. Whether serpentinization entails similar catalyst maturation is not known. We suggest that at the onset of life, essential reactions leading to reduced carbon and reduced nitrogen occurred with catalysts that were synthesized during the serpentinization process, connecting the chemistry of life and Earth to industrial chemistry in unexpected ways. Full article

In recent years, there has been a large increase in the amount of experimental evidence for diverse archaeal organisms, and these findings allow for a comprehensive analysis of archaeal genetic organization. However, studies about regulatory mechanisms in this cellular domain are still limited. In this context, we identified a repertoire of 86 DNA-binding transcription factors (TFs) in the archaeon Pyrococcus furiosus DSM 3638, that are clustered into 32 evolutionary families. In structural terms, 45% of these proteins are composed of one structural domain, 41% have two domains, and 14% have three structural domains. The most abundant DNA-binding domain corresponds to the winged helix-turn-helix domain; with few alternative DNA-binding domains. We also identified seven regulons, which represent 13.5% (279 genes) of the total genes in this archaeon. These analyses increase our knowledge about gene regulation in P. furiosus DSM 3638 and provide additional clues for comprehensive modeling of transcriptional regulatory networks in the Archaea cellular domain. Full article

In 2001, the first author (S.N.) led the publication of a book entitled “Geochemistry and the origin of life” in collaboration with Dr. Andre Brack aiming to figure out geo- and astro-chemical processes essential for the emergence of life. Since then, a great number of research progress has been achieved in the relevant topics from our group and others, ranging from the extraterrestrial inputs of life’s building blocks, the chemical evolution on Earth with the aid of mineral catalysts, to the fossilized records of ancient microorganisms. Here, in addition to summarizing these findings for the origin and early evolution of life, we propose a new hypothesis for the generation and co-evolution of photosynthesis with the redox and photochemical conditions on the Earth’s surface. Besides these bottom-up approaches, we introduce an experimental study on the role of water molecules in the life’s function, focusing on the transition from live, dormant, and dead states through dehydration/hydration. Further spectroscopic studies on the hydrogen bonding behaviors of water molecules in living cells will provide important clues to solve the complex nature of life. Full article