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Fact and assumption in studies on the origins of life.

Proteins and nucleic acids organise metabolic systems very efficiently. Original forms of life may have depended on less efficient mechanisms which have been superseded in the course of evolutionary selection. Discussion and experiment on the origins of life should therefore not depend on the assumption that substances and mechanisms, now seemingly essential, were essential initially. Instead we should consider what might happen in a few million years on moist mineral surfaces, smeared with bituminous material, and exposed to UV light in a reducing atmosphere in the absence of predators. What little evidence can be gathered from differences in composition and metabolic behaviour between ancient and recently evolved species suggests that the trend in biochemical evolution is towards simplification.

Animals↗

An RNA Condensate Model for the Origin of Life.

The RNA World hypothesis predicts that self-replicating RNAs evolved before DNA genomes and coded proteins. Despite widespread support for the RNA World, self-replicating RNAs have yet to be identified in a natural context, leaving a key 'missing link' for this explanation of the origin of life. Inspired by recent work showing that condensates of charged polymers are capable of catalyzing chemical reactions, we consider a catalytic RNA condensate as a candidate for the self-replicating RNA. Specifically, we propose that short, low-complexity RNA polymers formed catalytic condensates capable of templated RNA polymerization. Because the condensate properties depend on the RNA sequences, RNAs that formed condensates with improved polymerization and demixing capacity would be amplified, leading to a 'condensate chain reaction' and evolution by natural selection. Many of the needed properties of this self-replicating RNA condensate have been realized experimentally in recent studies and our predictions could be tested with current experimental and theoretical tools. Our theory addresses central problems in the origins of life: (i) the origin of compartmentalization, (ii) the error threshold for the accuracy of templated replication, (iii) the free energy cost of maintaining an information-rich population of replicating RNA polymers. Furthermore, we note that the extant nucleolus appears to satisfy many of the requirements of an evolutionary relic for the model we propose. More generally, we suggest that future work on the origin of life would benefit from condensate-centric biophysical models of RNA evolution.

Origin of Life↗

Montmorillonite-catalysed formation of RNA oligomers: the possible role of catalysis in the origins of life.

Large deposits of montmorillonite are present on the Earth today and it is believed to have been present at the time of the origin of life and has recently been detected on Mars. It is formed by aqueous weathering of volcanic ash. It catalyses the formation of oligomers of RNA that contain monomer units from 2 to 30-50. Oligomers of this length are formed because this catalyst controls the structure of the oligomers formed and does not generate all possible isomers. Evidence of sequence-, regio- and homochiral selectivity in these oligomers has been obtained. Postulates on the role of selective versus specific catalysts on the origins of life are discussed. An introduction to the origin of life is given with an emphasis on reaction conditions based on the recent data obtained from zircons 4.0-4.5Ga.

Amino Acids↗

The place of metabolism in the origin of life.

Metabolism and replication are generally considered essential features of biological life. Workers in the field of the origin of life are mostly split into two groups, depending on which of these two functions is postulated to have occurred first. Because of difficulties encountered by the replication-first (or genetics-first) approach, some workers have postulated that a highly developed metabolism must have originated before replication and the formation of a genetic apparatus. However, as supporters of a replication-first approach have pointed out, and as is discussed in this article, the alternative metabolism-first approach has fundamental problems that have not been sufficiently addressed.

DNA↗

Deterministic hypotheses on the origin of life and of its reproduction.

The current theory of the origin of life by random polymerisation and selection of nucleic acids is challenged by the hypothesis that the primitive enzymatic sites would have been formed by abiotic polymerisation of aminoacids, specifically gathered (by saline, hydrogen, or hydrophobic interactions), around the different substrates. The information contained in these proteinoids would have been transferred to messenger-like RNAs by a mechanism reverse of that of the present protein synthesis, and then to DNA. The interactions between aminoacids and nucleotidic sequences would have been at the origin of the genetic code, as hypothesized by several authors. We propose that the specificity of the bindings would have been enhanced and 'frozen' by ternary associations with specific proteinoids (future aminoacyl tRNA synthetases). The role of chance would have been limited to the supply of the products and to the determination of the conditions of reaction. Thermodynamic considerations (dissipation of the free enthalpy through enzymatic activities) may explain the emergence of the biological systems.

Binding Sites↗

Common structural features of replication origins in all life forms.

Origins of replication (ORIs) among prokaryotes, viruses, and multicellular organisms appear to possess simple tri-, tetra-, or higher dispersed repetitions of nucleotides, AT tracts, inverted repeats, one to four binding sites of an initiator protein, intrinsically curved DNA, DNase I-hypersensitive sites, a distinct pattern of DNA methylation, and binding sites for transcription factors. Eukaryotic ORIs are sequestered on the nuclear matrix; this attachment is supposed to facilitate execution of their activation/deactivation programs during development. Furthermore, ORIs fall into various classes with respect to their sequence complexity: those enriched in AT tracts, those with GA- and CT-rich tracts, a smaller class of GC-rich ORIs, and a major class composed of mixed motifs yet containing distinct AT and polypurine or GC stretches. Multimers of an initiator protein in prokaryotes and viruses that might have evolved into a multiprotein replication initiation complex in multicellular organisms bind to the core ORI, causing a structural distortion to the DNA which is transferred to the AT tract flanking the initiator protein site; single-stranded DNA-binding proteins then interact with the melted AT tract as well as with the DNA polymerase alpha-primase complex in animal viruses and mammalian cells, causing initiation in DNA replication. ORIs in mammalian cells seem to colocalize with matrix-attached regions and are proposed to become DNase I-hypersensitive during their activation.

Animals↗

The role of accuracy for early stages of the origin of life.

The role of accuracy in developing stages in the origin of life is investigated by mathematical models. Errors yield difficult stability problems in a description of a cooperative system with information-carriers (genes) and catalytic polymers (enzymes) that are related to each other. This problem is highly relevant for a proper understanding of the RNA world. The model that is treated takes two relevant error effects, which can be coupled, into account. One is the occurrence of parasites, inactive genes that are efficiently reproduced by the catalytic support of other polymers but which do not give rise to any catalytic activity. The other is an error propagation due to the fact that erroneous catalysts will provide an increased error level and thus more erroneous catalysts which may lead to still increasing error levels, eventually an error catastrophe.

Evolution, Chemical↗

A research proposal on the origin of life.

This paper describes some experiments the author would have liked to carry out if he had started earlier in the origin-of-life field. The proposal is preceded by a hypothetical outline of the main events in the origin of life. According to this outline, the emergence of life amounts to the transition between two kinds of chemistry: 1) cosmic chemistry, which is beginning to be understood and most likely provided the building blocks with which life was first constructed; and 2) biochemistry, the well-known set of enzyme-catalyzed metabolic reactions that support all living organisms today and must have supported the universal common ancestor, or LUCA, from which all known forms of life are derived. The pathway leading from one to the other of those two chemistries may be divided into three stages, defined as the pre-RNA, RNA, and protein-DNA stages. A brief summary of the events that may have occurred in these three stages and of the possible underlying mechanisms is given. It is emphasized that these events were chemical in nature and, especially, that they must have prefigured present-day biochemical processes. Protometabolism and metabolism, it is argued, must have been congruent. With congruence as the underlying working hypothesis, three problems open to experimental investigation are considered: 1) the involvement of peptides and other multimers as catalysts of early biogenic chemistry; 2) the participation of thioesters in primitive energy transactions; and 3) the influence of amino acids on the molecular selection of RNA molecules.

Amino Acids↗

Chemical evolution and the origin of life: cumulative keyword subject index 1970-1986.

This cumulative subject index encompasses the subject indexes of the bibliographies on Chemical Evolution and the Origin of Life that were first published in 1970 and have continued through publication of the 1986 bibliography supplement. Early bibliographies focused on experimental and theoretical material dealing directly with the concepts of chemical evolution and the origin of life, excluding the broader areas of exobiology, biological evolution, and geochemistry. In recent years, these broader subject areas have also been incorporated as they appear in literature searches relating to chemical evolution and the origin of life, although direct attempts have not been made to compile all of the citations in these broad areas. The keyword subject indexes have also undergone an analogous change in scope. Compilers of earlier bibliographies used the most specific term available in producing the subject index. Compilers of recent bibliographies have used a number of broad terms relating to the overall subject content of each citation and specific terms where appropriate. The subject indexes of these 17 bibliographies have, in general, been cumulatively compiled exactly as they originally appeared. However, some changes have been made in an attempt to correct errors, combine terms, and provide more meaningful terms.

Exobiology↗

Hydrothermal and oceanic pH conditions of possible relevance to the origin of life.

Because of the continuous focusing of thermal and chemical energy, ancient submarine hot springs are contenders as sites for the origin of life. But it is generally assumed that these would be of the acid and high-temperature 'black smoker' variety (Corliss et al., 1981). In fact today the greater part of the ocean circulates through off-ridge springs where it issues after modification at temperatures of around 40 degrees C or so but with the potential to reach 200 degrees C. Such offridge or ridge-flank springs remind us that there are other candidate sites for the origin of life. Although there is no firm indication of the pH of these off-ridge springs we have argued that the solutions are likely to be alkaline rather than acid, We test the feasibility of this idea using EQ geochemical water-rock interaction modelling codes (Wolery 1983) and find that for a range of possible initial chemistries of Hadean seawater, the pH of issuing solutions at around 200 degrees C is around one or more units alkaline. Such pH values hold for interaction with both basaltic and komatiitic crust. The robustness of this result suggests to us that alkaline submarine springs of moderate temperature, carrying many hundreds of ppm HS to the ocean basins, are also serious contenders as sites for the origin of life, particularly as Hadean seawater was probably slightly acid, with a dissolved iron concentration approaching 100 ppm. On mixing of these solutions, supersaturation, especially of iron sulphide, would lead to the precipitation of colloidal gels. In our view iron sulphide was the likely substance of, or contributor to, the first vesicle membranes which led to life, as the supply organic molecules would have been limited in the Hadean. Such a membrane would have bid catalytic properties, expansivity, and would have maintained the natural chemiosmotic gradient, a consequence of the acid ocean and the alkaline interior to the vesicles.

Evolution, Planetary↗

A hypothesis on the role of pressure in the origin of life.

The necessity for long time spans in models on the origin of life leads to a major difficulty in that under the environmental conditions existing today biological macromolecules are inherently unstable. The present hypothesis suggests that life arose under a set of environmental conditions whereby polymerization was thermodynamically favored. In particular, increased pressure when coupled with low water activity and high temperature should stabilize polymer bond formation. Three implications of this pressure stabilization theory are presented: (1) The necessary conditions for stabilization are similar to some of the ecological niches occupied by representatives of the archaebacteria. It is suggested that the harsh and unusual habitats of the archaebacteria reflect in part prebiotic environmental conditions. (2) Biological optical activity would be generated if, for instance, L-L peptide bonds were stabilized to a greater degree than L-D peptide bonds. This type of selective stabilization would provide for the maintenance of molecular asymmetry as well as the creation of molecular asymmetry. (3) Conditions necessary for generating the requisite pressure may concurrently have provided protection from prebiotic ultraviolet radiation.

Archaea↗

A fission-fusion origin for life.

To develop a comprehensive 'cells-first' approach to the origin of life, we propose that protocells form spontaneously and that the fission and fusion of these protocells drives the dynamics of their evolution. The fitness criterion for this evolution is taken to be the the stability (conservation) of domains in the protocellular membrane as determined by non-covalent molecular associations between the amphiphiles of the membrane and a subset of the macromolecules in the protocell. In the presence of a source of free energy the macromolecular content of the protocell (co-)evolves as the result of (domain-dependent) membrane-catalysed polymerisation of the prebiotic constituents delivered to the protocell by fusion. The metabolism of the cell therefore (co-)evolves on a rugged fitness landscape. We indicate how domain evolution with the same fitness criterion can potentially give rise to coding. Membrane domains may therefore provide the link between protocells and the RNA/DNA-world.

Amino Acids↗

Historical perspective: the problem of the origin of life in the context of developments in biology.

The structure of the history of scientific ideas on the origin of life, after Darwin's theory of evolution brought the problem into focus, is discussed. 19th-century theories in the mainstream of historical development already included some notion of chemical evolution. These theories were limited, however, by their reliance on a protoplasmic view of life, according to which the protoplasmic substance combines all vital properties. It was only when this holistic concept of protoplasm was abandoned that a clear distinction between different vital functions such as metabolism and replication was made. This led to two schools of thought in the origin of life field, one inspired by biochemistry and one by genetics. Oparin's theory, which was rooted in the metabolic traditions of biochemistry, provided a model which has had a lasting impact in methodological terms and which helped to transform the field from a largely theoretical one to an area of active research. Genetically based theories, on the other hand, had a delayed impact in this respect, because of long-lasting uncertainty regarding the structural basis of gene function.

Genes↗

Prebiotic cytosine synthesis: a critical analysis and implications for the origin of life.

A number of theories propose that RNA, or an RNA-like substance, played a role in the origin of life. Usually, such hypotheses presume that the Watson-Crick bases were readily available on prebiotic Earth, for spontaneous incorporation into a replicator. Cytosine, however, has not been reported in analyses of meteorites nor is it among the products of electric spark discharge experiments. The reported prebiotic syntheses of cytosine involve the reaction of cyanoacetylene (or its hydrolysis product, cyanoacetaldehyde), with cyanate, cyanogen, or urea. These substances undergo side reactions with common nucleophiles that appear to proceed more rapidly than cytosine formation. To favor cytosine formation, reactant concentrations are required that are implausible in a natural setting. Furthermore, cytosine is consumed by deamination (the half-life for deamination at 25 degrees C is approximately 340 yr) and other reactions. No reactions have been described thus far that would produce cytosine, even in a specialized local setting, at a rate sufficient to compensate for its decomposition. On the basis of this evidence, it appears quite unlikely that cytosine played a role in the origin of life. Theories that involve replicators that function without the Watson-Crick pairs, or no replicator at all, remain as viable alternatives.

Cytosine↗

[FeS/FeS2], a redox system for the origin of life (some experiments on the pyrite-hypothesis).

The FeS/FeS, redox system, whose importance is stressed in recent theories on the origin of life, has been tested experimentally. In this paper it is demonstrated by thermodynamical calculations as well as by experiments, that cyclohexanone, which served as model compound, can be reduced by the aforementioned redox system. Reactions were carried out in methanol and DMF at 25 degrees C and at 100 degrees C. Besides products that were synthesised in both solvents, like cyclohexanethiol and dicyclohexydisulphide, special compounds were obtained in methanol and in DMF, because of the involvement of the respective solvent in the reaction. Yields of reduced compounds were lower in methanol owing to compound that hindered the reduction (cyclohexylketal). With increasing temperature and duration the amount of reduced compounds increased. Further experiments have shown that 1,1-cyclohexanedithiol is likely to be a necessary intermediate for the reduced products. The experiments give evidence to the 'pyrite hypothesis', which postulates that the FeS/FeS2, redox system was of importance for the origin of life.

Cyclohexanones↗

A review of adsorption of amino acids on minerals: was it important for origin of life?

Minerals more readily adsorb amino acids with charged R groups than uncharged R groups, so that the incorporation of amino acids with charged R groups into peptides would be more frequent than for amino acids with uncharged R groups. However, 74% of the amino acids in the proteins of modern organisms contain uncharged R groups. Thus, what could have been the mechanisms that produced peptides/proteins with more amino acids with uncharged R groups than precursors with charged R groups? Should we expect the composition of amino acids adsorbed on minerals to be similar to those of present proteins? Was the adsorption of amino acids on minerals important for the origin of life? The lipid world offers an alternative view of origin of life. Liposomes contributed to elongation of peptides as well as select hydrophobic amino acids and peptides. These experiments could be showing the mechanism, which hydrophobic amino acids have been selected. However, liposomes have no influence on the stereoselectivity in the oligomerization of amino acids. In the present paper, several other mechanisms are also discussed that could produce peptides with a greater proportion of amino acids with uncharged R groups.

Adsorption↗