An Interpretive Review of the Origin of Life Research

Life appears to be a natural property of matter, but the problem of its origin only arose after early scientists refuted continuous spontaneous generation. There is no chance of life arising ‘all at once’, we need the standard scientific incremental explanation with large numbers of small steps, an approach used in both physical and evolutionary sciences. The necessity for considering both theoretical and experimental approaches is emphasized. After describing basic principles that are available (including the Darwin-Eigen cycle), the search for origins is considered under four main themes. These are the RNA-world hypothesis; potential intermediates between an RNA-world and a modern world via the evolution of protein synthesis and then of DNA; possible alternatives to an RNA-world; and finally the earliest stages from the simple prebiotic systems to RNA. The triplicase/proto-ribosome theory for the origin of the ribosome is discussed where triples of nucleotides are added to a replicating RNA, with the origin of a triplet code well-before protein synthesis begins. The length of the code is suggested to arise from the early development of a ratchet mechanism that overcomes the problem of continued processivity of an RNA-based RNA-polymerase. It is probable that there were precursor stages to RNA with simpler sugars, or just two nucleotides, but we do not yet know of any better alternatives to RNA that were likely to arise naturally. For prebiotic stages (before RNA) a flow-reactor model is suggested to solve metabolism, energy gradients, and compartmentation simultaneously – thus the intense interest in some form of flow reactor. If an autocatalytic cycle could arise in such a system we would be major steps ahead. The most likely physical conditions for the origin of life require further clarification and it is still unclear whether the origin of life is more of an entropy (information) problem (and therefore high temperatures would be detrimental), rather than a kinetic problem (where high temperatures may be advantageous).     

Error-reducing Structure of the Genetic Code Indicates Code Origin in Non-thermophile Organisms

During the RNA World, organisms experienced high rates of genetic errors, which implies that there was strong evolutionary pressure to reduce the errors’ phenotypical impact by suitably structuring the still-evolving genetic code. Therefore, the relative rates of the various types of genetic errors should have left characteristic imprints in the structure of the genetic code. Here, we show that, therefore, it is possible to some extent to reconstruct those error rates, as well as the nucleotide frequencies, for the time when the code was fixed. We find evidence indicating that the frequencies of G and C in the genome were not elevated. Since, for thermodynamic reasons, RNA in thermophiles tends to possess elevated G+C content, this result indicates that the fixation of the genetic code occurred in organisms which were either not thermophiles or that the code’s fixation occurred after the rise of DNA. Supplementary Materials Original data and programs are available at the author’s web site: .     

A possible circular RNA at the origin of life

The increasing volume of sequenced genomes and the recent techniques for performing in vitro molecular evolution have rekindled the interest for questions on the origin of life. Nevertheless, a gap continues to exist between the research on prebiotic chemistry and molecule generation, on one hand, and the study of molecular fossils preserved in genomes, on the other. Here we attempt to fill this gap by using some assumptions about the prebiotic scenario (including a strong stereochemical basis for the genetic code) to determine the RNA sequences more likely to appear and subsist. A set of minimal RNA rings is exhaustively determined; a subset of them is then selected through stability arguments, and a particular ring (AL ring) is finally singled out as the most likely winner of this prebiotic game. The rings happen to have several structural and statistical properties of modern genes: a repeated AUG codon appears spontaneously (and is thus made available for becoming a start signal), the form AUG/STOP emerges, and frequency patterns resemble those of present genes. The whole set of rings was also compared to a database of tRNAs, considering the conserved positions (located in the free parts of the molecule, essentially the loops); the ring that most closely matched tRNA sequences-and matched, in fact, the consensus of tRNA at all the aligned positions-was AL, the same ring independently selected before. The unselected emergence of gene-like features through two simple selection steps and the close similarity between the finally selected ring and tRNA (including some remarkable features of the resulting alignment) suggest a possible link between the prebiotic world and the first biological molecules, which is amenable for experimental testing. Even if our scenario is partially wrong, the unlikely coincidences should provide useful hints for other efforts.     

A Universal Definition of Life: Autonomy and Open-Ended Evolution

Life is a complex phenomenon that not only requires individual self-producing and self-sustaining systems but also a historical-collective organization of those individual systems, which brings about characteristic evolutionary dynamics. On these lines, we propose to define universally living beings as autonomous systems with open-ended evolution capacities, and we claim that all such systems must have a semi-permeable active boundary (membrane), an energy transduction apparatus (set of energy currencies) and, at least, two types of functionally interdependent macromolecular components (catalysts and records). The latter is required to articulate a 'phenotype-genotype' decoupling that leads to a scenario where the global network of autonomous systems allows for an open-ended increase in the complexity of the individual agents. Thus, the basic-individual organization of biological systems depends critically on being instructed by patterns (informational records) whose generation and reliable transmission cannot be explained but take into account the complete historical network of relationships among those systems. We conclude that a proper definition of life should consider both levels, individual and collective: living systems cannot be fully constituted without being part of the evolutionary process of a whole ecosystem. Finally, we also discuss a few practical implications of the definition for different programs of research.     

Analysis of Evolutionarily Independent Protein-RNA Complexes Yields a Criterion to Evaluate the Relevance of Prebiotic Scenarios

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Evolution of the capacity to evolve

Abstract During the past two decades, the fields of molecular biology and genetics have enabled study of far broader and more detailed aspects of evolutionary change than were possible when the evolutionary synthesis was elaborated in the mid‐twentieth century. The capacity for complete sequencing of both genes and proteins of all groups of organisms provide, simultaneously, the means to determine both the patterns and processes of evolution throughout the history of life. Increased knowledge of the genome documents the changing nature of its composition, mode of transmission, and the nature of the units of selection. Advances in evolutionary developmental biology demonstrate the conservation of genetic elements throughout multicellular organisms, and explain how control of the timing, position and nature of their expression has produced the extraordinary diversity of living plants and animals. The next generation of evolutionary biologists will benefit greatly from the increased integration of these new fields of research with those that are currently emphasized in the standard textbooks and journals.     

RNA Folding Argues Against a Hot-Start Origin of Life

Opinion is strongly divided on whether life arose on earth under hot or cold conditions, the hot-start and cold-start scenarios, respectively. The origin of life close to deep thermal vents appears as the majority opinion among biologists, but there is considerable biochemical evidence that high temperatures are incompatible with an RNA world. To be functional, RNA has to fold into a three-dimensional structure. We report both theoretical and experimental results on RNA folding and show that (as expected) hot conditions strongly reduce RNA folding. The theoretical results come from energy-minimization calculations of the average extent of folding of RNA, mainly from 0–90°C, for both random sequences and tRNA sequences. The experimental results are from circular-dichroism measurements of tRNA over a similar range of temperatures. The quantitative agreement between calculations and experiment is remarkable, even to the shape of the curves indicating the cooperative nature of RNA folding and unfolding. These results provide additional evidence for a lower temperature stage being necessary in the origin of life. Received: 1 March 2000 / Accepted: 14 June 2000     

Montmorillonite,Oligonucleotides, RNA and Origin of Life

Na-montmorillonite prepared from Volclay by the titration method facilitates the self-condensation of ImpA, the 5'-phosphorimidazolide derivative of adenosine. As was shown by AE-HPLC analysis and selective enzymatic hydrolysis of products, oligo(A)s formed in this reaction are 10 monomer units long and contain 67% 3',5'-phosphodiester bonds (Ferris and Ertem, 1992a). Under the same reaction conditions, 5'-phosphorimidazolide derivatives of cytidine, uridine and guanosine also undergo self-condensation producing oligomers containing up to 12-14 monomer units for oligo(C)s to 6 monomer units for oligo(G)s. In oligo(C)s and oligo(U)s, 75-80% of the monomers are linked by 2',5'-phosphodiester bonds. Hexamer and higher oligomers isolated from synthetic oligo(C)s formed by montmorillonite catalysis, which contain both 3',5'- and 2',5'-linkages, serve as catalysts for the non-enzymatic template directed synthesis of oligo(G)s from activated monomer 2-MeImpG, guanosine 5'-phospho-2-methylimidazolide (Ertem and Ferris, 1996). Pentamer and higher oligomers containing exclusively 2',5'-linkages, which were isolated from the synthetic oligo(C)s, also serve as templates and produce oligo(G)s with both 2',5'- and 3',5'-phosphodiester bonds. Kinetic studies on montmorillonite catalyzed elongation rates of oligomers using the computer program SIMFIT demonstrated that the rate constants for the formation of oligo(A)s increased in the order of 2-mer < 3-mer < 4-mer ... < 7-mer (Kawamura and Ferris, 1994). A decameric primer, dA(pdA)8pA bound to montmorillonite was elongated to contain up to 50 monomer units by daily addition of activated monomer ImpA to the reaction mixture (Ferris, Hill and Orgel, 1996). Analysis of dimer fractions formed in the montmorillonite catalyzed reaction of binary and quaternary mixtures of ImpA, ImpC, 2-MeImpG and ImpU suggested that only a limited number of oligomers could have formed on the primitive Earth rather than equal amounts of all possible isomers (Ertem and Ferris, 2000). Formation of phosphodiester bonds between mononucleotides by montmorillonite catalysis is a fascinating discovery, and a significant step forward in efforts to find out how the first RNA-like oligomers might have formed in the course of chemical evolution. However, as has been pointed out in several publications, these systems should be regarded as models rather than a literal representation of prebiotic chemistry (Orgel, 1998; Joyce and Orgel, 1999; Schwartz, 1999).     

RNA Ligation and the Origin of tRNA

A straightforward origin of transfer RNA,(tRNA), is difficult to envision because of the apparentlycomplex idiosyncratic interaction between the D-loop and T-loop. Recently, multiple examples of the T-loop structuralmotif have been identified in ribosomal RNA. These examplesshow that the long-range interactions between the T-loop andD-loops seen in tRNA are not an essential part of the motifbut rather are facilitated by it. Thus, the core T-loopstructure could already have existed in a small RNA prior tothe emergence of the tRNA. The tRNA might then have arisenby expansion of an RNA that carried the motif. With thisidea in mind, Di Giulio's earlier hypothesis that tRNAevolved by a simple duplication or ligation of a minihelixRNA was re-examined. It is shown that an essentially moderntRNA structure can in fact be generated by the ligation oftwo 38-nucleotide RNA minihelices of appropriate sequence.Although rare, such sequences occur with sufficientfrequency, (1 in 3 × 10⁷), that they could be found in astandard in vitro RNA selection experiment. Theresults demonstrate that a series of RNA duplications, aspreviously proposed, can in principal account for the originof tRNA. More generally, the results point out that RNAligation can be a powerful driving force for increasedcomplexity in the RNA World.     

A new theoretical model for the origin of amino acid homochirality

Amino acid homochirality, as a unique behavior of life, could have originated synchronously with the genetic code. In this paper, phosphoryl amino-acid-5′-nucleosides with P-N bond are postulated to be a chiral origin model in prebiotic molecular evolution. The enthalpy change in the intramolecular interaction between the nucleotide base and the amino-acid side-chain determines the stability of the particular complex, resulting in a preferred conformation associated with the chirality of amino acids. Based on the theoretical model, our experiments and calculations show that the chiral selection of the earliest amino acids for L-enantiomers seems to be a strict stereochemical/physicochemical determinism. As other amino acids developed biosynthetically from the earliest amino acids, we infer that the chirality of the later amino acids was inherited from the precursor amino acids. This idea probably goes far back in history, but it is hoped that it will be a guide for further experiments in this area.     

Thermal Energy and the Origin of Life

Life has evolved on Earth with electromagnetic radiation (light), fermentable organic molecules, and oxidizable chemicals as sources of energy. Biological use of thermal energy has not been observed although heat, and the thermal gradients required to convert it into free energy, are ubiquitous and were even more abundant at the time of the origin of life on Earth. Nevertheless, Earth-organisms sense thermal energy, and in suitable environments may have gained the capability to use it as energy source. It has been proposed that the first organisms obtained their energy by a first protein named pF₁ that worked on a thermal variation of the binding change mechanism of today's ATP sythase enzyme. Organisms using thermosynthesis may still live where light or chemical energy sources are not available. Possible suitable examples are subsurface environments on Earth and in the outer Solar System, in particular the subsurface oceans of the icy satellites of Jupiter and Saturn.     

A Research Proposal on the Origin Of Life. Closing Lecture given at the ISSOL Congress in Oaxaca,Mexico, on July 4, 2002

This paper describes some experiments the author would haveliked to carry out if he had started earlier in the origin-of-life field.The proposal is preceded by a hypothetical outline of the mainevents in the origin of life. According to this outline, the emergence oflife amounts to the transition between two kinds of chemistry: 1) cosmic chemistry, which is beginning to be understood and mostlikely provided the building blocks with which life was first constructed; and 2)biochemistry, the well-known set of enzyme-catalyzedmetabolic reactions that support all living organisms today and must havesupported the universal common ancestor, or LUCA, from which all known formsof life are derived. The pathway leading from one to the other of thosetwo chemistries may be divided into three stages, defined as the pre-RNA, RNA, and protein-DNA stages. A briefsummary of the events that may have occurred in these three stages and ofthe possible underlying mechanisms is given. It is emphasized that theseevents were chemical in nature and, especially, that theymust have prefigured present-day biochemical processes. Protometabolismand metabolism, it is argued, must have been congruent. With congruence as the underlying working hypothesis, threeproblems open to experimental investigation are considered: 1) the involvementof 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 RNAmolecules.     

The Cold Origin of Life: A. Implications Based On The Hydrolytic Stabilities Of Hydrogen Cyanide And Formamide

It has been suggested that hydrogen cyanide(HCN) would not have been present in sufficient concentrationto polymerize in the primitive ocean to produce nucleic acidbases and amino acids. We have measured the hydrolysis ratesof HCN and formamide over the range of 30–150 °C and pH 0–14,and estimated the steady state concentrations in theprimitive ocean. At 100 °C and pH 8, the steady stateconcentration of HCN and formamide were calculated to be7 × 10^-13 M and 1 × 10^-15 M, respectively. Thus, itseems unlikely that HCN could have polymerized in a warmprimitive ocean. It is suggested that eutectic freezing mighthave been required to have concentrated HCN sufficiantly forit to polymerize. If the HCN polymerization was important forthe origin of life, some regions of the primitive earth mighthave been frozen.     

Serpentinite and the dawn of life

Submarine hydrothermal vents above serpentinite produce chemical potential gradients of aqueous and ionic hydrogen, thus providing a very attractive venue for the origin of life. This environment was most favourable before Earth's massive CO(2) atmosphere was subducted into the mantle, which occurred tens to approximately 100 Myr after the moon-forming impact; thermophile to clement conditions persisted for several million years while atmospheric pCO(2) dropped from approximately 25 bar to below 1 bar. The ocean was weakly acid (pH ～ 6), and a large pH gradient existed for nascent life with pH 9-11 fluids venting from serpentinite on the seafloor. Total CO(2) in water was significant so the vent environment was not carbon limited. Biologically important phosphate and Fe(II) were somewhat soluble during this period, which occurred well before the earliest record of preserved surface rocks approximately 3.8 billion years ago (Ga) when photosynthetic life teemed on the Earth and the oceanic pH was the modern value of approximately 8. Serpentinite existed by 3.9 Ga, but older rocks that might retain evidence of its presence have not been found. Earth's sequesters extensive evidence of Archaean and younger subducted biological material, but has yet to be exploited for the Hadean record.     

Origin of symbol-using systems: speech,but not sign,without the semantic urge

Natural language—spoken and signed—is a multichannel phenomenon, involving facial and body expression, and voice and visual intonation that is often used in the service of a social urge to communicate meaning. Given that iconicity seems easier and less abstract than making arbitrary connections between sound and meaning, iconicity and gesture have often been invoked in the origin of language alongside the urge to convey meaning. To get a fresh perspective, we critically distinguish the origin of a system capable of evolution from the subsequent evolution that system becomes capable of. Human language arose on a substrate of a system already capable of Darwinian evolution; the genetically supported uniquely human ability to learn a language reflects a key contact point between Darwinian evolution and language. Though implemented in brains generated by DNA symbols coding for protein meaning, the second higher-level symbol-using system of language now operates in a world mostly decoupled from Darwinian evolutionary constraints. Examination of Darwinian evolution of vocal learning in other animals suggests that the initial fixation of a key prerequisite to language into the human genome may actually have required initially side-stepping not only iconicity, but the urge to mean itself. If sign languages came later, they would not have faced this constraint.     

Science and the Concept of Evolution: From the Big Bang to the Origin and Evolution of Life

The common thread of evolution runs through all science disciplines, and the concept of evolution enables students to better understand the nature of the universe and our origins. “Science and the Concept of Evolution” is one of two interdisciplinary science Core courses taken by Dowling College undergraduates as part of their General Education requirements. The course examines basic principles and methods of science by following the concept of evolution from the big bang to the origin and evolution of life. Case studies of leading scientists illustrate how their ideas developed and contributed to the evolution of our understanding of the world. Evidences for physical, chemical, and biological evolution are explored, and students learn to view the evolution of matter and of ideas as a natural process of change over space and time.     

Enantiomeric Crystallization from DL-Aspartic and DL-Glutamic Acids: Implications for Biomolecular Chirality in the Origin of Life

Amino acids in living systems consist almost exclusively of the L-enantiomer. How and when this homochiral characteristic of life came to be has been a matter of intense investigation for many years. Among the hypotheses proposed to explain theappearance of chiral homogeneity, the spontaneous resolution of conglomerates seems one of the most plausible. Racemic solids may crystallize from solution either as racemic compounds(both enantiomeric molecules in the same crystal), or lesscommonly as conglomerates (each enantiomer molecule separate indifferent enantiomeric crystals). Only conglomerates can developa spontaneous resolution (one of the enantiomeric molecule crystallizes preferentially, the other one remains in solution).Most of natural amino acids are racemic compounds at moderatetemperatures. How can we expect a hypothetical spontaneous resolution of these amino acids if they are not conglomerates?In this paper we show how DL-aspartic and DL-glutamic amino acids(racemic compounds), crystallize at ambient conditions as trueconglomerates. The experimental conditions here described,that allows this `anomalous' behaviour, could be also found innatural sedimentary environments. We suggest that these experimental procedures and its natural equivalents, have apotential interest for the investigation of the spontaneous resolution of racemic compounds comprising molecules associatedwith the origin of life.     

Origin of amino acid homochirality: relationship with the RNA world and origin of tRNA aminoacylation

The origin of homochirality of l-amino acids has long been a mystery. Aminoacylation of tRNA might have provided chiral selectivity, since it is the first process encountered by amino acids and RNA. An RNA minihelix (progenitor of the modern tRNA) was aminoacylated by an aminoacyl phosphate oligonucleotide that exhibited a clear preference for l- as opposed to d-amino acids. A mirror-image RNA system with l-ribose exhibited the opposite selectivity, i.e., it exhibited an apparent preference for the d-amino acid. The selectivity for l-amino acids is based on the stereochemistry of RNA. The side chain of d-amino acids is located much closer to the terminal adenosine of the minihelix, causing them collide and interfere during the amino acid-transfer step. These results suggest that the putative RNA world that preceded the protein theatre determined the homochirality of l-amino acids through tRNA aminoacylation.     

The Cold Origin of Life: B. Implications Based on Pyrimidines and Purines Produced From Frozen Ammonium Cyanide Solutions

A wide variety of pyrimidines and purineswere identified as products of a dilute frozen ammoniumcyanide solution that had been held at –78°C for 27 years.This demonstrates that both pyrimidines and purines couldhave been produced on the primitive earth in a short time byeutectic concentration of HCN, even though the concentrationof HCN in the primitive ocean may have been low. We suggestthat eutectic freezing is the most plausible demonstratedmechanism by which HCN polymerizations could have producedbiologically important prebiotic compounds.     

Genetic material in the early evolution of bacteria

DNA and RNA are nucleic acids that cells and viruses use to produce copies of themselves. However, there is an immense paucity of knowledge on how these nucleic acids originated and changed as early bacteria became capable of growth and cell division. One possibility is that parallel evolution of the genetic code and protein synthesis was required for assembly of the first cells capable of growth and division. It is also possible that DNA-RNA duplices were intermediate genetic material in the early assembly of the first cells. These ideas will be discussed as well as other aspects of the assembly of the first cells on the Earth.