Quantum entanglement in photoactive prebiotic systems

This paper contains the review of quantum entanglement investigations in living systems, and in the quantum mechanically modelled photoactive prebiotic kernel systems. We define our modelled self-assembled supramolecular photoactive centres, composed of one or more sensitizer molecules, precursors of fatty acids and a number of water molecules, as a photoactive prebiotic kernel systems. We propose that life first emerged in the form of such minimal photoactive prebiotic kernel systems and later in the process of evolution these photoactive prebiotic kernel systems would have produced fatty acids and covered themselves with fatty acid envelopes to become the minimal cells of the Fatty Acid World. Specifically, we model self-assembling of photoactive prebiotic systems with observed quantum entanglement phenomena. We address the idea that quantum entanglement was important in the first stages of origins of life and evolution of the biospheres because simultaneously excite two prebiotic kernels in the system by appearance of two additional quantum entangled excited states, leading to faster growth and self-replication of minimal living cells. The quantum mechanically modelled possibility of synthesizing artificial self-reproducing quantum entangled prebiotic kernel systems and minimal cells also impacts the possibility of the most probable path of emergence of protocells on the Earth or elsewhere. We also examine the quantum entangled logic gates discovered in the modelled systems composed of two prebiotic kernels. Such logic gates may have application in the destruction of cancer cells or becoming building blocks of new forms of artificial cells including magnetically active ones.     

Polymer phosphorylases: clues to the emergence of non-replicative and replicative polymers

Polymer formation is arguably one of the essential factors that allowed the emergence, stabilisation and spread of life on Earth. Consequently, studies concerning biopolymers could shed light on the origins of life itself. Of particular interest are RNA and polysaccharide polymers, the archetypes of the contrasting proposed evolutionary scenarios and their respective polymerases. Nucleic acid polymerases were hypothesised, before their discovery, to have a functional similarity with glycogen phosphorylase. Further identification and characterisation of nucleic acid polymerases; particularly of polynucleotide phosphorylase (PNPase), provided experimental evidence for the initial premise. Once discovered, frequent similarities were found between PNPase and glycogen phosphorylase, in terms of catalytic features and biochemical properties. As a result, PNPase was seen as a model of primitive polymerase and used in laboratory precellular systems. Paradoxically, however, these similarities were not sufficient as an argument in favour of an ancestral common polymerisation mechanism prior to polysaccharides and polyribonucleotides. Here we present an overview of the common features shared by polymer phosphorylases, with new proposals for the emergence of polysaccharide and RNA polymers.     

What is Life? Defining Life in the Context of Emergent Complexity

Erwin Schrödinger defined life not only as a “self-reproducing” aperiodic crystal of DNA coding for proteins but within the context of living entities increasing their order by dissipating matter/energy gradients to maintain themselves away from equilibirium. Since then most definitions of life have focused on the former. But living cells do more than replicate their DNA. Cells also have membrane barriers across which metabolites must move, via which energy transduction as well as information processing occurs, and within which metabolic transformation occurs. An approach of complex systems dynamics, including nonequilibrium thermodynamics, may provide a more robust approach for defining life than a “naked replicator” at the origin of life. The crucial issue becomes the process of emergence of life from pre-biotic chemistry, concomitant with the emergence of function, information, and semiosis. Living entities can be viewed as bounded, informed autocatalytic cycles feeding off matter/energy gradients, exhibiting agency, capable of growth, reproduction, and evolution. Understanding how life might have emerged should sharpen our definition of what life is.     

Experimental evolution of complexity: in vitro emergence of intermolecular ribozyme interactions.

In the course of evolving variants of the Tetrahymena thermophila Group I ribozyme for improved DNA cleavage in vitro, we witnessed the unexpected emergence of a derived molecular species, capable of acting as a partner for the ribozyme, but no longer autocatalytic. This new RNA species exhibits a deletion in the catalytic core and participates in a productive intermolecular interaction with an active ribozyme, thus insuring its survival in the population. These novel RNA molecules have evolved a precise catalytic interaction with the Group I ribozyme and depend for their survival on the continued presence of active catalysts. This interaction hints at the complexity that may inevitably arise even in simple evolving systems.     

The emergence of life on Earth

Combined top-down and bottom-up research strategies and the principle of biological continuity were employed in an attempt to reconstruct a comprehensive origin of life theory, which is an extension of the coevolution theory (Lahav and Nir, Origins of Life Evol. Biosphere (1997) 27, 377-395). The resulting theory of emergence of templated-information and functionality (ETIF) addresses the emergence of living entities from inanimate matter, and that of the central mechanisms of their further evolution. It proposes the emergence of short organic catalysts (peptides and proto-ribozymes) and feedback-loop systems, plus their template-and-sequence-directed (TSD) reactions, encompassing catalyzed replication and translation of populations of molecules organized as chemical-informational feedback loop entities, in a fluctuating (wetting-drying) environment, functioning as simplified extant molecular-biological systems. The feedback loops with their TSD systems are chemically and functionally continuous with extant living organisms and their emergence in an inanimate environment may be defined as the beginning of life. The ETIF theory considers the emergence of bio-homochirality, a primordial genetic code, information and the incorporation of primordial metabolic cycles and compartmentation into the emerging living entities. This theory helps to establish a novel measure of biological information, which focuses on its physical effects rather than on the structure of the message, and makes it possible to estimate the time needed for the transition from the inanimate state to the closure of the first feedback-loop systems. Moreover, it forms the basis for novel laboratory experiments and computer modeling, encompassing catalytic activity of short peptides and proto-RNAs and the emergence of bio-homochirality and feedback-loop systems.     

Eutectic phase in water-ice: a self-assembled environment conducive to metal-catalyzed non-enzymatic RNA polymerization

Information and catalytic polymers play an essential role in contemporary cellular life, and their emergence must have been crucial during the complex processes that led to the assembly of the first living systems. Polymerization reactions producing these molecules would have had to occur in aqueous medium, which is known to disfavor such reactions. Thus, it was proposed early on that these polymerizations had to be supported by particular environments, such as mineral surfaces and eutectic phases in water-ice, which would have led to the concentration of the monomers out of the bulk aqueous medium and their condensation. This review presents the work conducted to understand how the eutectic phases in water-ice might have promoted RNA polymerization, thereby presumably contributing to the emergence of the ancient information and catalytic system envisioned by the 'RNA-World' hypothesis.     

Detecting autocatalytic, self-sustaining sets in chemical reaction systems

The ability of systems of molecular reactions to be simultaneously autocatalylic and sustained by some ambient 'food source' of simple molecules may have been an essential step in the origin of life. In this paper we first describe a polynomial-time algorithm that determines whether any given set of molecules, reactions and catalysations contains a subsystem that is both autocatalytic and able to be sustained from a given subset of the molecules. We also describe some combinatorial properties of this algorithm, and show how it can be used to find irreducible auto-catalysing and sustaining subsystems. In the second part of the paper we use the algorithm to investigate random catalytic networks-in particular, a model described by Kauffman. Using simulations and some analytic techniques we investigate the rate of catalysis that is required for the emergence of autocatalytic and sustaining subsystems.     

Evolution of a molecular switch: universal bacterial GTPases regulate ribosome function

The GTPases comprise a protein superfamily of highly conserved molecular switches adapted to many diverse functions. These proteins are found in all domains of life and often perform essential roles in fundamental cellular processes. Analysis of data from genome sequencing projects demonstrates that bacteria possess a core of 11 universally conserved GTPases (elongation factor G and Tu, initiation factor 2, LepA, Era, Obg, ThdF/TrmE, Ffh, FtsY, EngA and YchF). Investigations aimed at understanding the function of GTPases indicate that a second conserved feature of these proteins is that they elicit their function through interaction with RNA and/or ribosomes. An emerging concept suggests that the 11 universal GTPases are either necessary for ribosome function or transmitting information from the ribosome to downstream targets for the purpose of generating specific cellular responses. Furthermore, it is suggested that progenitor GTPases were early regulators of RNA function and may have existed in precursors of cellular systems driven by catalytic RNA. If this is the case, then a corollary of this hypothesis is that GTPases that do not bind RNA arose at a later time from an RNA-binding progenitor that lost the capability to bind RNA.     

Monte Carlo simulation of early molecular evolution in the RNA World

The origin of life remains a highly speculative field, mainly due to the shortage of our knowledge on prebiotic chemistry and basic understanding on the essence of life. In this context, computer simulation is expected to play an important role. For instance, the scenario concerning the genesis of the widely accepted RNA World remains blurry, though we have gathered some circumstantial evidence and fragmented knowledge on several supposed stages, including formation of polynucleotides from a prebiotic nucleotide pool, emergence of RNA replicases (RNA molecules catalyzing their own replication), and evolution of RNA replicases. It is highly valuable to simulate the stages as a continuous process to evaluate the plausibility of the supposition and study the rules involved. Here we construct a computer simulation on the process using Monte Carlo method. It demonstrates that primordial RNA replicases may appear and spread in a nucleotide pool provided they could recognize their own sequence and their complements as catalytic targets, and then may evolve to more efficient RNA replicases. Apart from its indication on the genesis of the RNA World, the vivid simulation of emergence of the “first replicative molecules” and their subsequent evolution is impressive and may help to get insight into “how could self-replication and Darwinian evolution, two key features of life, emerge in a non-life background?” thus improve our understanding of “what is life” when studying origins of life.     

Short-strong hydrogen bonds and a low barrier transition state for the proton transfer reaction in RNase A catalysis: a quantum chemical study

There is growing evidence that some enzymes catalyze reactions through the formation of short-strong hydrogen bonds as first suggested by Gerlt and Gassman. Support comes from several experimental and quantum chemical studies that include correlation energies on model systems. In the present study, the process of proton transfer between hydroxyl and imidazole groups, a model of the crucial step in the hydrolysis of RNA by the enzymes of the RNase A family, is investigated at the quantum mechanical level of density functional theory and perturbation theory at the MP2 level. The model focuses on the nature of the formation of a complex between the important residues of the protein and the hydroxyl group of the substrate. We have also investigated different configurations of the ground state that are important in the proton transfer reaction. The nature of bonding between the catalytic unit of the enzyme and the substrate in the model is investigated by Bader's atoms in molecule theory. The contributions of solvation and vibrational energies corresponding to the reactant, the transition state and the product configurations are also evaluated. Furthermore, the effect of protein environment is investigated by considering the catalytic unit surrounded by complete proteins--RNase A and Angiogenin. The results, in general, indicate the formation of a short-strong hydrogen bond and the formation of a low barrier transition state for the proton transfer model of the enzyme.     

Catalytic Activities Of [GADV]-Peptides

We have previously postulated a novel hypothesis for the origin of life, assuming that life on the earth originated from “[GADV]-protein world”, not from the “RNA world” (see Ikehara's review, 2002). The [GADV]-protein world is constituted from peptides and proteins with random sequences of four amino acids (glycine [G], alanine [A], aspartic acid [D] and valine [V]), which accumulated by pseudo-replication of the [GADV]-proteins. To obtain evidence for the hypothesis, we produced [GADV]-peptides by repeated heat-drying of the amino acids for 30 cycles ([GADV]-P₃₀) and examined whether the peptides have some catalytic activities or not. From the results, it was found that the [GADV]-P₃₀ can hydrolyze several kinds of chemical bonds in molecules, such as umbelliferyl-β-D-galactoside, glycine-p-nitroanilide and bovine serum albumin. This suggests that [GADV]-P₃₀ could play an important role in the accumulation of [GADV]-proteins through pseudo-replication, leading to the emergence of life. We further show that [GADV]-octapaptides with random sequences, but containing no cyclic compounds as diketepiperazines, have catalytic activity, hydrolyzing peptide bonds in a natural protein, bovine serum albumin. The catalytic activity of the octapeptides was much higher than the [GADV]-P₃₀ produced through repeated heat-drying treatments. These results also support the [GADV]-protein-world hypothesis of the origin of life (see Ikehara's review, 2002). Possible steps for the emergence of life on the primitive earth are presented.     

Discovery of novel inhibitors of LEDGF/p75-IN protein–protein interactions

Human lens epithelium-derived growth factor (LEDGF)/p75 plays an important role in the HIV life cycle by stimulating integrase (IN)-led viral DNA integration into cellular chromosomes. Mechanistic studies show the majority of IN inhibitors chelate magnesium ions in the catalytic active site, a region topologically distant from the LEDGF/p75 binding site. Compounds disrupting the formation of LEDGF/p75 and IN complexes serve as a novel mechanistic approach different from current antiretroviral therapies. We previously built pharmacophore models mimicking LEDGF/p75 residues and identified four classes of LEDGF/p75-IN inhibitors. Substructure and similarity searches yielded additional LEDGF/p75-IN inhibitors containing an acylhydrazone moiety. The most potent of the acylhydrazones inhibited LEDGF/p75-IN interaction with an IC₅₀ value of 400 nM. We explored structure–activity relationships (SAR) and identified new acylhydrazones, hydrazines, and diazenes as lead molecules for further optimization. Two lead LEDGF/p75-IN inhibitors showed antiviral activity.     

Catalytic RNA and the origin of genetic systems

The recent discovery of catalytic RNA molecules has provoked enormous interest in the origin of life and has given rise to new speculations about how living systems developed on the primitive earth. Here we outline why the discovery of catalytic RNA molecules has profound evolutionary implications, and then go on to discuss models for the emergence of metabolic complexity and protein synthesis in a primitive 'RNA world', emphasizing the constraints imposed on such models by genetical arguments.     

Microbial biosignatures in ancient deep-sea hydrothermal sulfides

Deep-sea hydrothermal systems provide ideal conditions for prebiotic reactions and ancient metabolic pathways and, therefore, might have played a pivotal role in the emergence of life. To understand this role better, it is paramount to examine fundamental interactions between hydrothermal processes, non-living matter, and microbial life in deep time. However, the distribution and diversity of microbial communities in ancient deep-sea hydrothermal systems are still poorly constrained, so evolutionary, and ecological relationships remain unclear. One important reason is an insufficient understanding of the formation of diagnostic microbial biosignatures in such settings and their preservation through geological time. This contribution centers around microbial biosignatures in Precambrian deep-sea hydrothermal sulfide deposits. Intending to provide a valuable resource for scientists from across the natural sciences whose research is concerned with the origins of life, we first introduce different types of biosignatures that can be preserved over geological timescales (rock fabrics and textures, microfossils, mineral precipitates, carbonaceous matter, trace metal, and isotope geochemical signatures). We then review selected reports of biosignatures from Precambrian deep-sea hydrothermal sulfide deposits and discuss their geobiological significance. Our survey highlights that Precambrian hydrothermal sulfide deposits potentially encode valuable information on environmental conditions, the presence and nature of microbial life, and the complex interactions between fluids, micro-organisms, and minerals. It further emphasizes that the geobiological interpretation of these records is challenging and requires the concerted application of analytical and experimental methods from various fields, including geology, mineralogy, geochemistry, and microbiology. Well-orchestrated multidisciplinary studies allow us to understand the formation and preservation of microbial biosignatures in deep-sea hydrothermal sulfide systems and thus help unravel the fundamental geobiology of ancient settings. This, in turn, is critical for reconstructing life's emergence and early evolution on Earth and the search for life elsewhere in the universe.     

Boron Enrichment in Martian Clay

We have detected a concentration of boron in martian clay far in excess of that in any previously reported extra-terrestrial object. This enrichment indicates that the chemistry necessary for the formation of ribose, a key component of RNA, could have existed on Mars since the formation of early clay deposits, contemporary to the emergence of life on Earth. Given the greater similarity of Earth and Mars early in their geological history, and the extensive disruption of Earth''s earliest mineralogy by plate tectonics, we suggest that the conditions for prebiotic ribose synthesis may be better understood by further Mars exploration.     

Towards a General Definition of Life

A new definition of life is proposed and discussed in the present article. It is formulated by modifying and extending NASA’s working definition of life, which postulates that life is a “self-sustaining chemical system capable of Darwinian evolution”. The new definition includes a thermodynamical aspect of life as a far from equilibrium system and considers the flow of information from the environment to the living system. In our derivation of the definition of life we have assumed the hypothesis, that during the emergence of life evolution had to first involve autocatalytic systems that only subsequently acquired the capacity of genetic heredity. The new proposed definition of life is independent of the mode of evolution, regardless of whether Lamarckian or Darwinian evolution operated at the origins of life and throughout evolutionary history. The new definition of life presented herein is formulated in a minimal manner and it is general enough that it does not distinguish between individual (metabolic) network and the collective (ecological) one. The newly proposed definition of life may be of interest for astrobiology, research into the origins of life or for efforts to produce synthetic or artificial life, and it furthermore may also have implications in the cognitive and computer sciences.

     

The origin of life: what we know,what we can know and what we will never know

The origin of life (OOL) problem remains one of the more challenging scientific questions of all time. In this essay, we propose that following recent experimental and theoretical advances in systems chemistry, the underlying principle governing the emergence of life on the Earth can in its broadest sense be specified, and may be stated as follows: all stable (persistent) replicating systems will tend to evolve over time towards systems of greater stability. The stability kind referred to, however, is dynamic kinetic stability, and quite distinct from the traditional thermodynamic stability which conventionally dominates physical and chemical thinking. Significantly, that stability kind is generally found to be enhanced by increasing complexification, since added features in the replicating system that improve replication efficiency will be reproduced, thereby offering an explanation for the emergence of life''s extraordinary complexity. On the basis of that simple principle, a fundamental reassessment of the underlying chemistry–biology relationship is possible, one with broad ramifications. In the context of the OOL question, this novel perspective can assist in clarifying central ahistoric aspects of abiogenesis, as opposed to the many historic aspects that have probably been forever lost in the mists of time.     

Clays in prebiological chemistry

Summary In this review an attempt is made to highlight the structures and properties of clay that may contribute to a better understanding of the role of clays in chemical evolution. The adsorption of organic molecules on clays has been demonstrated, as has the synthesis of bioorganic monomers in the presence of clays. For instance, amino acids (glycine, aspartic acid, threonine, alanine and others) as well as purines and pyrimidines, have been obtained from CO and NH₃ in the presence of clays at relatively high temperatures (250-325°C). Carbohydrates are also easily derived from formaldehyde at relatively low temperatures (80°C). The oligomerization of biochemical monomers, mediated by clays has also been shown to result in the formation of polymer molecules basic to life. For instance the condensation of amino acyl adenylates at room temperature in the presence of montmorillonite is known to yield polypeptides in discrete ranges of molecular weights with degrees of polymerization up to 56. Clays have also been found to affect the condensation of mononucleotides to oligonucleotides. Although the role of clays in the origin of metabolic pathways has not been demonstrated, it is possible that clays may have played a cooperative role with catalytic peptides in an intermediate stage of prebiological chemistry preceding the emergence of life on this planet.     

Enzymes in Low Water Systems

Water is fundamental for enzyme action and for formation of the three-dimensional structure of proteins. Hence, it may be assumed that studies on the interplay between water and enzymes can yield insight into enzyme function and formation. This has proven correct, because the numerous studies that have been made on the behavior of water-soluble and membrane enzymes in systems with a low water content (reverse micelles or enzymes suspended in nonpolar organic solvents) have revealed properties of enzymes that are not easily appreciated in aqueous solutions. In the low water systems, it has been possible to probe the relation between solvent and enzyme kinetics, as well as some of the factors that affect enzyme thermostability and catalysis. Furthermore, the studies show that low water environments can be used to stabilize conformers that exhibit unsuspected catalytic properties, as well as intermediates of enzyme function and formation that in aqueous media have relatively short life-times. The structure of enzymes in these unnatural conditions is actively being explored.     

The origin of the RNA world: co-evolution of genes and metabolism

Discoveries demonstrating that RNA can serve genetic, catalytic, structural, and regulatory roles have provided strong support for the existence of an RNA World that preceded the origin of life as we know it. Despite the appeal of this idea, it has been difficult to explain how macromolecular RNAs emerged from small molecules available on the early Earth. We propose here a mechanism by which mutual catalysis in a pre-biotic network initiated a progression of stages characterized by ever larger and more effective catalysts supporting a proto-metabolic network, and the emergence of RNA as the dominant macromolecule due to its ability to both catalyze chemical reactions and to be copied in a template-directed manner. This model suggests that many features of modern life, including the biosynthetic pathways leading to simple metabolites, the structures of organic and metal ion cofactors, homochirality, and template-directed replication of nucleic acids, arose long before the RNA World and were retained as pre-biotic systems became more sophisticated.