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Random biochemical networks: the probability of self-sustaining autocatalysis.

We determine conditions under which a random biochemical system is likely to contain a subsystem that is both autocatalytic and able to survive on some ambient 'food' source. Such systems have previously been investigated for their relevance to origin-of-life models. In this paper we extend earlier work, by finding precisely the order of catalysation required for the emergence of such self-sustaining autocatalytic networks. This answers questions raised in earlier papers, yet also allows for a more general class of models. We also show that a recently described polynomial-time algorithm for determining whether a catalytic reaction system contains an autocatalytic, self-sustaining subsystem is unlikely to adapt to allow inhibitory catalysation--in this case we show that the associated decision problem is NP-complete.

Biochemical Phenomena↗

Expression of acetylcholine (ACh) and ACh-synthesizing activity in Archaea.

Acetylcholine (ACh) is known generally as the neurotransmitter in the mammalian central and peripheral cholinergic nervous systems. However, ACh is also widely expressed in non-neuronal animal tissues and in plants, fungi and bacteria, where it is likely involved in the transport of water, electrolytes and nutrients, and in modulating various other cell functions. We have investigated the expression of ACh and ACh-synthesizing activity in various strains of Archaea, which are situated between Bacteria and Eucarya in the universal phylogenetic tree. Using a sensitive and specific radioimmunoassay, differing levels of ACh were detected in the Hyperthermophiles Thermococcus kodakaraensis KOD1, Sulfolobus tokodaii strain 7 and Pyrobaculum calidifontis VA1; the Methanogens Methanothermobacter thermautotrophicus deltaH and Methanosarcina barkeri; and the Halophiles Halobacterium sp. NRC-1 and Haloferax volcanii. T. kodakaraensis KOD1 expressed the highest levels of ACh among the Archaea tested; moreover, the substance expressed was verified to be ACh using high-performance liquid chromatography with electrochemical detection. Varying degrees of ACh-synthesizing activity were also identified in all of the strains, and the activity of bromoACh-sensitive choline acetyltransferase, an enzyme responsible for ACh synthesis in the nervous system, was detected in T. kodakaraensis KOD1. Our findings demonstrate that ACh and ACh-synthesizing activity are both expressed in evolutionally old Archaea. In the context of the recent discovery of non-neuronal ACh in bacteria, fungi, plants and animals, these findings support the notion that ACh has been expressed in organisms from the origin of life on the earth, functioning as a local mediator as well as a neurotransmitter.

Acetylcholine↗

Developmental and metabolic implications of the hypoxic ventilatory response.

This review explores the evidence to support the leading hypothesis that the metabolic response to hypoxia early in life provides the pathophysiological basis for the metabolic syndrome. Hypoxia is a frequent occurrence during early development and induces a state of energy depletion that triggers a wide range of 'metabolic' responses to preserve homeostasis. Recent interest in the sequelae of energy depletion through hypoxic mechanisms has grown, particularly because of demonstrated links with ensuing metabolic abnormalities and increased risk for future cardiovascular disease. The 'metabolic syndrome' refers to the combination of obesity, hyperinsulinaemia, dyslipidaemia and hypertension in adults. The metabolic responses to energy depletion during early development provide explanations for some of the mechanisms that ultimately lead to serological features of metabolic dysfunction in children with sleep-disordered breathing. Thus, the acute compensatory response of energy conservation to hypoxia during early development at the cellular, serological and whole organism levels suggests that the metabolic abnormalities that develop later in life may in fact originate very early in life; in other words, constitute early life antecedents of adult disease. Evidence regarding the circumstances under which responses to hypoxia become maladaptive will be discussed, with a focus on chronic conditions and those associated with intermittent respiratory dysfunction such as sleep-disordered breathing.

Humans↗

Enzymatic reactions in liposomes using the detergent-induced liposome loading method.

Microcompartmentalization is a crucial step in the origin of life. More than 30 years ago, Oparin et al. proposed models based on biochemical reactions taking place in so-called coacervates. Their intention was to develop systems with which semipermeable microcompartments could be established. In the present work we follow their intuition, but we use well-characterized bilayer structures instead of the poorly characterized coacervates. Liposomes from phospholipids can be used as microreactors but they exhibit only a modest permeability and, therefore, chemical reactions occurring inside these structures are depleted after a relatively short period. Here it is shown that even highly stable liposomes from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) can be used as semipermeable microreactors when treated with sodium cholate. Using this kind of mixed liposomes, we describe a biochemical reaction occurring inside the liposomes while the same reaction is prevented in the external medium. In addition, we show that this cholate-induced permeability of POPC bilayers can even be used to load macromolecules such as enzymes from the outside.

Cholates↗

Gas chromatography for in situ analysis of a cometary nucleus III. Multi-capillary column system for the cometary sampling and composition experiment of the Rosetta lander probe.

The cometary sampling and composition (COSAC) experiment is one of the principal experiments of the surface lander probe of the European Space Agency Rosetta mission to be launched in January 2003. The instrument is designed for the in situ chemical analysis of a cometary nucleus as the details of the nucleus composition are of primary importance for understanding both the formation of the solar system, and the origin of life on Earth. The COSAC experiment consists of an evaporation/pyrolysis device and two analytical systems: a multi-column gas chromatograph and a high-resolution time-of-flight mass spectrometer which may either be operated alone or in a coupled mode. The gas chromatograph includes five general purpose chromatographic columns and three chiral ones, all mounted in parallel. Taking into account the chemical species potentially present in the cometary nucleus as well as the space constraints, a set of five complementary columns was selected to perform the separation and identification of the compounds present in the cometary nucleus. This set of columns includes a carbon molecular sieve porous-layer open tubular (PLOT) column used for the separation of both the noble and other permanent gases, and the C1-C2 hydrocarbons. A second PLOT column uses a divinylbenzene-ethylene glycol-dimethylacrylate porous polymer as stationary phase for the analysis of a wide range of C1-C2 organic molecules, Two complementary wall-coated open tubular (WCOT) columns with polydimethylsiloxane (PDMS) liquid stationary phases, one containing cyanopropyl-phenylsiloxane and the other diphenylsiloxane groups, are designed to target the same range of organic compounds (C3-C7) which could be representative of the widest range of cometary compounds. A third WCOT column with an apolar stationary phase made of non-substituted PDMS is used for the separation and identification of higher-molecular-mass compounds (up to C10) and aromatic species (monoaromatic and polyaromatic). This paper describes these five general-purpose capillary PLOT and WCOT columns, selected to be used in the COSAC GC system. The analytical capabilities are examined with a special emphasis on the exobiological and planetological implications.

Chromatography, Gas↗

Comma-free and synchronizable codes.

Shepherd (1981. Proc. natn. Acad. Sci. U.S.A. 78, 1596-1600), Clarke (1982. J. theor. Biol. 99, 397-403), Crick et al. (1976. Origins of Life 7, 389) have put forward the possibility that there was a code, ancestral to the existing genetic code, which was non-degenerate and comma-free. The point of a comma-free code, as first proposed in Crick et al. (1957), is that it provides immunity from frameshift reading errors. In this paper it is argued that if frameshift error immunity is to be used as a selection factor in guiding the search for a hypothetical ancestral code, then the appropriate mathematical formulation of this characteristic is not comma-freeness but synchronizability. The calling card of the comma-free notion is that it results in a limit of 20 on the number of sense codons when applied to the genetic coding system. But so does synchronizability, which includes comma-freeness as a special case. Further, using synchronizability as a constraint instead of comma-freeness yields roughly 3000 times as many potential models for an ancestral code. In particular, the RNY model becomes more compatible with immunity from frameshift error as an evolutionary constraint.

Base Sequence↗

Coevolution of viruses with hosts and vectors and possible paleontology.

The coevolution of viruses with their hosts and vectors depends on the evolution of the hosts and vectors coupled with factors involved in virus evolution. The long-term perspective involves the origin of life forms, the evolution of host and vector (especially arthropods) kingdoms and families, and changes in biological diversity induced mainly by the last five great extinctions. In the medium term, the diversification of hosts and vectors is important, and in the short term, recent events, especially humans, have had a great impact on virus coevolution. As there are few, if any, examples of conventional fossils of viruses, evidence for their evolution related to host and vector evolution is being found from other sources, especially virus-induced cellular structures and recent developments in molecular biology. Recognizing these other sources is becoming important for paleontologists gaining an understanding of the influence that viruses have had on the development of higher organisms.

Animals↗

Why implementing the space option is necessary for society.

For several years, specialized agencies have been searching for "new programs" that could reinvigorate the support for space activities and stop their budgets' decline of. But the same time, they have been retrenching by focusing on collecting and distributing information, putting scientific research as their core projects. On a planet soon to host a 10-billion population that will impact the biosphere's workings as never before, at a time when many governments and organizations see the virtue in the management of scarcity, musing on the origins of life and of the solar system can hardly be expected to be invested with high priority. The space option arose from the analysis of the issues confronting humanity. In reviewing the material needs of the human population in the near future, the analysis finds that the impact on the biosphere will perforce be much larger than it usually seems to be acceptable to assume.

Conservation of Natural Resources↗

Randomness and biospecificity: random copolymers are capable of biospecific molecular recognition in living systems.

Biospecific molecular recognition in living systems is known to be based on the lock and key principle as proposed by Emil Fischer. Based on this concept, biospecific polymers have been produced synthetically by attaching biospecific 'keys' to the polymer chain. We postulate that biospecificity can be achieved by alternative means, namely random substitution of a preformed polymer with suitable chemical groups or random copolymerization of suitable functional monomers. Such polymers, we suggest, will contain arrangements of the chemical functions which mimic natural biospecific sites and the probability of occurrence of such arrangements will depend on the average composition of the polymer. In support of this principle, we have developed several functional random copolymer systems which possess a variety of biological properties depending on the type of chemical function. Examples are: polymers possessing anticoagulant properties similar to those of heparin; polymers which interact specifically with components of the immune system; and polymers which, in contact with cells, affect their growth and metabolism. In the case of statistical copolymers possessing 'DNA-like' properties obtained by phosphorylation of hydroxylated polystyrene derivatives, Monte Carlo simulations were used to determine the distribution of phosphodiester (PDE) groups along the chains and to compute the probabilities of occurrence of particular arrangements of PDE found in the 'DNA-like' sites. The results showed that these sites are made up of PDE groups separated by distances that closely match those between the same groups along a generatrix of the DNA double-helix cylinder. These findings offer the prospect of manufacturing polymeric biomaterials endowed with biomimetic character. Moreover, they provide the basis for a hypothesis regarding the appearance of biospecificity at the origin of life, suggesting that biospecific structures may have evolved by natural selection from purely random copolymers. It is likely therefore that biospecificity is a continuous function of randomness, arising from purely statistical distributions of reactivity and evolving into precisely defined structures such as those involved in ligand-receptor interactions.

Animals↗

Organics produced by ion irradiation of ices: some recent results.

Some results, recently obtained from laboratory experiments of ion irradiation of ice mixtures containing H, C, N, and O, are here summarized. They are relevant to the formation and evolution of complex organics on interstellar dust, comets and other small bodies in the external Solar System. In particular the formation of CN-bearing species is discussed. Interstellar dust incorporated into primitive Solar System bodies and subsequently delivered to the early Earth, may have contributed to the origin of life. The delivery of CN-bearing species seems to have been necessary because molecules containing the cyanogen bond are difficult to be produced in an environment that is not strongly reducing as that of the early Earth probably was. Moreover we report on an ongoing research program concerning the interaction between refractory materials produced by ion irradiation of simple ices and biological materials (amino acids, proteins, cells).

Argon↗

Quantum chemical calculations of infrared spectra for the identification of unknown compounds by GC/FTIR/MS in exobiological simulation experiments.

Gas chromatography/Fourier transform IR spectroscopy/mass spectrometry (GC/FTIR/MS) is a powerful tool for the separation and unambiguous identification of complex mixtures of organic compounds, where the use of two kinds of spectra allows to significantly increase identification reliability. The simplest situation is when acquired spectra can be found in IR and MS databases, or appropriate standards are available; but this is not always the case. Some simulation experiments related to the origins of life and exobiology (e.g., simulation of amino acid pyrolysis during atmospheric entry of space bodies) can be a typical example when one encounters with numerous unknown compounds. To assist their identification by GC/FTIR/MS, recently we suggested quantum chemical calculations of infrared spectra in order to compare them to IR spectra acquired experimentally. The present work summarizes the results obtained by semi-empirical and ab initio methods, discusses their advantages and limitations, considering as test compounds some cyclic amides and amidines derived from amino acids, saturated and unsaturated nitriles (including those of interest for the Titan atmospheric chemistry), acetylenes and some other nitrogen compounds.

Amino Acids↗

From the interstellar clouds, through the inner to the outer solar system: a universally distributed complex organic chemistry. Preface.

High molecular weight organic compounds are involved in the chemistry and physics of many astrophysical and planetary objects. They are or should be present in interstellar dust, in comets and meteorites, in the Giant planets and Titan, in asteroids Triton and icy satellites. They represent a class of very complex organic material, part of which may have played a role in the origin of life on Earth. Thus they directly concern prebiotic chemistry and exobiology.

Cosmic Dust↗

Complex organics in laboratory simulations of interstellar/cometary ices.

We present the photochemical and thermal evolution of both non-polar and polar ices representative of interstellar and pre-cometary grains. Ultraviolet photolysis of the non-polar ices comprised of O2, N2, and CO produces CO2, N2O, O3, CO3, HCO, H2CO, and possibly NO and NO2. When polar ice analogs (comprised of H2O, CH3OH, CO, and NH3) are exposed to UV radiation, simple molecules are formed including: H2, H2CO, CO2, CO, CH4, and HCO (the formyl radical). Warming produces moderately complex species such as CH3CH2OH (ethanol), HC(=O)NH2 (formamide), CH3C(=O)NH2 (acetamide), R-CN and/or R-NC (nitriles and/or isonitriles). Several of these are already known to be in the interstellar medium, and their presence indicates the importance of grain processing. Infrared spectroscopy, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, and gas chromatography-mass spectrometry demonstrate that after warming to room temperature what remains is an organic residue composed primarily of hexamethylenetetramine (HMT, C6H12N4) and other complex organics including the amides above and polyoxymethylene (POM) and its derivatives. The formation of these organic species from simple starting mixtures under conditions germane to astrochemistry may have important implications for the organic chemistry of interstellar ice grains, comets and the origins of life.

Astronomical Phenomena↗

Exobiological exploration of Mars.

Of all the other planets in the solar system, Mars remains the most promising for further elucidating concepts about chemical evolution and the origin of life. Strategies were developed to pursue three exobiological objectives for Mars exploration: determining the abundance and distribution of the biogenic elements and organic compounds, detecting evidence of an ancient biota on Mars, and determining whether indigenous organisms exist anywhere on the planet. The three strategies are quite similar and, in fact, share the same sequence of phases. In the first phase, each requires global reconnaissance and remote sensing by orbiters to select sites of interest for detailed in situ analyses. In the second phase, lander missions are conducted to characterize the chemical and physical properties of the selected sites. The third phase involves conducting "critical" experiments at sites whose properties make them particularly attractive for exobiology. These critical experiments would include, for example, identification of organics, detection of fossils, and detection of extant life. The fourth phase is the detailed analysis of samples returned from these sites in Earth-based laboratories to confirm and extend previous discoveries. Finally, in the fifth phase, human exploration is needed to establish the geological settings for the earlier findings or to discover and explore sites that are not accessible to robotic spacecraft.

Evolution, Chemical↗

Free energy and information contents of conformons in proteins and DNA.

Sequence-specific conformational strains (SSCS) of biopolymers that carry free energy and genetic information have been called conformons, a term coined independently by two groups over two and a half decades ago [Green, D.E., Ji, S., 1972. The electromechanochemical model of mitochondrial structure and function. In: Schultz, J., Cameron, B.F. (Eds.), Molecular Basis of Electron Transport. Academic Press, New York, pp. 1-44; Volkenstein, M.V., 1972. The Conformon. J. Theor. Biol. 34, 193-195]. Conformons provide the molecular mechanisms necessary and sufficient to account for all biological processes in the living cell on the molecular level in principle--including the origin of life, enzymic catalysis, control of gene expression, oxidative phosphorylation, active transport, and muscle contraction. A clear example of SSCS is provided by SIDD (strain-induced duplex destabilization) in DNA recently reported by Benham [Benham, C.J., 1996a. Duplex destabilization in superhelical DNA is predicted to occur at specific transcriptional regulatory regions. J. Mol. Biol. 255, 425-434; Benham, C.J., 1996b. Computation of DNA structural variability--a new predictor of DNA regulatory regions. CABIOS 12(5), 375-381]. Experimental as well as theoretical evidence indicates that conformons in proteins carry 8-16 kcal/mol of free energy and 40-200 bits of information, while those in DNA contain 500-2500 kcal/mol of free energy and 200-600 bits of information. The similarities and differences between conformons and solitons have been analyzed on the basis of the generalized Franck-Condon principle [Ji, S., 1974a. A general theory of ATP synthesis and utilization. Ann. N.Y. Acad. Sci. 227, 211-226; Ji, S., 1974b. Energy and negentropy in enzymic catalysis. Ann. N.Y. Acad. Sci. 227, 419-437]. To illustrate a practical application, the conformon theory was applied to the molecular-clamp model of DNA gyrase proposed by Berger and Wang [Berger, J.M., Wang, J.C., 1996. Recent developments in DNA topoisomerases II structure and mechanism. Curr. Opin. Struct. Biol. 6(1), 84-90], leading to the proposal of an eight-step molecular mechanism for the action of the enzyme. Finally, a set of experimentally testable predictions has been formulated on the basis of the conformon theory.

Animals↗

The late stage of genetic code structuring took place at a high temperature.

The correlation between the optimal growth temperature of organisms and a thermophily index based on the propensity of amino acids to enter more frequently into (hyper)thermophile proteins is used to conduct an analysis aiming to establish whether genetic code structuring took place at a low or a high temperature. If the number of codons attributed to the various amino acids in the genetic code constitutes an estimate of the mean amino acid composition of proteins produced when the genetic code was definitively structured, then the thermophily index can also be associated to the genetic code. This value and the sampling of the variable thermophily index of different alignments of protein sequences from mesophile, thermophile and hyperthermophile species make it possible to establish, with an extremely high statistical confidence, that the late stage of genetic code structuring took place in a hyperthermophile (or thermophile) 'organism'. Moreover the 95% confidence interval of the temperature at which the genetic code was fixed turned out to be 91+/-24 degrees C. These observations seem to support the hypothesis that the origin of life might have taken place at a high temperature.

Algorithms↗

The biological effects of solar activity.

The synchronization of biological circadian and circannual rhythms is broadly viewed as a result of photic solar effects. Evidence for non-photic solar effects on biota is also slowly being recognized. The ultrastructure of cardiomyocytes from rabbits, the time structure of blood pressure and heart rate of neonates, and the heart rate variability of human adults on earth and in space were examined during magnetically disturbed and quiet days, as were morbidity statistics. Alterations in both the about-daily (circadian) and about-weekly (circaseptan) components are observed during disturbed vs. quite days. The about-weekly period of neonatal blood pressure correlates with that of the local geomagnetic disturbance index K. Circaseptans which are seen early in human life and in various other forms of life, including unicells, may provide information about the possible site(s) of life's origins from an integrative as well as adaptive evolutionary perspective.

Animals↗

Evolution-driving genes.

Genomic sequences provide evidence for a common origin of life and its evolution via selection of genetic variants created by mutation and recombination. Two classes of genes are known to accelerate mutation and/or recombination rates in bacterial populations: stress-inducible wild-type genes, usually part of the SOS regulon, and genes whose functional loss, or downregulation, increases the rate of genetic variability (mutator and/or hyper-rec mutants).

Bacteria↗