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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
NASA NTRS1975

Stereomolecular interactions and microsystems in experimental protobiogenesis

A theory on the origin of the first reproducing (in the sense of Fox, 1973) cells on earth is presented. A degree of self-ordering has been observed in the selective thermal reactions of certain ones of the amino acids which have been found in samples of meteorites, lunar samples, and terrestrial lava, and which have been synthesized from formaldehyde and ammonia under conditions modeling those assumed to have been present in the primitive earth. The genetic code is supposed to have arisen from a nonrandom matrix of preproteins. The ordering of preproteins specified limitations in the identity of the pre-enzymes and primordial microsystems which gave rise to contemporary living systems. The evolution of progresively more complex system was largely determined by stereochemical forces involving the shapes of the molecules themselves and the regulatory effects of the confines of the microsystems.

Fox, S. W.↗
NASA NTRS1975

Prebiotic polynucleotides and polypeptides

Work on the nonenzymatic replication of polynucleotides is discussed emphasizing sequence dependence and showing that alternating polynucleotides should replicate more easily than any others. Experimental work is described showing that polypeptides in which hydrophobic and hydrophilic residues alternate, adopt a beta structure in aqueous solution. The possible relevance of these observations for the evolution of the genetic code is given.

Orgel, L. E.↗
NASA NTRS1978

Evaluation of compositional nonrandomness in proteins

The finite sampling component of Q, a measure of nonrandomness in the amino acid composition of proteins, is quantitatively estimated by using the natural abundances of amino acids rather than the genetic code table frequencies, and the revised value of Q implies that the value of Q(c), a measure of selective effects above and beyond those imposed by the average natural abundance of the amino acids, should be 9.7 rather than its previous value of 24.3. Individual Q(c) values are given for 81 protein families. The standard deviation of the population of Q(c) values is 12.5 but the Q(c) value differs significantly from the value of zero expected were the natural abundances of the amino acids the only selective constraint. The small value of Q(c) indicates that quantitatively minimal adjustments away from the average protein composition are necessary to maintain many different biological functions.

Holmquist, R.↗
NASA NTRS1979

Selective formation of microparticles by homopolyribonucleotides and proteinoids rich in individual amino acis

The formation of phase-separated microparticles following the mixing of solutions of homopolyribonucleotides with solutions of several basic thermal proteinoids, each rich in an individual amino acid, has been studied. Three of the 4 proteinoids studied yielded results consistent with a matrix of anticodonicity; the fourth did not. The meaning of these results, and others, relative to a postulated matrix for the genetic coding mechanism is discussed.

Lacey, J. C., Jr.↗
NASA NTRS1981

Enhancement of peptide bond formation by polyribonucleotides on clay surfaces in fluctuating environments

The selective effects of polyribonucleotides on the formation of glycine peptide bonds in glycine on clay surfaces are investigated as a model for a template mechanism for the effects of polynucleotides on peptide bond formation. Free oligoglycine yields were determined for the cycling reaction of glycine in the presence and absence of clay and polyribonucleotides or polydeoxyribonucleotides. The polyribonucleotides are observed to lead to increases of up to fourfold increases in oligoglycine formed, with greater enhancements for poly-G nucleotides than for poly-A, poly-U and poly-C, indicating a codonic bias. Polydeoxyribonucleotides are found to provide no enhancement in peptide formation rates, and yields were also greatly reduced in the absence of clay. A mechanism for peptide synthesis is proposed which involves the activation of glycine on the clay surface, followed by the formation of esters between glycine and the 2-prime OH groups of the polyribonucleotide and peptide bonds between adjacent amino acyl esters. It is pointed out that if this mechanism is correct, it may provide a basis for a direct template translation process, which would produce a singlet genetic code.

White, D. H.↗
NASA NTRS1981

Origins of the protein synthesis cycle

Largely derived from experiments in molecular evolution, a theory of protein synthesis cycles has been constructed. The sequence begins with ordered thermal proteins resulting from the self-sequencing of mixed amino acids. Ordered thermal proteins then aggregate to cell-like structures. When they contained proteinoids sufficiently rich in lysine, the structures were able to synthesize offspring peptides. Since lysine-rich proteinoid (LRP) also catalyzes the polymerization of nucleoside triphosphate to polynucleotides, the same microspheres containing LRP could have synthesized both original cellular proteins and cellular nucleic acids. The LRP within protocells would have provided proximity advantageous for the origin and evolution of the genetic code.

Fox, S. W.↗
NASA NTRS1982

The updated experimental proteinoid model

The experimental proteinoid model includes new results indicating that polymers sufficiently rich in basic amino acid catalyze the synthesis of peptides from ATP and amino acids and of oligonucleotides from ATP. The need for simulation syntheses of amino acids yielding significant proportions of basic amino acids is now in focus. The modeled simultaneous protocellular synthesis of peptides and polynucleotides is part of a more comprehensive proposal for the origin of the coded genetic mechanism. The finding of membrane and action potentials in proteinoid microspheres, with or without added lecithin, is reported. The crucial nature of a nonrandom matrix for protocells is developed.

Fox, S. W.↗
NASA NTRS1983

Complexes of polyadenylic acid and the methyl esters of amino acids

A study of amino acid methyl esters binding to polyadenylic acid supports the theory that the genetic code originated through weak but selective affinities between amino acids and nucleotides. NMR, insoluble complex analysis, and ultraviolet spectroscopy are used to illustrate a correlation between the hydrophybicities of A amino acids and their binding constants, which, beginning with the largest, are in the order of Phe (having nominally a hydrophobic AAA anticodon), Ile, Leu, Val and Gly (having a hydrophilic anticodon with no A). In general, the binding constants are twice the values by Reuben and Polk (1980) for monomeric AMP, which suggests that polymer amino acids are interacting with only one base. No real differences are found betwen poly A binding for free Phe, Phe methyl ester or Phe amide, except that the amide value is slightly lower.

Khaled, M. A.↗
NASA NTRS1985

Search for the Universal Ancestors

By its nature, the study of the origins of life is multidisciplinary, requiring contributions from astronomers, biologists, chemists, geologists, physicists, and many others. Partial answers are provided to many questions about organic chemical evolution and the origin of life. It is observed that the gaps in our knowledge concerning the steps from the nonliving to the living are numerous. Among these gaps are: (1) a solar system formation with its accumulation of raw materials; (2) the synthesis of the life forming monomers, such as the amino acids, nucleotides, and lipids; (3) the condensation of these monomers into useful polymers, such as proteins and nucleic acids; (4) the sequestering of these materials into droplets of proteinoid or membrane-like structures; and (5) the development of a chemical memory (the genetic code) to pass on to the progeny the information acquired.

Hartman, H.↗
NASA NTRS1986

RNA catalysis and the origins of life

The role of RNA catalysis in the origins of life is considered in connection with the discovery of riboszymes, which are RNA molecules that catalyze sequence-specific hydrolysis and transesterification reactions of RNA substrates. Due to this discovery, theories positing protein-free replication as preceding the appearance of the genetic code are more plausible. The scope of RNA catalysis in biology and chemistry is discussed, and it is noted that the development of methods to select (or predict) RNA sequences with preassigned catalytic functions would be a major contribution to the study of life's origins.

Orgel, Leslie E.↗
NASA NTRS1991

Macromolecular recognition: Structural aspects of the origin of the genetic system

Theoretical simulation of prebiotic chemical processes is an invaluable tool for probing the phenomenon of evolution of life. Using computational and modeling techniques and guided by analogies from present day systems we, seek to understand the emergence of genetic apparatus, enzymatic catalysis and protein synthesis under prebiotic conditions. In one possible scenario, the RNA enzymatic reaction plays a key role in the emergence of the self-replicating and offers a clue to the onset of enzymatic catalysis prior to the existence of the protein biosynthetic machinery. Our ultimate goal is to propose a simple RNA segment which contains the specificity and catalytic activity of the contemporary RNA enzyme and which could emerge in a primordial chemical environment. To understand the mechanism of ribozyme catalyzed reactions, ab initio and semi-empirical (ZINDO) programs were used to investigate the reaction path of transphosphorylation. A special emphasis was placed on the possible catalytic and structural roles played by the coordinated magnesium cation. Both the inline and adjacent mechanisms of transphosphorylation have been studied. Another important aspect of this reaction is the identity of the functional groups which are essential for the acid base catalysis. The structural characteristics of the target helices, particularly a possible role of G center dot T pair, is under examination by molecular dynamics (MD) simulation technique. Modeling of the ancestral aminoacyl-tRNA synthetases (aRS) may provide important clues to the emergence of the genetic code and the protein synthetic machinery. Assuming that the catalytic function evolved before the elements of specific recognition of a particular amino acid, we are exploring the minimal structural requirements for the catalysis of tRNA aminoacylation. The molecular modeling system SYBYL was used for this study based on the high resolution crystallographic structures of the present day tyrosyl-adenylate:tyrRS and tRNA(Gln): ATP:glnRS complexes. The trinucleotide CCA of the 3'-end tRNA is placed into the active site pocket of tyrRS, based on the scheme of interaction between tRNA(Gln) and glnRS, and upon the stereochemistry of the tyrRS:tRNA:Tyr-AMP transition state. This provides a model of the non-specific recognition of a tRNA's 3'-end by an aRS, which might be similar to that of the ancestral aRS's. In the next step, modeling of the rest of the acceptor stem of tRNA (Tyr) with tyrRS is carried out.

Rein, Robert↗
NASA NTRS1991

Macromolecular recognition: Structural aspects of the origin of the genetic system

Theoretical simulation of prebiotic chemical processes is an invaluable tool for probing the phenomenon of the evolution of life. Using computational and modeling techniques and guided by analogies from present day systems, we seek to understand the emergence of the genetic apparatus, enzymatic catalysis and protein synthesis under prebiotic conditions. Modeling of the ancestral aminoacyl-tRNA-synthetases (aRS) may provide important clues to the emergence of the genetic code and the protein synthetic machinery. The minimal structural requirements for the catalysis of tRNA aminoacylation are being explored. A formation of an aminoacyl adenylate was studied in the framework of ab initio molecular orbital theory. The role of individual residues in the vicinity of the TyrRS active site was examined, and the effect of all possible amino acids substitutions near the active site was examined. A formation of aminoacyl tRNA was studied by the molecular modeling system SYBYL with the high resolution crystallographic structures of the present day tRNA, aRS's complexes. The ultimate goal is to propose a simple RNA segment that is small enough to be build in the primordial chemical environment but maintains the specificity and catalytic activity of the contemporary RNA enzyme. To understand the mechanism of ribozyme catalyzed reactions, ab initio and semi-empirical (ZINDO) programs were used to investigate the reaction path of transphosphorylation. A special emphasis was placed on the possible catalytic and structural roles played by the coordinated magnesium cation. Both the inline and adjacent mechanisms of transphosphorylation were studied. The structural characteristics of the target helices, particularly a possible role for the G-T pair, is also studied by a molecular dynamics (MD) simulation technique.

Rein, Robert↗
NASA NTRS1994

ISSOL Meeting, 7th, Barcelona, Spain, July 4-9, 1993

The journal issue consists of abstracts presented at the International Society for the Study of the Origins of Life (ISSOL) conference. Topics include research on biological and chemical evolution including prebiotic evolution: cosmic and terrestrial; mechanisms of abiogenesis including synthesis and reactions of biomonomers; and analysis of cometary matter and its possible relationship to organic compounds on Earth. Theories and research on origins of ribonucleic acids (RNA), deoxyribonucleic acid (DNA), and other amino acids and complex proteins including their autocatalysis, replication, and translation are presented. Abiotic synthesis of biopolymers, mechanisms of the Genetic Code, precellular membrane systems and energetics are considered. Earth planetary evolution including early microfossils and geochemical conditions and simulations to study these conditions are discussed. The role of chirality in precellular evolution and the taxonomy and phylogeny of very simple organisms are reported. Past and future explorations in exobiology and space research directed toward study of the origins of life and solar system evolution are described.

Ferris, James P.↗
NASA NTRS1995

ISSOL Meeting, Barcelona, Spain, 1993

Topics in a conference on the origins of life and the evolution of the biosphere include the origin of chirality, prebiotic chemistry of small biomolecules, primitive polymer formation, RNA regulation and control. Early origins of life and the ecology of hydrothermal systems such as ocean floor vents and their simple organisms are examined. The process of mineral catalysis in Montmorillonite as a model for early metabolism is used. The origin of the genetic code and the development of branching in molecular structures of amino acids is described. Studies are reported of the effects of meteorite impact on early Earth life.

Ferris, James P.↗
NASA NTRS1994

Language in Comparative Perspective

The twentieth century will be noted for a wide variety of scientific and technological advancements, including powered flight, antibiotics, space travel, and the breaking of the genetic code. It also should be noted as the century in which major psychological, as well as biological, continuities between animal and human have been defined. Charles Darwin (1859) was quite right when he anticipated continuity in mental processes, some of which provide for language. Though none will argue that any animal has the full capacity of humans for language, none should deny that at least some animals have quite impressive competencies for language skills, including speech comprehension. The finding that the language skills in the bonobo and the chimpanzee are likely more fully and efficiently developed as a result of early rearing than by formal training at a later age declares a continuity even stronger than that defined by the language acquisition potential of the ape. To clarify, because early rearing facilitates the emergence of language in ape as well as in child, a naturalness to the familiar course of language acquisition, whereby comprehension precedes production, is also corroborated. In turn, the continuity and the shared naturalness of language acquisition serve jointly to define an advanced and critical point of linkage between the genera Pan and Homo - and, as concluded by Domjan (1993), one worthy of contributing to the series of reconceptions of ourselves as anticipated by Ploog and Melnechuk (1971).

Rumbaugh, Duane M.↗
NASA NTRS2009

Evolvable Neural Software System

The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

Curtis, Steven A.↗
NASA NTRS2012

The Origins of Transmembrane Ion Channels

Even though membrane proteins that mediate transport of ions and small molecules across cell walls are among the largest and least understood biopolymers in contemporary cells, it is still possible to shed light on their origins and early evolution. The central observation is that transmembrane portions of most ion channels are simply bundles of -helices. By combining results of experimental and computer simulation studies on synthetic models and natural channels, mostly of non-genomic origin, we show that the emergence of -helical channels was protobiologically plausible, and did not require highly specific amino acid sequences. Despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. Specifically, we explain how the antiamoebin channels, which are made of identical helices, 16 amino acids in length, achieve efficiency comparable to that of highly evolved channels. We further show that antiamoebin channels are extremely flexible, compared to modern, genetically coded channels. On the basis of our results, we propose that channels evolved further towards high structural complexity because they needed to acquire stable rigid structures and mechanisms for precise regulation rather than improve efficiency. In general, even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during evolution.

Pohorille, Andrew↗
NASA NTRS2016

Epigenetics Research on the International Space Station

The International Space Station (ISS) is a state-of-the orbiting laboratory focused on advancing science and technology research. Experiments being conducted on the ISS include investigations in the emerging field of Epigenetics. Epigenetics refers to stably heritable changes in gene expression or cellular phenotype (the transcriptional potential of a cell) resulting from changes in a chromosome without alterations to the underlying DNA nucleotide sequence (the genetic code), which are caused by external or environmental factors, such as spaceflight microgravity. Molecular mechanisms associated with epigenetic alterations regulating gene expression patterns include covalent chemical modifications of DNA (e.g., methylation) or histone proteins (e.g., acetylation, phorphorylation, or ubiquitination). For example, Epigenetics ("Epigenetics in Spaceflown C. elegans") is a recent JAXA investigation examining whether adaptations to microgravity transmit from one cell generation to another without changing the basic DNA of the organism. Mouse Epigenetics ("Transcriptome Analysis and Germ-Cell Development Analysis of Mice in Space") investigates molecular alterations in organ-specific gene expression patterns and epigenetic modifications, and analyzes murine germ cell development during long term spaceflight, as well as assessing changes in offspring DNA. NASA's first foray into human Omics research, the Twins Study ("Differential effects of homozygous twin astronauts associated with differences in exposure to spaceflight factors"), includes investigations evaluating differential epigenetic effects via comprehensive whole genome analysis, the landscape of DNA and RNA methylation, and biomolecular changes by means of longitudinal integrated multi-omics research. And the inaugural Genes in Space student challenge experiment (Genes in Space-1) is aimed at understanding how epigenetics plays a role in immune system dysregulation by assaying DNA methylation in immune cells directly in space using miniPCR technology. In addition, NASA's geneLAB campaign covers the epigenome as part of the "expressome", by employing an innovative open source science platform for multi-investigator high throughput utilization of the ISS. Earth benefits of Epigenetics research onboard the ISS range from contributions to the fundamental understanding of epigenetic phenomena with applications in countermeasure development for biomedical conditions, to the generation of integrated strategies for personalized medicine based on unique physiological responses.

Love, John↗