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At least 145 records · Page 8

Assembly of catalytic complexes from randomized oligonucleotides

The early evolution of life relied on catalytic RNAs (ribozymes) for central functions. To test whether early catalysts could have assembled from multiple short nucleic acid fragments in random sequence environments, we performed an in vitro selection from a short RNA library in the presence of 256 different DNA 20-nucleotide oligomers. High-throughput sequencing and biochemical analysis showed that most of the selected 1331 RNA sequences required at least one DNA for activity. Representatives for four of six RNA clusters that depended on DNA cofactors were active even when the 256 DNAs were replaced by completely random DNA 20-nucleotide oligomers. The formation of these catalytic complexes and the recruitment of oligonucleotide cofactors from completely random libraries demonstrate an important principle for the emergence of the earliest oligonucleotide catalysts.

Xu Han↗

Malate dehydrogenases. I.

Molecular sizes of diphosphopyridine nucleotide linked dehydrogenases of representative animal, plant and microbial species

BIOCHEMISTRY↗

Scaling features of noncoding DNA

We review evidence supporting the idea that the DNA sequence in genes containing noncoding regions is correlated, and that the correlation is remarkably long range--indeed, base pairs thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene, and utilize this fact to build a Coding Sequence Finder Algorithm, which uses statistical ideas to locate the coding regions of an unknown DNA sequence. Finally, we describe briefly some recent work adapting to DNA the Zipf approach to analyzing linguistic texts, and the Shannon approach to quantifying the "redundancy" of a linguistic text in terms of a measurable entropy function, and reporting that noncoding regions in eukaryotes display a larger redundancy than coding regions. Specifically, we consider the possibility that this result is solely a consequence of nucleotide concentration differences as first noted by Bonhoeffer and his collaborators. We find that cytosine-guanine (CG) concentration does have a strong "background" effect on redundancy. However, we find that for the purine-pyrimidine binary mapping rule, which is not affected by the difference in CG concentration, the Shannon redundancy for the set of analyzed sequences is larger for noncoding regions compared to coding regions.

Non-NASA Center↗

Statistical properties of DNA sequences

We review evidence supporting the idea that the DNA sequence in genes containing non-coding regions is correlated, and that the correlation is remarkably long range--indeed, nucleotides thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the "non-stationarity" feature of the sequence of base pairs by applying a new algorithm called detrended fluctuation analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and non-coding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to every DNA sequence (33301 coding and 29453 non-coding) in the entire GenBank database. Finally, we describe briefly some recent work showing that the non-coding sequences have certain statistical features in common with natural and artificial languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts. These statistical properties of non-coding sequences support the possibility that non-coding regions of DNA may carry biological information.

Non-NASA Center↗

A definition of the domains Archaea, Bacteria and Eucarya in terms of small subunit ribosomal RNA characteristics

The number of small subunit rRNA sequences is now great enough that the three domains Archaea, Bacteria and Eucarya (Woese et al., 1990) can be reliably defined in terms of their sequence "signatures". Approximately 50 homologous positions (or nucleotide pairs) in the small subunit rRNA characterize and distinguish among the three. In addition, the three can be recognized by a variety of nonhomologous rRNA characters, either individual positions and/or higher-order structural features. The Crenarchaeota and the Euryarchaeota, the two archaeal kingdoms, can also be defined and distinguished by their characteristic compositions at approximately fifteen positions in the small subunit rRNA molecule.

NASA Program Exobiology↗

Long-range correlation properties of coding and noncoding DNA sequences: GenBank analysis

An open question in computational molecular biology is whether long-range correlations are present in both coding and noncoding DNA or only in the latter. To answer this question, we consider all 33301 coding and all 29453 noncoding eukaryotic sequences--each of length larger than 512 base pairs (bp)--in the present release of the GenBank to dtermine whether there is any statistically significant distinction in their long-range correlation properties. Standard fast Fourier transform (FFT) analysis indicates that coding sequences have practically no correlations in the range from 10 bp to 100 bp (spectral exponent beta=0.00 +/- 0.04, where the uncertainty is two standard deviations). In contrast, for noncoding sequences, the average value of the spectral exponent beta is positive (0.16 +/- 0.05) which unambiguously shows the presence of long-range correlations. We also separately analyze the 874 coding and the 1157 noncoding sequences that have more than 4096 bp and find a larger region of power-law behavior. We calculate the probability that these two data sets (coding and noncoding) were drawn from the same distribution and we find that it is less than 10(-10). We obtain independent confirmation of these findings using the method of detrended fluctuation analysis (DFA), which is designed to treat sequences with statistical heterogeneity, such as DNA's known mosaic structure ("patchiness") arising from the nonstationarity of nucleotide concentration. The near-perfect agreement between the two independent analysis methods, FFT and DFA, increases the confidence in the reliability of our conclusion.

Non-NASA Center↗

Theoretical foundations for a quantitative approach to paleogenetics. I, II.

It is shown that by neglecting the phenomena of multiple hits, back mutation, and chance coincidence errors larger than 100% can be introduced in the calculated value of the average number of nucleotide base differences to be expected between two homologous polynucleotides. Mathematical formulas are derived to correct quantitatively for these effects. It is pointed out that the effects change materially the quantitative aspects of phylogenics, such as the length of the legs of the trees. A number of problems are solved without approximation.-

Holmquist, R.↗

Prebiotic phosphorylation of thymidine at 65 C in simulated desert conditions.

The phosphorylation of thymidine is described for a variety of conditions at 65 C to demonstrate that the reaction could readily take place in deserts at the present time. This might be used as an indication that urea-phosphate mixtures could have been important as phosphorylating agents on the primitive earth. Reaction products were identified by comparing their chromatographic and electrophoretic mobilities with those of authentic materials and by enzymatic degradation. The results show that good yields of nucleotides are obtained when nucleosides are heated with urea-phospate mixtures at 65 C. Reactions proceed more rapidly at moderate humidities than in a stream of dry nitrogen. Occasional wetting results in even faster and more extensive reactions. There was no reaction for a mixture of urea and trimetaphosphate.

Bishop, M. J.↗

Chemical evolution - Recent syntheses of bioorganic molecules.

Review of the important developments that have occurred in abiological biomonomer and biopolymer synthesis since about 1967, and discussion of their significance for the field of chemical evolution and the origin of life. The major portion of the review is devoted to important developments in the abiotic formation of bioorganic monomers and their condensation to biopolymers under conditions presumed to have prevailed on the primeval earth. Special attention is given to contributions shedding light on the mechanism of synthesis and selection of amino acids and on interactions of amino acids and polypeptides with nucleotides and oligonucleotides.

Stephen-Sherwood, E.↗

Prebiotic activation processes.

Questions regarding the combination of amino acids and ribonucleotides to polypeptides and polynucleotides are investigated. Each of the reactions considered occurs in the solid state in plausible prebiotic conditions. Together they provide the basis for a unified scheme of amino acid and nucleotide activation. Urea, imidazole and Mg(++) are essential catalytic components of the reaction mixtures. However, these compounds could probably be replaced by other organic molecules.

Lohrmann, R.↗

Studies related to primitive chemistry. A proton and nitrogen-14 nuclear magnetic resonance amino acid and nucleic acid constituents and a and their possible relation to prebiotic

Preliminary proton nuclear magnetic resonance (NMR) studies were made to determine the applicability of this technique for the study of interactions between monomeric and polymeric amino acids with monomeric nucleic acid bases and nucleotides. Proton NMR results for aqueous solutions (D2O) demonstrated interactions between the bases cytosine and adenine and acidic and aromatic amino acids. Solutions of 5'-AMP admixed with amino acids exhibited more complex behavior but stacking between aromatic rings and destacking at high amino acids concentration was evident. The multisite nature of 5'-AMP was pointed out. Chemical shift changes for adenine and 5'-AMP with three water soluble polypeptides demonstrated that significant interactions exist. It was found that the linewidth-pH profile of each amino acid is unique. It is concluded that NMR techniques can give significant and quantitative data on the association of amino acid and nucleic acid constituents.

Manatt, S. L.↗

Ultraviolet selection pressure on the earliest organisms

It had been proposed by Sagan (1957, 1961) that UV light, partially penetrating the primitive reducing atmosphere of the earth, posed a major problem for the earliest evolution of life. This argument is now updated and refined. The picture of a secondary reducing atmosphere is presented. It is assumed that an excess of hydrogen from this atmosphere has already escaped to space. The genetic material surrounded itself as a solution to the UV selection pressure with bases or nucleotides having no function whatever in replication or protein synthesis.

Sagan, C.↗

The prebiotic synthesis of oligonucleotides

This paper is primarily a review of recent developments in the abiotic synthesis of nucleotides, short chain oligonucleotides, and their mode of replication in solution. It also presents preliminary results from this laboratory on the prebiotic synthesis of thymidine oligodeoxynucleotides. A discussion, based on the physicochemical properties of RNA and DNA oligomers, relevant to the molecular evolution of these compounds leads to the tentative hypothesis that oligodeoxyribonucleotides of about 12 units may have been of sufficient length to initiate a self replicating coding system. Two models are suggested to account for the synthesis of high molecular weight oligomers using short chain templates and primers.

Oro, J.↗

Three-dimensional tertiary structure of yeast phenylalanine transfer RNA

Results of an analysis and interpretation of a 3-A electron density map of yeast phenylalanine transfer RNA. Some earlier detailed assignments of nucleotide residues to electron density peaks are found to be in error, even though the overall tracing of the backbone conformation of yeast phenylalanine transfer RNA was generally correct. A new, more comprehensive interpretation is made which makes it possible to define the tertiary interactions in the molecule. The new interpretation makes it possible to visualize a number of tertiary interactions which not only explain the structural role of most of the bases which are constant in transfer RNAs, but also makes it possible to understand in a direct and simple fashion the chemical modification data on transfer RNA. In addition, this pattern of tertiary interactions provides a basis for understanding the general three-dimensional folding of all transfer RNA molecules.

Kim, S. H.↗