Origin of Informational Polymers: The Concurrent Roles of Formamide and Phosphates

Physics of Life Reviews

et al. 2012

Self Cite

254

234

The complexity of life boils down to the definition: "self-sustained chemical system capable of undergoing Darwinian evolution" (Joyce, 1994) [1]. The term "self-sustained" implies a set of chemical reactions capable of harnessing energy from the environment, using it to carry out programmed anabolic and catabolic functions. We briefly present our opinion on the general validity of this definition.Running anabolic and catabolic functions entails complex chemical information whose stability, reproducibility and evolution constitute the core of what is dubbed genetics.Life as-we-know-it is made of the intimate interaction of metabolism and genetics, both built around the chemistry of the most common elements of the Universe (hydrogen, oxygen, nitrogen, carbon). Other elements like phosphorus and sulphur play important but ancillary and potentially replaceable roles.The reproducible interaction of metabolic and genetic cycles results in the hypercycles of organization and de-organization of chemical information that we consider living entities. In order to approach the problem of the origin of life it is therefore reasonable to start from the assumption that both metabolism and genetics had a common origin, shared a common chemical frame, were embedded in physical-chemical conditions favourable for the onset of both.The most abundant three-atoms organic compound in interstellar environment is hydrogen cyanide HCN, the most abundant three-atoms inorganic compound is water H 2 O. The combination of the two results in the formation of formamide H 2 NCOH. We have explored the chemistry of formamide in conditions compatible with the synthesis and the stability of compounds of potential pre-genetic and pre-metabolic interest. We discuss evidence showing (i) that all the compounds necessary for the build-up of nucleic acids are easily obtained abiotically, (ii) that essentially all the steps leading to the spontaneous generation of RNA are abiotically possible, (iii) that the key compounds of extant metabolic cycles are obtained in the same chemical frame, often in the same test tube.How close are these observations to a plausible scenario for the origin of life?

Section: Syntheses Of Nucleic Bases From Formamidementioning

confidence: 66%

Formamide and the origin of life

Saladino

Crestini

Physics of Life Reviews

et al. 2012

Self Cite

254

234

“…The open nucleotides 5Ј-AMP, 3Ј-AMP, and 2Ј-AMP were also tested in water at temperatures between 40 and 90°C. A number of additional variables were analyzed: concentration, time, addition of formamide (from 0 to 100%), presence of several minerals known to catalyze phosphorylation (5) or to increase the half-life of nucleic polymers (11,(13)(14)(15) 32 P]-ATP by T4 polynucleotide kinase, and the products were characterized by gel electrophoresis, allowing detailed evaluation of the lower sized oligomers.…”

Section: Resultsmentioning

confidence: 99%

Generation of Long RNA Chains in Water

Costanzo

Journal of Biological Chemistry

Ciciriello

et al. 2009

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119

138

The synthesis of RNA chains from 3,5-cAMP and 3,5-cGMP was observed. The RNA chains formed in water, at moderate temperatures (40 -90°C), in the absence of enzymes or inorganic catalysts. As determined by RNase analyses, the bonds formed were canonical 3,5-phosphodiester bonds. The polymerizations are based on two reactions not previously described: 1) oligomerization of 3, 5-cGMP to ϳ25-nucleotide-long RNA molecules, and of 3,5-cAMP to 4-to 8-nucleotide-long molecules. Oligonucleotide A molecules were further extended by reciprocal terminal ligation to yield RNA molecules up to >120 nucleotides long and 2) chain extension by terminal ligation of newly polymerized products of 3,5-cGMP on preformed oligonucleotides. The enzyme-and template-independent synthesis of long oligomers in water from prebiotically affordable precursors approaches the concept of spontaneous generation of (pre)genetic information.The origin of informational polymers is not understood. The RNA polymerization process has been studied for five decades, the results showing that from preactivated precursors polymers of several tens can be obtained, as reviewed previously (1). These pioneering studies provide the proof-of-principle that RNA precursors can self-assemble yielding linear polymers. However, the prebiotic validity of a process based on complex preactivation procedures is limited (1, 2), and the problem of defining a prebiotically plausible chemical and thermodynamic scenario for the synthesis and accumulation of informational polymers remains open. The core of the problem is the standard state Gibbs free energy change (3, 4) stating that condensation reactions are very inefficient in water. Given that extant polymerizations occur in water, this is a major difficulty, only partially solved by the fact that these processes at present occur inside the active site of enzymes where water activity may be drastically reduced. The other part of the extant solution, fruit of evolution, is the use of biologically highly preactivated triphosphate nucleotides (3). In primordia, RNA molecules had no enzymes to catalyze their chain-wise growth, and highly activated precursors can be considered as prebiotic only with difficulty.We reasoned that for a pre-enzymatic polymerization to occur the solution must have relied on a simple and robust process. Ideally, such a process should have been based on compounds that were reactive yet relatively stable, chemically not too elaborate to allow their efficient production, and not too dissimilar from the products of their polymerization to minimize the chemical cost of the process.It was observed that phosphorylation of nucleosides occurs in formamide simply in the presence of a source of organic or inorganic phosphate at temperatures at which both the reactants and the products are stable (5). Phosphorylation occurs in every possible position of the nucleoside sugar moiety resulting, both for purine and pyrimidine nucleosides, in the production of 2Ј-, 3Ј-, 5Ј-, 2Ј,3Ј-cyclic, and 3Ј,5Ј-cyclic XMPs 3 (5). Th...

“…The reaction is low yielding, but nevertheless, it shows that, although inefficient, RNA may generate itself from prebiotic precursors [18][19][20]. The conditions for self-polymerization of cyclic pyrimidine nucleotides have not been determined, yet.…”

Section: Introductionmentioning

confidence: 99%

Ribozyme Activity of RNA Nonenzymatically Polymerized from 3′,5′-Cyclic GMP

Costanzo

Giorgi

et al. 2013

Entropy

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3′,5′-Cyclic GMP spontaneously nonenzymatically polymerizes in a base-catalyzed reaction affording G oligonucleotides. When reacted with fully or partially sequence-complementary RNA (oligo C), the abiotically generated oligo G RNA displays a typical ribozyme activity consisting of terminal ligation accompanied by cleavage of an internal phosphate site of the donor oligonucleotide stem upon attack of the acceptor 3′ terminal OH. This reaction is dubbed Ligation following Intermolecular Cleavage (LIC). In a prebiotic perspective, the ability of oligo G polynucleotides to react with other sequences outlines a simple and possible evolutionary scenario based on the autocatalytic properties of RNA.