RNA-world hypothesis

The local conditions of temperature and pressure, as well as the new energy source in the form of the electrochemical gradient, can all be incorporated into the Gibbs free energy by adding new terms to the chemical potential. Variation of AG and AH with temperature are all standard thermodynamics, although we will resist the temptation to explore them here. 

There are many potential molecules and possible routes to the synthesis of biomolecules that might form the basis of a primitive metabolism but thus far we have not addressed the question of information propagation or Darwinian evolution. Information storage must be contained within a sequence, such as words in a sentence or the base sequences within the genetic code, and that requires a polymerisation reaction, which is preferably autocatalytic to reproduce the information accurately. Peptides and nucleotides have this property, although the condensation reaction joining them together needs to be activated. 

The theory that life began in an RNA World suggests that the first self-replicating system was a set of RNA molecules. The catalytic and informationtransferring properties of RNA indicate a possible scenario  

Relatively short RNA oligonucleotides were first formed by random events. 

Some oligonucleotides began to catalyse complementary copies by acting as templates. 

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The RNA world hypothesis then rekindled interest in the still open question of the origin of the phosphorus. How could acceptable synthetic routes to the nucleic acids be developed, if it was not even clear which phosphate derivatives were available on the primeval Earth An RNA world is not possible without reactive phosphates or similarly efficient phosphorus compounds Thus, the search for effective phosphorus or phosphate sources continued unabated. 

The RNA world hypothesis caused prebiotic phosphate chemistry to become an attractive research area again unfortunately, no clear evidence for a realistic nucleotide synthesis under the simplified conditions of a primitive Earth has yet appeared. Important work on nucleoside phosphorylation has, however, been done. It is important to distinguish between ... 

Compounds of crucial importance for the RNA world or a precursor phase could have been formed in this or similar ways. Thus, a thioester world seems to support the RNA world hypothesis, although de Duve can be considered as a careful critic of the latter hypothesis. His opinions were expressed in a short article in Nature under the provoking title Did God make RNA (de Duve, 1988). 

There are further theoretical objections to this RNA-world hypothesis, especially since we know of no organisms based on RNA without DNA and proteins. Moreover, RNA is not able to act as a catalyst for many essential simple molecule reactions, e.g. of CO, H2, N2, nor for most oxidation/reduction changes, and RNA... 

Conspicuously missing from this mixture is thymine, which led to the suggestion that RNA preceded DNA in what has become known as the RNA World hypothesis. 

RNA World hypothesis The early synthesis of purines and the observation of ribozyme autocatalysis lead to the idea of RNA preceding DNA... 

RNA World hypothesis The recognition that RNA can self-replicate leads to the idea that information propagation and the genetic code first started with RNA. 

Some consequences of the RNA world hypothesis. Orig. Life Evol. Biosph., 33, 211-18. 

The division of function between DNA (genetic information storage) and protein (catalysis) was, according to the RNA world hypothesis, a later development. New variants of self-replicating RNA molecules developed, with the additional ability to catalyze the condensation of amino acids into peptides. Occasionally, the peptide (s) thus formed would reinforce the self-replicating ability of the RNA, and the pair—RNA... 

The RNA world hypothesis requires a nucleotide polymer to reproduce itself. Can a ribozyme bring about its own synthesis in a template-directed manner The self-splicing rRNA intron of Tetrahymena (Fig. 26-26) catalyzes the reversible attack of a guanosine residue on the 5 splice junction (Fig. 26-37). If the 5 splice site and the internal guide sequence are removed from the intron, the rest of the intron can bind RNA strands paired with short oligonucleotides. Part of the remaining intact intron effectively acts as a template for the... 

A self-replicating polymer would quickly use up available supplies of precursors provided by the relatively slow processes of prebiotic chemistry. Thus, from an early stage in evolution, metabolic pathways would be required to generate precursors efficiently, with the synthesis of precursors presumably catalyzed by ri-bozymes. The extant ribozymes found in nature have a limited repertoire of catalytic functions, and of the ribozymes that may once have existed, no trace is left. To explore the RNA world hypothesis more deeply, we need to know whether RNA has the potential to catalyze the many different reactions needed in a primitive system of metabolic pathways. 

Diels-Alder cycloaddition is one of the central reactions in organic synthesis and, despite its minor biological significance, has often been used in innovative approaches in catalysis research. In the context of the RNA world hypothesis, the formation of carbon-carbon bonds would be essential in anabolic pathways. 

Nevertheless, the RNA World hypothesis would seem to answer most of the questions raised above how can an essentially linear molecule be autocatalytic, how can it synthesize proteins, and how can it replicate Autocatalysis can occur because RNA can adopt a wide range of secondary and tertiary structures that position RNA monomers into a preorganized sequence and link them together, it can apply the same flexibility to bind other small molecules and catalyse their polymerization, and it could form weakly interacting sense and antisense duplexes. The main problem is... 

The RNA world hypothesis provides a convenient focus for new experiments that will not only test its validity but will fundamentally advance our knowledge of nucleotide chemistry and RNA catalysis. Several critical experiments should more fully establish (or eliminate) the idea that the forebears of modem life were replicating RNA molecules. 

Santoro and Joyce (218). The last authors cited reported the selection of multipurpose RNA-cleaving DNAzymes with potential applications in molecular biology. The elusive RNA replicases, which should be able to replicate RNA structures including their own to sustain the RNA world hypothesis, are a common target for research a recent review (219) summarized the efforts in this field. 

Key to the Origin of Life - Ribozymes Ribozymes are nucleic acids with catalytic capabilities. The discovery of ribozymes led to the RNA world hypothesis for the origin of life. 

An RNA that exhibits enzyme-Hke activity is called a ribozyme. The discovery of ribozymes had a great impact on research into the origins of life. Identifying catalytic capabilities in RNA, an information molecule, led to a new theory the RNA world hypothesis. This suggests that RNA was the first life form on Earth, and when it first evolved it performed both catalytic and enzymatic functions. The natural selection process associated with evolution eventually caused the RNA to evolve into the highly sophisticated supramolecular systems observed in the complex life forms present today. 

Orgel LE (2003) Some consequences of the RNA World Hypothesis. Origins of life and Evolution of the Biosphere 33 211-218... 

The RNA world hypothesis proposes that RNA-based living systems predated current DNA-based life. Individual RNAs, which can store information like DNA and furthermore catalyze reactions virtually like protein enzymes, may have supported cellular and/or precellular life. The naturally occurring catalytic RNA molecules are highly specific such as the small subunit bacterial ribosomal RNA that is active as a RNA peptidyl transferase. In general, ribozymes seem to be relics from the RNA world. Many different synthetic ribozymes produced in the laboratory have diverse but defined specificities. The specificity of ribozymes is due to the intrinsic chiral centers of the RNA molecules of secondary and tertiary structure. The main evidence for an RNA world is the three essential RNA classes that act in concert to direct the specific and successive biosynthesis of proteins tRNA, rRNA, and mRNA. 

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