The RNA World

Almost 20 years ago, in a review article in Nature, Gerald Joyce (1989) explained why RNA fulfils almost ah the conditions which a type of substance requires in order to be able to transfer information  

The matrix properties of RNA make the self-replication process easier. RNA matrices are able to control the synthesis of complementary oligonucleotides. 

Its ability to transfer information (see Sect. 6.4) and Catalytic properties (see Sect. 6.5) 

In ah of today s living systems, RNA is involved in processes which are very old from an evolutionary point of view. RNA occurs in protein biosynthesis in three different forms, and thus with three different functions tRNA, mRNA and rRNA. 

Most biochemically active coenzymes are either nucleotides or compounds which could be derived from nucleotides. 

Between 1981 and 1986, Thomas Cech and Sidney Altman discovered that there are at least two metabolic reactions where the catalysts are not proteins but RNAs. Up until then, it had been accepted that all enzymes are proteins, and normally the discovery of a few exceptions does not undermine a virtually universal rule, but those two examples had an extraordinary implication. 

In 1986, Walter Gilbert formulated it explicitly in these terms If there are two enzymic activities associated with RNA, there may be more. And if there are activities among these RNA enzymes, or rihozymes, that can catalyse the synthesis of a new RNA molecule from precursors and an RNA template, then there is no need for protein enzymes at the beginning of evolution. One can contemplate an RNA world, containing only RNA molecules that serve to catalyse the synthesis of themselves.  

The experimental data that we have today are not yet conclusive, if taken one by one, but together they form a very strong case in favour of an early historical role of RNAs. There are five main facts that support this conclusion  

Collectively, these facts strongly suggest that RNAs had a leading role in what here has been called postchemical evolution. It must be underlined, however, that RNAs are sophisticated, evolutionarily advanced molecules (Miller, 1987 Joyce, 1989 Orgel, 1992), and all the above facts do not allow us to conclude that they were also leading players in the earlier phase of chemical evolution. 

The fact that ribozymes came before protein enzymes does not mean that replication came before metabolism, but it is an historical fact that this is precisely the meaning that was given, almost universally, to the discovery of ribozymes. With very few exceptions, the RNA world has been interpreted with the logic of the replication paradigm if RNAs could behave as genes and as enzymes, then they did it immediately, at the very beginning, and became the first replicators in the history of life. 

Melting temperatures (Tm /°C) and free energies (-AG°37 /kJ) for duplexes with all possible combinations of 2 -hydroxyl and C-5 methyl groups. 

The melting temperature and free energy differences are also separated into methyl and 2 -OH effects. Conditions 4.5 pM NaCl, 10 mM MgCl2,10 mM Na PIPES, pH 5.5. Error limits for individual measurements are estimated at 0.5 °C in 7 m and 10 % in free energy. Third-strand transition coincides with duplex transition. Adapted from Reference [27]. 

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The discovery of nbozymes (Section 28 11) in the late 1970s and early 1980s by Sidney Altman of Yale University and Thomas Cech of the University of Colorado placed the RNA World idea on a more solid footing Altman and Cech independently discovered that RNA can catalyze the formation and cleavage of phosphodiester bonds—exactly the kinds of bonds that unite individual ribonucleotides in RNA That plus the recent discovery that ribosomal RNA cat alyzes the addition of ammo acids to the growing peptide chain in protein biosynthesis takes care of the most serious deficiencies in the RNA World model by providing precedents for the catalysis of biologi cal processes by RNA... 

Gesteland RF, Cech TR, Atkins JF (1999) The RNA World The nature of modern RNA suggests a Prebiotic RNA, 2nd ed., Cold Spring Harbor Laboratory Press, New York. 

This definition was previously used by Horowitz and Miller (1962). An undefined external energy source was included in this definition. The growing influence of the RNA world can be seen in the second NASA definition ... 

Fig. 1.5 Schematic representation of the evolution of life from its precursors, on the basis of the definition of life given by the authors. If bioenergetic mechanisms have developed via autonomous systems, the thermodynamic basis for the beginning of the archiving of information, and thus for a one-polymer world such as the RNA world , has been set up. Several models for this transition have been discussed. This phase of development is possibly the starting point for the process of Darwinian evolution (with reproduction, variation and heredity), but still without any separation between genotype and phenotype. According to the authors definition, life begins in exactly that moment when the genetic code comes into play, i.e., in the transition from a one-polymer world to a two-polymer world . The last phase, open-ended evolution, then follows. After Ruiz-Mirazo et al. (2004)...

It remains an open question as to whether this newly identified species of amino acid was important in the construction of peptide nucleic acids (see Sect. 6.7) in the prebiotic chemistry of the RNA world phase of biogenesis (Meierheinrich et al 2004). 

All this makes it clear that the discussions on pyrimidine synthesis are by no means over. The question is whether there was an RNA world or not. Recently, attempts have been made to bypass this problem by postulating a phase of development before the RNA world a pre-RNA world (see Sect. 6.7). But this is also hypothetical ... 

However, there are also biogenesis models which do not require phosphate, such as the inorganic hypothesis of the origin of life proposed by Cairns-Smith (see Sect. 7.1), the thioester world proposed by de Duve (see Sect. 7.4) or the sulphur-iron world suggested by Wachtershauser (see Sect. 7.3). The RNA world (see Chap. 6), however, cannot exist without phosphate. 

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. 

In today s discussion of the origin of life, the RNA World (Chapter 6) is seen as much more important, and is much better publicized, than the protein world . However, nucleic acids and proteins are of equal importance for the vital metabolic functions in today s life forms. Peptides and proteins are constructed from the same building blocks (monomers), the aminocarboxylic acids (generally known simply as amino acids). The way in which the monomers are linked, the peptide bond, is the same in peptides and proteins. While peptides consist of only a few amino acids (or to be more exact, amino acid residues), proteins can contain many hundreds. The term protein (after the Greek proteuein, to be the first) was coined by Berzelius in 1838. 

Even its proponents do not always discuss the RNA world in the same terms. However, there are three basic assumptions on which there is consensus (Joyce and Orgel, 1999) ... 

During the development phase of the RNA world, there were no functioning processes which were influenced by protein catalysts. 

The differences between the different versions of the RNA world mainly concern the questions ... 

Which complex mechanisms were active in the RNA world ... 

In spite of all the enthusiasm for the RNA world, critical observers point out (as do Joyce and Orgel in 1989) that the RNA world is only a hypothesis It has, however, led to the development of a series of interesting biogenesis models. Some points have been verified by means of successful experiments, but the hypothesis poses questions to which we have no answers at present (see Sect. 6.6). 

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 ... 

An introduction to the method of in vitro evolution is given by Wilson and Stoszak (1999). The RNA lipase ribozyme, with about 140 nucleotides (but without the pyrimidine base cytosine), folded in a defined structure and was able to reach a reaction rate 105 times higher than in the uncatalysed reaction. This result certainly surprised those biogenesis researchers who were critical of the RNA world but we do not know whether the result changed their attitude to it ... 

The RNA world has its critics as well as its proponents. A third group is formed by the soft critics , who warn of too much optimism one of these is Leslie Orgel, an expert on the problems involved, who made it quite clear that the RNA world is a hypothesis and nothing more. 

An article by Dworkin, Lazcano and S. Miller in the Journal of Theoretical Biology shows how much is still unclear in the search for the first informationtransferring species on Earth. The authors assume the RNA world to be a... 

The considerable problems associated with the RNA world led to a search for simpler systems. Nelson et al. (2000a, b) sum up the greatest problems of the theory as follows ... 

A majority of biogenesis researchers seem to accept the RNA world, in spite of the many unanswered questions a world in which protein synthesis, coded by nucleic acids and catalysed by ribosomes, did not yet occur. Leslie Orgel, probably the most profound connoisseur of this difficult metier, calls attention to important consequences which follow from acceptance of the RNA world. In summary, Orgel discusses two possibilities ... 

The RNA world was the first biological world. If this is the case, we can learn or predict but little about the prebiotic chemistry of the RNA world from the biochemistry of today perhaps only the fact that the formation and polymerisation of nucleotides were once prebiotic processes. Thus Orgel is not of the... 

The RNA world was not the first biological world. In this case, the conclusions drawn above are not justified. We can then speculate that the monomers of an early genetic polymer can still be recognized today as important biochemical substances. Orgel considers it unlikely that RNA could have been formed prebiotically ribonucleotides are too complex to have evolved on the primeval Earth in sufficient amounts, and with sufficient purity. 

The idea of takeover many biogeneticists are of the opinion that the RNA world must have had a simpler precursor pre-RNA world . 

The presence of other worlds , such as the RNA world or the clay crystal world. 

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