The RNA world hypothesis
The RNA world hypothesis is a theory that proposes the presence of life forms based exclusively on RNA (ribonucleic acid) before the formation of current living organisms based mainly on DNA (deoxyribonucleic acid).
According to this hypothesis, the current system including DNA and proteins would have evolved from the RNA world, which compared to RNA alone have considerable advantages in terms of stability and flexibility.
History
The term "RNA world" was used for the first time by the Nobel laureate Walter Gilbert in 1986 in a commentary article on the catalytic functions of numerous forms of RNA which, precisely in that period, began to be highlighted within the scientific community. In any case, the idea of a DNA- and protein-independent RNA life had already been formulated two decades earlier in Carl Woese's 1968 book The Genetic Code. However, such an idea had already been launched in 1963 by molecular biologist Alexander Rich, of the Massachusetts Institute of Technology, who spoke of it in an article inserted in a volume published in honor of the Nobel laureate Albert Szent-Györgyi.
The hypothesis and properties of RNA
According to the RNA world hypothesis, this macromolecule may have originally been solely responsible for cellular or pre-cellular life. Some theories relating to the origin of life present RNA-mediated information and catalysis as the first step in the evolution of cellular life. RNA is in fact able to store information but, compared to DNA, it is also able to catalyze reactions such as protein enzymes.
The hypothesis assumes that this RNA-based system would have evolved into the current system also including DNA and proteins thanks to the great chemical stability of the DNA (necessary for the conservation of the very precious gene information) and to the greater catalytic flexibility that amino acids guarantee. According to the RNA world hypothesis, therefore, the RNA still present in cells (in ribosomes and ribozymes) is only a residue of the original RNA world.
RNA as an enzyme
RNAs with enzyme function, or ribozyme, are possible although not common in today's DNA-based life. However, ribozymes play an important role; ribozymes are essential components of the ribosome, the latter being vital for protein synthesis. There are many possible functions of ribozyme: nature makes extensive use of self-splicing RNA, and direct evolution has created ribozymes with a variety of activities.
Among the most relevant catalytic properties relating to the origin of life we have:
- The ability to self-duplicate, or to duplicate other RNA molecules. Relatively short molecules of RNA capable of duplicating others have been produced in the laboratory. The shortest to be identified is 165 bases, although it is believed that even less may be enough. The most faithful, of 189 bases, showed an accuracy of 98.9%, which means in simple terms that, by replicating itself, it would be able to make an exact copy every eight attempts.
- The ability to catalyze simple chemical reactions, which makes it possible to create new molecules. Relatively short filaments with such capabilities were made in the laboratory.
- The ability to form peptide bonds and, therefore, short peptides. This operation is currently carried out by ribosomes, complexes made up of proteins and two long RNA molecules (known as rRNA) believed to be the main ones responsible for protein synthesis. In the laboratory, a molecule capable of making short peptides was synthesized. It can be hypothesized that current ribosomes may have evolved from such molecules. It has also been suggested that the amino acids may have been initially complexed with RNA molecules as cofactors capable of amplifying and diversifying enzymatic capacities; the mRNA could have evolved from similar molecules and the tRNA from filaments able to catalyze the transfer of the same amino acids towards the short peptides.
RNA in the conservation of information
RNA is a very similar molecule to DNA, with only two chemical differences. This similarity, for example, allows for the creation of mixed double helices of DNA and RNA. For this reason, it is possible to hypothesize a role in the conservation of information, typical of DNA, also for RNAs.
Comparison between the structure of DNA and RNA
The main difference between the molecules is the presence of a hydroxyl group in the 2 'position of the ribose present in the RNA molecule. This group forces ribose into the C3'-endo conformation, unlike the C2'-endo typical of deoxyribose, thus generating two molecules that are however different from each other. Most importantly, this group makes the molecule less stable, as it can attack the nearby phosphodiester bond and break it.
The other relevant difference is the RNA base set used, which includes uracil instead of the thymine used by DNA. These are similar molecules, although uracil requires less energy to be produced. From the pairing point of view, there are no relevant consequences: adenine is able to bind both bases indifferently. The real limitation of the use of uracil is that it can result from the deamination of cytosine, making RNA molecules particularly susceptible to mutations that replace base pairs such as GC with GU.
Limits in the conservation of information in RNA
Storing large amounts of information in RNA is not straightforward. The structure of RNA makes its long strands intrinsically fragile, which can undergo degradation through hydrolysis. The aromatic bases, which efficiently absorb UV radiation, are also very prone to structural modifications, which make the accuracy of this conservation very low. These limitations do not make it impossible for RNA to retain information. The presence of an optimized molecule such as DNA explains why RNA is not used for this purpose today, but does not exclude that this may have occurred in the primordial stages of life on Earth.
Value of the hypothesis
The properties of RNA make the presence of an RNA world conceptually possible, although its plausibility as an explanation of the origin of life is still widely debated.
A slightly different version of the hypothesis is that a different type of nucleic acid, called pre-RNA, was the first to appear as a molecule capable of self-replication, only to be subsequently replaced by RNA. These types of nucleic acid are sometimes more readily produced and / or polymerized under prebiotic conditions. Suggestions for these types of nucleic acid include PNA, TNA, or GNA.
Arguments in favor
The hypothesis is considered extremely likely due to the enormous versatility of the RNA molecule, capable of storing, transmitting and duplicating genetic information in a similar way to DNA but also, in addition, to act as a ribozyme and to catalyze reactions, as do protein enzymes. Although the nucleotides were not identified in the classic Miller-Urey experiment, there are other simulations, such as that of Joan Oro, which highlight their possible autonomous synthesis in the environmental conditions that characterized the origin of life. The hypothesis is also supported by studies on very simple ribozymes, such as viral Q-beta RNAs, which have shown self-replicative capabilities even under very important selective pressures.
Furthermore, the environmental conditions of the early Earth may have been ideal for a labile molecule like RNA. Ultraviolet rays, in fact, simultaneously induce the polymerization of RNA and the breakdown of other types of organic molecules potentially capable of catalyzing the degradation of RNA (such as ribonucleases). In any case, this is an aspect not yet corroborated by experimental observations.
Opposing arguments
The arguments contrary to the hypothesis are based on the extreme improbability of the spontaneous formation of RNA molecules, also supported by the fact that the cytosine base has not been sufficiently tested in prebiotic simulation methods, since it easily undergoes hydrolysis.
The prebiotic conditions necessary for the spontaneous formation of the three elements that make up a nucleotide are different from each other. The nitrogenous bases are formed in different environments than those necessary for the formation of the sugars present in the nucleic acid skeleton. For this reason, it would therefore be necessary to hypothesize a spontaneous synthesis of the two classes of molecules in separate environments, followed by a subsequent union. However, it must be said that, in an aqueous environment, such a union is unlikely, since nitrogenous bases and sugars are in any case unable to react. In anhydrous environment, purines are able to bind sugars (but only 8% at the correct carbon), while between pyrimidines and ribose there is no possibility of spontaneous binding even in a non-aqueous environment.
The third element, phosphate, is itself extremely rare in natural solutions, as it precipitates quickly. And even when present, it should combine with the nucleoside at the correct hydroxyl. In order to be able to insert itself into an RNA molecule, then, the nucleotide would have to activate itself through the binding of two other phosphate groups (to form, for example, adenosine triphosphate). In addition to all this, ribose must have the correct stereoisomerism, since nucleotides having incorrect chirality act as transcription terminators.
Even on the basis of considerations of this kind, Cairns-Smith criticized the exponents of the scientific community in 1982 for having exaggerated in drawing consequences from the Miller-Urey experiment. In fact, he argued that this experiment had not shown that nucleic acids were the basis of the origin of life, but simply that this hypothesis was not implausible. Cairns-Smith argued that, in order to reach the quantities of molecules necessary to give rise to life, the process of building nucleic acids would have to respect 18 autonomous conditions between them for several million years.
The RNA world in detail: mechanisms of prebiotic synthesis of RNA
The hypothesis assumes the presence in the primordial soup of nucleotides able to easily form chemical bonds between them and to break these bonds with the same probability, thanks to the low energy required for such events. In this environment, some base sequences having catalytic properties would have been able to amplify the formation of sequences with identical characteristics, thanks precisely to the catalytic activity capable of reducing the energy necessary for the formation of such sequences. The main consequence of the formation of such sequences would have been the fact that the production of RNA strands would become decidedly more advantageous than their breaking.
These sequences are believed to be the earliest, primitive forms of life. In an RNA world, natural selection would have targeted RNA sequences in competition with each other. Only the most efficient in terms of catalysis and self-reproduction would have survived to evolve and form the modern RNA.
The competition between RNAs may have favored the emergence of cooperation between different chains, thus paving the way for the first proto-cells. Within this RNA set, some may have developed the ability to catalyze the formation of a peptide bond with the evolutionarily advantageous consequence of being able to generate accessory peptides for the catalytic activities of ribozymes. In the same way, all the other chemical molecules that characterize it today, such as DNA, lipids or carbohydrates, could also have been recruited into the process of life formation.
Later developments
Patrick Forterre speculated that viruses may have been necessary tools for the RNA-to-DNA transition of Eubacteria, Archaea and Eukaryota. He proposed that the last common ancestor among the three domains may have been an RNA virus. Some viruses would later adopt the DNA, much less subject to external damage, starting to infect the organisms belonging to the three domains with this nucleic acid, thus also allowing their evolution.
Alternative theories
As mentioned in part, there is a different version of the hypothesis, called the pre-RNA world hypothesis. According to this theory, another nucleic acid existed before RNA. Among those proposed, there is above all PNA, more stable than RNA and easier to synthesize in prebiotic conditions (in which the formation of ribose and the addition of phosphate groups, both absent in PNA, is decidedly problematic). TNA and GNA have also been proposed as pre-RNA nucleic acids.
A further theory, partly complementary, is that of the hypothesis of the world a PAH (or PAH, polycyclic aromatic hydrocarbons).
World-related implications of RNA
The hypothesis of the RNA world, if true, has important consequences related to the definition of life itself. For most of the twentieth century, the scientific community regarded life as a combination of DNA and proteins, considered the two dominant macromolecules, relegating RNA to the status of a mere accessory molecule. This hypothesis instead places the RNA at the center of the origin of life. This is suggested by numerous studies which, in the last ten years, have re-evaluated the role of RNA, discovering previously unknown functions and highlighting its critical role in the functioning of life. In 2001 the three-dimensional structures of ribosomes were resolved, highlighting that the catalytic site is composed of RNA and not of peptides as previously hypothesized. Further discoveries in this sense have been related to the role of small nuclear ribonucleoproteins (snRNPs) in pre-mRNA processing and RNA editing, reverse transcription and telomere maintenance.
