On the origin of life and RNA. How scientists are looking for confirmation of the RNA-world theory. Life began with RNA The origin of life Modern RNA theories of the world

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RNA World - the hypothetical stage of living on Earth, when both the function of storing genetic information and the catalysis of chemical reactions was performed by ensembles of ribonucleic acid molecules. Subsequently, modern DNA -RNK-Clean life arose from their associations, a separated membrane from the external environment. The idea of \u200b\u200bthe world RNA was first expressed by Karl Vysoz in 1968, later developed Leslie Ordhell \u200b\u200band finally formulated by Walter Hilbert in 1986.

In living organisms, almost all processes occur mainly due to protein nature enzymes. Proteins, however, cannot be organized and synthesized in the cell de Novo. Based on the information laid in DNA. But the doubling of DNA is only due to the participation of proteins and RNA. A closed circle is formed, due to which, within the framework of the theory of self-religion of life, it was necessary to recognize the need for not only the abiogenous synthesis of both classes of molecules, but also a spontaneous occurrence of a complex system of their relationship.

Thus, RNA could be completely autonomously, catalyzing "metabolic" reactions, for example, the synthesis of new ribonucleotides and self-reproducing, keeping from the "generation" to the "generation" catalytic properties. The accumulation of random mutations led to the appearance of RNA catalyzing the synthesis of certain proteins, which are a more efficient catalyst, and therefore these mutations were fixed during natural selection. On the other hand, specialized storage facilities of genetic information - DNA have arisen. RNA has been preserved between them as an intermediary.

Footprints of the world RNA remained in modern living cells, and RNA participates in critical cell life processes:

In 2017, the possibility of uridine self-assembly from ribose, uracil and phosphoric acid was shown.

The ability of RNA molecules to evolution was clearly demonstrated in a number of experiments. Even before the opening of the catalytic RNA activity, such experiments conducted Leslie Orders with colleagues in California. They were added to the tube with RNA poison - the ethidium bromide, inhibiting RNA synthesis. At first, the synthesis paced was slowed down by poison, but about after nine "probidity generations" of evolution in the process of natural selection was brought a new RNA breed, resistant to poison. By consistent doubling doses of poison, the RNA breed was removed, resistant to very high concentrations. In total, 100 pierced generations were changed in the experiment (and much more generations of RNA, since generations were replaced inside each test tube). Although in this experiment, RNA replicate was added to the solution by the experimenters themselves, the Ordel found that RNA is capable of both spontaneous self-copying, without adding an enzyme, though much slower.

An additional experiment was later held in the laboratory of the German School of Manfred Eygen. He discovered the spontaneous self-rooting RNA molecule in a test tube with a substrate and RNA replicasa. It was created gradually increasing evolution.

After opening the catalytic activity of RNA (Ribosims), their evolution in an automated device under the control of a computer was observed in the experiments of Brian Pegel and Gerald Joyce from the Scripps Research Institute in California in 2008. The factor playing the role of the selection pressure was the limitations of the substrate, where the oligonucleotides were included, which Ribosim recognize and attached to himself, and nucleotides for RNA and DNA synthesis. When constructing copies, there were sometimes defects - mutations - affecting their catalytic activity (to accelerate the process several times the mixture was mutated with a polymerase chain reaction using the "inaccurate" polymeraz). On this basis, the selection of molecules took place: the fastest copying molecules quickly began to dominate in the medium. Then 90% of the mixture was removed, and a fresh mixture was added instead with substrate and enzymes, and the cycle was repeated again. For 3 days, the catalytic activity of molecules due to only 11 mutations increased 90 times.

These experiments prove that the first RNA molecules did not need to have sufficiently good catalytic properties. They developed later during evolution under the action of natural selection.

In 2009, Canadian biochemists from Montreal University of K. Bokov and S. Steinberg, having studied the main component of the ribosome of Escherichia coli bacterium, 23S-RRNA molecule, showed how from relatively small and simple ribosims could develop a protein synthesis mechanism. The molecule was divided into 60 relative to independent structural blocks, the main of which is the catalytic center (peptidyl-transferase center, PTC, PEPTIDYL-TRANSFERASE CENTR) responsible for transpaptidation (peptide communication formation). It was shown that all these blocks can be sequentially disconnected from the molecule without the destruction of its remaining part until the transpeptidation center remains. At the same time, it retains the ability to catalyze transpeptidation. If each connection between the molecule blocks is to present in the form of an arrow directed from that block, which is not destroyed during the separation, to the unit that is destroyed, then such arrows do not form a single closed ring. If the direction of the relationship was random, the probability of this would be less than one billion. Consequently, such a nature of links reflects the sequence of gradual addition of blocks in the process of the evolution of the molecule, which researchers managed to reconstruct in detail. Thus, the origins of life could stand relatively simple ribosim - the PTC center of the 23S-RRNA molecule, to which new blocks were then added, improving the protein synthesis process. The PTC itself consists of two symmetrical blades, each of which holds the CCA "-Helos one molecule TRNA. It is assumed that such a structure arose as a result of duplication (doubling) of one source blade. The method of artificial evolution was obtained functional RNA (ribosis) capable of catalyze transpeptide . The structure of these artificially derived Ribosims is very close to the structure of the protoribosomes, which the authors have "calculated".

About how self-reproduced RNA system looked like, there are different assumptions. Most often there is a need for aggregating RNA membranes or placing RNA on the surface of minerals and in the pore space of loose rocks. In the 1990s, A. B. Chetverin with employees was shown the ability of RNA to form molecular colonies on gels and solid substrates when creating conditions for replication. There was a free exchange of molecules, which when a collision could exchange areas, which shown experimentally. The whole set of colonies in connection with this quickly evolved.

After the occurrence of protein synthesis of a colony, able to create enzymes, developed more successfully. An even more successful colonies, formed a more reliable mechanism for storing information in DNA and, finally, separated from the external world of a lipid membrane, preventing the scattering of their molecules.

Pre-biotic models in which nucleotides are created are incompatible with the conditions necessary to create sugars (due to the large concentration of formaldehyde). So they should be synthesized in different places, and then transferred to some one place. However, they do not react in water. Anhydrous reaction easily bind purines with sugars, but only 8% of them connect the correct carbon atom on sugar with the correct nitrogen atom based on. Pyrimidines, however, will not react with ribosa, even in anhydrous conditions.

In addition, phosphates in nature necessary for the synthesis are extremely rare, as they are easily falling into the sediment. With the introduction of phosphate, the latter must quickly connect with the correct hydroxyl nucleotide group.

To nucleotides can form RNA, they themselves must be activated. Activated purin nucleotides form small chains on an existing template of pyrimidine RNA, but this process does not go on the contrary because pyrimidine nucleotides are not polymerized so easily.

Another hypothesis of abiogenic RNA synthesis, designed to solve the problem of low estimated probability of RNA synthesis, is the hypothesis of the world of polyaromatic hydrocarbons proposed in 2004 and implying synthesis of RNA molecules based on a stack of polyariamatic rings.

In fact, both hypothesis "pre-RNA of worlds" do not reject the hypothesis of the world of RNA, and modify it by posting the initial synthesis of replicating Macromolecules of RNA in primary metabolic compartments, either on the surface of associates, pushing the "world of RNA" to the second stage

Candidate of Biological Sciences S. Grigorovich.

At the earliest dawn of its history, when a person acquired a mind, and with him and the ability to abstract thinking, he became a prisoner of an insurmountable need to explain everything. Why the sun and the moon shine? Why do rivers flow? How is the world? Of course, one of the most important questions about the essence of the living. The sharp difference between the living, growing, from the dead, still, was too strung in the eyes so that it could be ignored.

The first virus described by D. Ivanovo in 1892 is a tobacco mosaic virus. Thanks to this discovery, it became clear that there are lively creatures more primitive than the cell.

Russian Microbiologist D. I. Ivanovsky (1864-1920), founder of virology.

In 1924, A. I. Oparin (1894-1980) suggested that in the atmosphere of a young land, consisting of hydrogen, methane, ammonia, carbon dioxide and water vapor, amino acids could be synthesized, which then spontaneously connected to proteins.

The American biologist Oswald Everver convincingly demonstrated in experiments with bacteria, which is precisely nucleic acids responsible for the transfer of hereditary properties.

Comparative RNA and DNA structure.

Two-dimensional spatial structure of the ribosis of the simplest Tetrahymena body.

Conceptual image of ribosome - molecular machine for protein synthesis.

The scheme of the process of "Evolution in the tube" (Select method).

Louis Pasteur (1822-1895) was first discovered that the crystals of the same substance - winic acid - can have two mirror-symmetric spatial configurations.

In the early 1950s, Miller from the University of Chicago (USA) had done the first experiment that simulates chemical reactions that could flow in a young land.

Chiral molecules, such as amino acids, mirrored symmetrical as the left and right hand. The term "chirality" itself comes from the Greek word "Hiros" - hand.

Theory of RNA World.

Science and life // illustration

At each stage of history, people offered their decision to riddling the appearance of life on our planet. Ancient who did not know the words "science" was found for an unknown simple and affordable explanation: "Everything that is around was once created by someone." So the gods appeared.

Since the origin of ancient civilizations in Egypt, China, then in the cradle of modern science - Greece, up to mid-centuries, the main method of knowledge of the world served observations and opinions of "authorities". Permanent observations unequivocally testified that living under the observance of certain conditions appears from the non-living: mosquitoes and crocodiles - from swamp tina, flies - from rotting food, and mice from dirty linen, shipped by wheat. It is important only to observe a certain temperature and humidity.

The European "scientists" of the Middle Ages, relying on the religious dogma on the creation of the world and the incomprehensibility of divine designs, was considered possible to argue about the birth of life only within the Bible and religious scriptures. The essence of created by God is impossible to comprehend, but you can only "clarify", using information from the sacred texts or under the influence of divine inspiration. Checking the hypothesis at the time was considered a bad tone, and any attempt to question the opinion of the Holy Church was considered as an unborn, heresy and sacrence.

Cognition of life trampled in place. The peak of scientific thought for two thousand years remained the achievements of philosophers of ancient Greece. The most significant of them were Platon (428/427 - 347. BC) and his student Aristotle (384 - 322 BC. E.). Plato, among other things, proposed an idea of \u200b\u200ban animation initially inanimate matter thanks to the establishment of an immortal intangible soul into it - "Psyche". So there was a theory of self-relocation of a living non-living.

Great for science The word "experiment" came with the era of the Renaissance. Two thousand years have needed for a person to decide to doubt the indispensability of the authoritative statements of the scientists of antiquity. One of the first brave friends known to us was the Italian doctor Francisco Radi (1626 - 1698). He spent an extremely simple, but spectacular experience: placing in several vessels in a piece of meat, one of them covered with a dense cloth, others - marley, and the third left open. The fact that fly larvae developed only in open vessels (which mugs could sit), but not in the closed (to which air access was still), abruptly contradicted beliefs of supporters of Plato and Aristotle about the incomprehensible life strength, wearing in the air and converting Non-living matter live.

This experimental experiments laid the beginning of the period of fierce battles between the two groups of scientists: the Vitalists and Mechanics. The essence of the dispute was on the question: "Can the functioning (and the appearance) of the lively be explained by physical laws, applicable also to inanimate matter?" The Vitalists responded to him negatively. "Cage - only from the cell, all alive - only from the live!" This provision put forward in the middle of the XIX century has become a banner of vitalism. The very paradox in this dispute is that even today, knowing about the "inanimate" nature of the components of our body of atoms and molecules and in general agreeing with a mechanistic point of view, scientists do not have experimental confirmation of the possibility of the origin of cell life from inanimate matter. No one has yet been able to "make up" even the most primitive cell from the "inorganic" present outside of living organisms, "parts". So, the final point in this epochal dispute is still to be delivered.

So how could life arise on earth? Sharing the positions of mechanics, it is easier to certainly imagine that life first had to arise in some very simple, primitively arranged form. But, despite the simplicity of the structure, it still should be life, that is, what has a minimal set of properties that distinguish live from non-living.

What are these critical properties? What, actually, distinguishes living from non-living?

Until the end of the XIX century, scientists were convinced that all living things were built from cells, and this is the most obvious distinction of it from inanimate matter. Thus thought before the discovery of viruses, which, although less than all known cells, can actively infect other organisms, multiply in them and produce offspring, which has the same (or very similar) biological properties. The first of the detected viruses, the tobacco mosaic virus, is described by the Russian scientist Dmitry Ivanovsky (1864-1920) in 1892. Since then, it has become clear that more primitive creations than cells can also claim the right to be called life.

The discovery of viruses, and then even more primitive forms of living - viroids, as a result, formulate a minimum set of properties that are necessary and sufficient so that the object under study can be called alive. First, it must be capable of reproducing like this. This, however, is not the only condition. If the hypothetical primary substance of life (for example, a primitive cell or molecule) was capable only to simply produce their exact copies, it would eventually be able to survive in changing environmental conditions on the young land and the formation of other, more complex forms (evolution) would be impossible. Consequently, our alleged primitive "limit of originality" can be defined as something, the most simply as possible, but at the same time can change and transmit its properties to descendants.

In recent years, more and more supporters find this theory of the emergence of life, becoming dominant in solving this issue. Its essence is that the founders of life were not proteins, but RNA molecules. The formation of components of monomer links of RNA - carbohydrate cycles of ribose and heterocyclic bases - as already shown, did not prevent fundamental difficulties. It is much more difficult to imagine the process of formation of directly nucleoside, and then the connection of the latter in the NC. Indeed, under the conditions of the homofamine process in a gas or liquid medium, such synthesis could be extremely difficult. However, it is relatively easily carried out under conditions of heterophase catalysis on a solid substrate. Many minerals of the earth's crust are acting as the latter: calcium carbonate, kaolinitis, montmorillonite, aluminum compounds, zeolites. At the same time, they contribute not only to accelerate the synthesis, but also the correct orientation of the reacting components. In such substrates, a crosslink was carried out first nucleoside, and then the formation of an inter -ucleotide bond with the participation of phosphoric acid or its derivatives. For example, it was possible to carry out the synthesis of oligisitidine, i.e. the short RNA molecule consisting of only one type of nucleoside, on a montmorillonite substrate from 5 "-phosphorimidazolidated citidin. Similarly, more complex oligonucleotides were obtained, containing nucleosides of different types. It is interesting that RNA The chain was stable a stable long time. At the same time, long oligonucleotides, being on a mineral matrix, could bind to the formation of hydrogen bonds between complementary bases. Between these di- and trinucleotides, interneucleotide communications could also be formed. So the synthesis of subsidiary RNA was carried out on RNA matrix, i.e. an analogue of transcription. A similar sequence of operations could also occur in the case of a matrix-directional synthesis of peptides on RNA: individual di- and trinucleotides were associated with AK molecules, for example, due to hydrophobic interactions or hydrogen bonds and transferred them to the RNA matrix. With a RNA molecule di- and trine Cleotydis interacted by hydrogen bonds. As a result, near the RNA circuit build nucleotides carrying AK. If they were located closely from each other, it became possible to form peptide bonds between the AK molecules with the formation of a polypeptide - a small "protein". Thus, the broadcast response was implemented, and without the participation of proteins-enzymes. It is especially important to emphasize that all these processes were carried out highly specific, since the formation of hydrogen bonds between different molecules is rather selective: the most stable those interaction in which the largest number of hydrogen bonds is being implemented. In conditions of equilibrium of processes, such selectivity led to reproduction of certain molecules: each matrix "produced" products inherent only to it. Such synthesis could be held in primary kapackers. This led to the accumulation of a clearly defined set of biomolecules in each of them, however, the diversity of the drops themselves and the conditions in which they existed, gave great opportunities for the selection of the most stable droplets, which was already a proto deevolution. Self-reproduced division of drops all increased in size and constantly became more complicated, involving new and new substances. So the first cell could arise.

There is, however, an ambiguity, whether RNA was the first life-forming molecule or existed more ancient predecessors. For some time ago, the synthesis of a chimera substance, called peptideucleic acid (PNA), in which the skeleton of the chains was formed by amino acid molecules, N- (2-aminoethyl) glycine, and heterocyclic bases were attached to this skeleton. Thus, the sucrosephosphate cable was replaced with a polypeptide. Currently, some researchers consider the PNA as a candidate for the role of a possible predecessor of RNA, although the prebiotic role of the PNK is still strictly proven.

Among the modern concepts of the birth of life, one of the dominant provisions occupies the theory of RNA-world. Let's try to figure out what it is.

The discoveries in the molecular biology of the last century led humanity to understanding the life of life at the chemical level. It turned out that the basis of the vital activity of any organism is two groups of substances-biopolymers: proteins and nucleic acids.

Proteins whose long, intensely rolled chains consist of dozens and hundreds of consistently associated amino acids, perform the role of working instruments and universal building material in the cell. Proteins-enzymes accelerate and direct all chemical reactions occurring in the cell, forming its appearance.

But proteins are temporary tools, the need for which is constantly changing through the life of the body. To store the same information about proteins, and therefore, the structure of the organism itself uses nucleic acids - DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). These long molecules, built of four types of nucleotides lurked from each other, are very similar in structure, but have different properties. Two DNA circuits directed in different directions form a rigid and stable double spiral in millions of pairs of nucleotides. RNA forms relatively short chains subject to a variety of chemical reactions and braided by loop themselves.

The structure of the DNA molecule. Image: Richard Wheeler / Wikimedia

Such a different structure explained by scientists fundamentally different functions of DNA and RNA. DNA turned out to be reliable, long-term storage of information about the proteins of the body, and RNA is a mobile, short-lived carrier of information. It is synthesized by proteins-polymerases on a DNA matrix and is responsible for deciphering information recorded in DNA, as well as for assembling proteins on DNA drawing.

All of this knowledge of the knowledge was accumulated by scientists by the mid-60s of the last century, becoming the forerunner of the present biotechnological revolution. But at the same time he put scientists who suffer over the problem of the birth of life, before the paradox.

For the existence of the first "alive", that is, biochemical systems capable of breeding and self-sustaining, sufficient DNA, RNA and protein. With the role of RNA, everything seems to be understandable - a typical molecule on blisters, which can not really know how and does not solve, but it is necessary to transfer information from DNA and the work mechanisms for the protein assembly. But proteins and DNAs clearly had to occupy a central place in the painting of the prehistoric world.

Information about the structure of protein-catalysts that can be able to persist, only being recorded in the DNA structure. At the same time, stable DNA, perfectly maintaining information, is not capable of independent chemical transformations, except, except, slow decay. What appeared in evolution earlier - skillful, short-lived proteins or reliable, but helpless DNA? One thing can not appear without the other, and the random one-time nucleation of a complex DNA RNA-protein self-reproducing system seemed incredible.

Here the views of scientists and appealed to RNA. RNA is not stable and terribly keeps information, but still keeps it. And what if we assume that the RNA circuit woven in the venice loops can work like the enzyme proteins, catalyzing, that is, accelerating, biochemical reactions? Let them cope with this task hundreds of times worse than proteins, but hypothetically such RNA catalysts could sustainably exist and multiply on the surface of the ancient land before the appearance of proteins and DNA. And their chemical instability would be even a plus, leading to a frantic pace of the evolution of primitive RNA fauna.

The structure of the precursor molecule of the matrix RNA. Image: Vossman / Wikimedia

The bold hypothesis turned out to be a prophetic, first ribosis were found in the early 80s - RNA-based biocatalysts. A little later, scientists received aptamers - RNA molecules capable of selectively binding certain substances. It turned out that RNA can perform work both by biocatalysis and molecular recognition. Yes, it turns out worse than the proteins, but still it turns out.

Since then, scientists leave no persistent attempts to obtain ribosim in the laboratory capable of stable copying (replication) of RNA molecules of any structure. Appearing at the dawn of evolution, similar to Ribosim would become a real "core" of the hypothetical RNA world, and its receipt would be tangible confirmation of the still speculative hypothesis.

Over the years of research, ribosis ligases were obtained, capable of sewing RNA molecules among themselves, and even polymerase ribosisms that copy small, homogeneous RNA fragments in their nucleotide composition. But on all complex, capable of biocatalysis and molecular recognition of sequences, they stubbornly bucks, refusing to work.

And recently in the authoritative magazine PNAS. An article was published on obtaining the first ribosym, a confidently copying RNA matrix of any nucleotide composition. During the experiments, scientists were replaced by evolution: by artificial selection in a test tube, they managed to create ribosim coping RNA with an inaccessible accuracy.

Each of the 24 rounds of the selection mutation began with copying the already existing enzyme in the biochemical process, called the Riboptz. This reaction is an analogue of a well-known polymerase chain reaction (PCR), which allows in a few hours to synthesize millions of copies of the desired DNA fragment. In order for the system to appear for artificial selection, the reaction was modified towards reducing copy accuracy. The frequency of errors reached 10% in terms of a separate nucleotide. Thanks to this scheduled random mutagenesis, scientists managed to get 10 14 (100 trillion!) Of various options for the original ribrosima. After completion of the reaction, mutant ribosis was picky by scientists: in the next round, the mutation passed only the fastest and accurate ribosis, capable of the best copying of the matrix.

After completing this painstaking work, the researchers received ribosim, called 24-3 polymerase. For the first time, the scientists hit Ribosim, capable of replicating small RNA chains of any sequence. With it, several aptamers managed to replicate. Then the tireless polymerase was copied catalytically active ribosim-ligase. But this achievement was the fact that with the help of 24-3 polymerases managed to replicate one of the transport RNA. These large, slyly braided in the figure like a clover sheet of the RNA molecule transfer the amino acid links to the place of assembly of protein chains and are an essential component of the protein synthesis apparatus.

The speed of operation of the obtained ribosym was extremely small, and the performance is incomparable with natural polymerase proteins, but the main thing is that it has been received, and it works. Now, to prove the possibility of the existence of an ancient RNA-world, scientists remained the last step - to create Ribosim, capable of steadily replicating itself. Having done it, humanity will receive a colony of self-copying RNA molecules in a test tube - a potential analogue of the first form of life on our planet.

For several months of work allowed researchers to approach the creation of an artificial prototype of primitive life. What could happen from natural selection for hundreds of millions of years? We have never been so close to the answer to this question.