Three, six, code
Galina Kostina, "Expert"
The two of them stood in silence on the blooming meadow. The aching smell of heated grass, flowers, the fluttering of butterflies, the slight buzzing of insects and the expanses lost in a blue-white haze were stronger than words. And yet he couldn't resist: "Imagine, all this splendor was born from a tiny protoviroid with DNA from three hundred nucleotides!" His wife poked him in the chest with her fists in annoyance.
"A person is uncomfortable on Earth without understanding how life appeared on it. But the funny thing is that he is comforted by any explanation, whether it is religious or materialistic. Religious is also good, but by definition it does not explain how God did it. Scientific theories try to suggest mechanisms, but they almost always run into many obstacles. I think that now two hypotheses look more or less plausible: the RNA world and mine," says Professor Anatoly Altstein, chief researcher at the Institute of Gene Biology of the Russian Academy of Sciences, who came up with the hypothesis of the origin of the first living organism, which he called a protoviroid. His hypothesis explains the appearance of the first gene and the genetic code.
A billion years without a traceIt is believed that our Earth is 4.6 billion years old.
Homo sapiens, which today is trying to solve the issues of its origin, diverged from the monkey only 5 million years ago, the mammals to which we belong appeared about 300 million years ago, and the first vertebrates – about 500-600 million years ago. The deeper researchers dive into the thickness of time, the more difficult it is for them to find traces of life. But they continue to dig, literally and figuratively, in the mountains of Australia, then in Africa, scraping rocks and studying invisible inclusions with the help of the most modern equipment. There they are looking for traces of the first prokaryotes – the simplest single-celled organisms that do not have a nucleus. The latest data obtained on the basis of studying the remnants of stable and radioactive carbon isotopes in the rocks of Greenland suggest that something alive that left these isotopes in the traces of its vital activity already existed 3.7 billion years ago. But if the traces of the first prokaryotes can be "felt", then one can only guess about the life of the first living beings, which lasted about a billion years.
Scientists consider the hypothesis of our compatriot Alexander Ivanovich Oparin to be the first scientific hypothesis of the origin of life. It was he who made an attempt to explain the appearance of the first organic compounds from inorganic ones. And although Oparin, most likely, was wrong, considering the first living organisms to be small isolated pieces of organic gel – coacervates, in which protein-like structures could form, he acted as a kind of catalyst for this scientific direction. Numerous experiments conducted later, including the famous experiments of Stanley Miller, showed that amino acids – building blocks for proteins - can arise in a test tube from a mixture of ammonia, methane, hydrogen and water vapor under the influence of a spark or ultraviolet light. In the course of numerous experiments carried out by various research groups, not only amino acids were obtained, but also nitrogenous bases, sugars, fatty acids, nucleotides (building blocks for DNA and RNA). It can be assumed that on the prebiotic Earth there was a metabolism without the participation of living organisms (abiotic metabolism), as a result of which thousands of organic substances were formed and disintegrated. There is reason to believe that among them there were several dozen of those that were needed for the emergence of life. Lipid vesicles (liposomes), similar to cells, but devoid of genes, could appear. And yet these were disparate parts of life, but not the intricately organized life itself.
Since the discovery of the structure and role of DNA in the cell, it has become clear that all previous reflections on the origin of life are not suitable for the role of hypotheses explaining the appearance of the first living beings, of which genes must be an obligatory part. It became clear that the main life process is the reproduction of genetic information – replication (DNA synthesis on matrix DNA). A special protein, the enzyme polymerase, helps this synthesis. And the realization of genetic information in the form of proteins occurs in two stages: RNA is synthesized on DNA, rewriting the necessary information from the gene (transcription), and then these RNAs serve as matrices for building proteins in special molecular machines – ribosomes (translation). Nature uses a triplet genetic code to transform the genetic information contained in DNA consisting of nucleotides into proteins consisting of amino acids. Each amino acid has its own triplet (three nucleotides) or two or three triplets. But this is a modern system, complicated at least by the fact that it involves two large worlds of macromolecules: polynucleotides (DNA and RNA) – information carriers and polypeptides (proteins) that perform almost all functions in the body due to their chemical reactivity. As Francis Crick, one of the discoverers of the DNA structure, once remarked, it would be much easier to approach the problem of the origin of life if there were only one family of macromolecules.
The same Cry, together with the American chemist Leslie Orgel, suggested that RNA appeared first. The hypothesis of the RNA world was later developed by the Nobel Prize winners Thomas Cech, Philip Sharp and Walter Gilbert. The hypothesis was and still remains tempting. In fact, RNA can be not only a carrier and translator, but also a carrier of information (as in some viruses). But to reproduce, she needs an enzyme that is too complex for it to be randomly assembled from amino acids. The triumph of the adherents of the RNA world was the discovery of RNAs with enzymatic activity – they were called ribozymes. The diversity of RNAs (i.e. informational, ribosomal, transport, various small RNAs) and their participation in many life processes is another argument in favor of this hypothesis. The structure of the transport RNA, which works in tandem with the ribosome when assembling proteins from amino acids according to the information provided by the informational, or matrix, RNA, suggests that it could be the first molecule that solves one of the most painful tasks – the formation of the genetic code: after all, it binds a triplet of nucleotides with the corresponding amino acid. But, according to Altstein, this hypothesis has its weaknesses.
In the modern world, RNA and DNA chains consist of so-called right nucleotides (in the prebiotic world, both right and left isomers should have existed, chains with the same isomers are called chirally pure). So, the probability that a single right and left nucleotides can form a chirally pure RNA chain containing at least 200, and preferably 300 nucleotides, is extremely low. A chain of multi-dimensional nucleotides can never be a matrix on which the following chains will be synthesized.
Altstein also has questions about the catalytic properties of ribozymes. The fact is that modern protein enzymes involved in replication and transcription are of the so–called process type: they sit on the matrix DNA and synthesize a complementary chain, deftly stringing nucleotides one by one onto the matrix. One molecule of such an enzyme is capable of copying a long matrix. An RNA enzyme is a different type of ribozyme, it pulls a pair of nucleotides to the matrix, hooks, then goes for the next ones. At this rate, he will never get a complementary chain: everything will fall apart while he is crawling like this. The alternative is a set of ribozymes that will simultaneously attach many nucleotides to the matrix at once.
And finally, as Altstein says, the royal question is: how did the formation of an integral genetic system, including the genetic code and protein synthesis, happen?
Vague assumptions that the code once formed by chance and was fixed may suit someone, but not Altstein, who has a very definite version, which he called the progen hypothesis. She postulates that the first genetic system was a single gene – a chain of single-stranded DNA and a protein enzyme that this gene encodes. The enzyme promotes the reproduction of the genetic system. The gene is assembled not from single nucleotides, as in the hypothesis of the RNA world, but from progenes - triplets of nucleotides with a tail in the form of a "non–random" amino acid. This progen, in fact, solves the problem of the genetic code – the correspondence of the three nucleotides to a certain amino acid. And the structure of the progen makes it possible to synthesize both a polynucleotide (DNA) and a polypeptide (enzyme) at the same time.
And progeny is betterIt all started with a love of viruses.
In his first year of medical school, Altstein made a report in which he claimed that viruses are living organisms. "Then there were heated debates on the topic of viruses, whether it was a substance or a creature," he says. – And then I supported the point of view of some scientists that viruses could be the first living organisms. Although there were much fewer arguments in favor of this hypothesis than there are now, I passionately defended this view." After the institute, Altstein became a virologist and dealt with smallpox, tick-borne encephalitis, adenoviruses, and most of all, malignant oncogenic viruses. He was inspired to think about the origin of life by the famous biologist or physicochemist, as he called himself, Lazar Mekler, who later came up with the hypothesis of the stereochemical code of proteins. In 1979, Mekler was assigned to be the editor of two issues of the journal of the Mendeleev Society devoted to the origin of life. Mekler wrote the title article, and Altstein and another well-known virologist Nikolai Kaverin commissioned an article on the origin of viruses. Two virologists shared the topic. Kaverin, as a great connoisseur of the modern history of viruses, wrote about his own, and Altstein had to delve into the hypothetical beginning of the beginning. At the time of receiving the assignment, of course, there was no hypothesis, there were only some intuitive assumptions. At that time, ideas about the origin of life as the origin of the genetic system were only being formed and there were disputes about which molecule was the first – DNA, RNA or protein, but many were already inclined to the idea of the primacy of RNA. By the way, at that time ribozymes had not even been discovered yet.
Altstein struggled with the traditional notion that polynucleotides are assembled from individual nucleotides, and polypeptides from amino acids. But then how does the connection between these sequences arise, which allows the gene to contain information about a particular sequence of a particular protein? Angry from his own brain powerlessness, Altstein went to bed, and in a dream floating nucleotides and amino acids appeared to him, and a pair of nucleotides plus an amino acid was connected to the same pair, then to the next, and so chains of nucleotides and amino acids were obtained simultaneously. He woke up. It was early morning. And Altstein attacked this idea of simultaneous synthesis of a polynucleotide and a polypeptide. It was on the idea, because the couples he dreamed of did not solve the issue of the genetic code. Why was it necessary to simultaneously synthesize a meaningless chain of nucleotides and a meaningless protein?
He thought that in the end, the best option would be a triple of nucleotides with an amino acid physicochemically close to these nucleotides. He sort of delved into those first organic compounds that could have arisen on the primordial Earth, and selected for this venture a pair of nucleotides and a nucleotide with an amino acid. "It was necessary to combine the two with the third nucleotide. Here an important role is played by the amino acid in this nucleotide, which interacts with the first two. Stereochemical analysis has shown that some pairs of nucleotides and certain amino acids interact with each other better than others. Therefore, I call the amino acid in this combination non–random, it "likes" these nucleotides, and it "likes" them," he explains why these compounds could successfully bind.
But so far, the connection in such a trio is weak. Two nucleotides are connected by a strong covalent bond, and with the third and the amino acid – by weak physico-chemical bonds. To strengthen this connection, we need another three – complementary. It will turn out to be a six, which will be supported by hydrogen bonds between complementary nucleotides. Such a construction will last longer than an unstable triple, and will give time and opportunity to bind the dinucleotide to the third nucleotide by covalent bond. Then the triples will disperse, and they will already be stable. Altstein later called these triples progenes. In his opinion, progenes solved many problems that remained questionable in the hypothesis of the RNA world. First, the selection of substances. In Altstein, it begins to act immediately: only the "right" substances (nucleotides and amino acids) can enter the complementary six, which will then be used for the emergence and reproduction of the first genetic system. In triples and then in the gene, not ribonucleotides (from which RNA is obtained) are selected, but deoxyribonucleotides (from which DNA is obtained), because chemically ribonucleotides would not be suitable for such a design. And no simultaneous synthesis of a gene and a protein would have worked. Secondly, the structure of the progen solves the problem of the genetic code – a triplet of nucleotides corresponds to a "non-random" amino acid.
And thirdly, when the progenes begin to assemble into a chain (see the diagram for more details), there will be simultaneous assembly of the polynucleotide - the future gene and the polypeptide – protein–enzyme. When the assembly is completed, this protein enzyme will be processive, unlike ribozyme. It will remain on the gene and will then participate in the synthesis of complementary chains and proteins at the same time. So the first genetic system will appear.
When Kaverin read the part of the article written by Altstein, he remarked: "Well, you give! We were just asked to think about the origin of the virus, and you're trying to solve the problem of the origin of life!" Mekler also liked the idea, and the article was printed.
Factory stampingAnatoly Davidovich had to abandon his hypothesis for several years, although some questions in it remained not fully "twisted".
Altstein's daughter began to study Hebrew. The KGB wanted to shake out of her "names, addresses and appearances." Altstein stood up, as a result of which he was fired from the Institute of Virology due to staff reductions. They said that oncoviruses, which he mainly dealt with, were no longer interesting. There were protests, going to the authorities, letters. The bureaucracy was idling. But Altstein now warmly recalls how many scientists stood up for him at the risk of themselves. The President of the Academy of Sciences Anatoly Alexandrov and his deputy Yuri Ovchinnikov managed to attach Altstein to the Institute of General Genetics. At first, he worked there on bird rights, then, when Ovchinnikov, as a member of the Central Committee, finally beat him off from the security guards, with a group that had transferred from the Institute of Virology.
He returned to the hypothesis in 1987, when academician Alexander Spirin, also fascinated by the problems of the origin of life, but adhering to the hypothesis of the RNA world, which had already become the main one at that time, invited him to a seminar at his institute in Pushchino. After the report, specialists in stereochemical analysis suggested Altstein to check on models whether his speculative constructions could exist in nature. Like, it's good to write letters on the board, and you try to lay out three-dimensional structures. Valery Lim, the head of the laboratory, helped him in this. To begin with, he twirled the models himself and said: I thought to debunk them right away, but no, maybe it will work, let's post it yourself, and then we'll see together. "I folded, twisted, turned: there are many combinations of these models, but something didn't stick well," Altstein says. – Excited, I went home, and you will laugh – I had a dream again: first a round red oxygen atom floated out – like in a plastic model, and then an amino acid floated up to it. I barely waited for the morning, sat under the gate until the institute and laboratory were opened, and rushed to the models – everything worked out. Lim came, looked and answered: Well, that's better, go on."
Altstein honed his hypothesis by constantly consulting with chemists. As a result, he formulated the idea of progenes, from which the first genetic system is obtained – a gene and an enzyme, it is also the first living organism, named by Altstein protoviroid by analogy with a virus. "Because the protoviroid at first did not have its own home and, just like the virus, led an intermittent lifestyle," he explains. It is assumed that the protoviroid arises in the vesicle-liposome, because it is there that, with a significant concentration of substances, triples of nucleotides connected to a "non–random" amino acid (progenes) can form, and from them a gene with an enzyme. At this stage, the liposome is not part of the first living organism, but only a condition of its existence. It quickly collapses, and the protoviroid is forced to look for a new hotel room – a new liposome at the moment of its occurrence.
Once appearing, the protoviroid will reproduce itself using progenes as "food". More and more protoviroids will appear in the liposome. However, the reproduction of one gene and one enzyme, even if they are called the first living organism, still seems to be an unpromising process, since the simplest modern organisms contain at least 250 genes. "But development doesn't stop there," Altstein explains. "The system will evolve according to Darwin, a protocell will arise." But the further evolution of Altstein is no longer exciting. The main thing is to launch a system of minimal self–reproducing genome – protoviroid. It was that brilliant event of nature, after which further evolutionary steps are almost factory stamping.
Portal "Eternal youth" www.vechnayamolodost.ru11.02.2008