The Genetic Revolution
"Genome decoding is part of routine medical examination"
Department of Science "Newspapers.Ru" tells about the history of genomics,
its development in the world and in Russia and how it will change the world in the futureNikolay Podorvanyuk, Vladimir Pokrovsky, "Gazeta.
In connection with the publication of an article in which this is stated, the science department of the Newspaper.Ru" decided to tell its readers about the history of genomics, genetic research that is being conducted in this direction in Russia, and how genomic technologies will change the world in the future.
Last Thursday, an article was published in the journal Nature (Fu et al., Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants), in which it was reported that Europeans on average have a greater number of potentially pathogenic genetic mutations than Africans. It was sensitive, but far from the most important news that researchers from the United States came to after examining the genomes of 6.5 thousand compatriots. The main news was that both of these races, which make up the "modern man" species, have been experiencing, in the literal sense of the word, a "genomic revolution" in the last five millennia. It was during this period that their genetic diversity began to grow dramatically – mutations, or, in scientific terms, gene variants (replacing one of the four letters of the gene alphabet with another) began to multiply at a staggering rate - for five thousand years, at the age of our species in a hundred or more millenniums, about 700 thousand of these accumulated in our DNA variants, and 81% of them among Euro-Americans and 58% among African-Americans arose during this relatively short period. Scientists explain the difference by the age of the races and their unusually high rate of reproduction.
This discovery, like many of those that have been made in recent years, amazes the imagination and, first of all, surprises people who are not involved in genomics: how can all this be learned from the composition, even if it is the main one for our life, but still just a molecule? What else can she give?
Hooligan discoveries One of the avalanches of scientific news in recent years has been created by genomic research, which received an explosive boost after Craig Venter completely sequenced human DNA.
Of course, to be fair, it should be said that this achievement did not affect the course of events too much – if there had been no Venter, the genome would have been read in the same way a few months later by a giant international consortium. It was Venter's personal war, in which he won by clicking on the nose of the international genetic community, which once did not give him grants; and the fact that it was he, and not the consortium, who became the catalyst for further events, gave the whole genomic epic a somewhat hooligan connotation.
Further events were not long in coming: discoveries poured in like a cornucopia: the genome of a dog (Venter's dog), the genome of a mouse, cat, pig, monkey, and so on throughout the list of animals and plants. The speed of sequencing began to grow rapidly, and sequencing itself began to become cheaper just as rapidly. In the period 2007-2010, it fell a hundred times – from a million dollars to ten thousand. Now the cost is approaching a thousand, and there has already been talk of thirty-dollar sequencing.
Using genome data, scientists began to understand the past of mankind, and at the very end of the twentieth century, paleogeneticist Svante Paabo declared that we have nothing in common with Neanderthals, and that they represented a separate humanity. However, he later found out that we still inherited a small number of genes from them, but then Paabo found a representative of another humanity from a fragment of a finger joint - a man from Denisova Cave. And today there are no guarantees that the number of extinct humanity will not continue to grow.
But the main wave of discoveries fell on medicine. Geneticists began to detect genes or their mutations responsible for a particular disease in DNA at a terrible speed. They started talking about the imminent, literally in a few decades, the arrival of a new medicine that will be able to eradicate many hereditary and still incurable diseases; the ancient dream of a universal panacea is about to be realized, the public thought.
Gerontologists revived, began to detect various genetic factors that cause aging. They even talked about the possibility of immortality.
At the same time, the structure of the genome itself is clarified. For a long time, scientists were very concerned about the fact that the vast majority of DNA does not contain any genes and does not affect anything at all – it was called "junk" DNA. This fall, it turned out that at least 80% of this genetic "garbage" is not even garbage at all, but a complex and still completely incomprehensible system that controls the work of genes.
Craig Venter, who "hooliganized" genomics of the XXI century, does not let himself be forgotten. A few years ago, he and the staff of the research institute, which was named after him, created a bacterial cell working on an artificially synthesized genome. Thus, he staked out a completely new topic – the topic of creating artificial organisms, a topic that is ethically very controversial, but theoretically feasible.
And more recently, Venter came up with another fantastic proposal – to search for microorganisms on Mars (he is sure of their existence), sequence them on the spot, send a digital copy of them by radio to Earth, and recreate them here using a 3D bioprinter.
In this sense, Venter plays the role of a kind of metronome, throwing momentum after momentum to the world, constantly reminding that genomics has many more possibilities that no one has even had time to think about yet.
"We know a lot now, and even know quite a lot, but we understand very little," he said about genomics to the newspaper.En" Professor of Moscow State University Mikhail Panteleev. Each gene can have many functions and work differently depending on how it is controlled by genetic "garbage", what kind of neighborhood it has, what company it works for, and so on. And until we figure it all out, and this may not happen very soon, surprises may be waiting for us at any moment, more often unpleasant than pleasant. Scientists are just accumulating information and are just beginning the difficult task of understanding it.
"A beautiful biological task"Fortunately, Russian scientists have a number of good results in this field of research.
Thus, Professor of Bioinformatics, Deputy Director for Science of the Institute of Information Transmission Problems of the Russian Academy of Sciences, Doctor of Biological Sciences Mikhail Gelfand noted the activities of Alexey Kondrashov, winner of the Megagrant, who created a laboratory of evolutionary genomics at the Faculty of Bioinformatics and Bioengineering at Moscow University.
"He bought a good sequencer for a megagrant. What I like about this group is that they are not making another human genome or a cancer genome," said Mikhail Gelfand, "they have very original biological tasks and the most intensively working sequencer in Russia.
They also do something for colleagues from other institutes, but if we talk directly about them, they have a very beautiful biology. For example, there are such fish – sticklebacks – which are freshwater and marine. In the 1970s, these sticklebacks were settled in lakes that formed on the site of GULAG quarries in the north of the country. Kondrashov's group went, caught sticklebacks and looked at the places where the genomes of marine and freshwater sticklebacks in these hybrids differ. They found two dozen places in the genome where freshwater variants were rigidly fixed. This is what seems to be really responsible for life in fresh water. Biologically, this is a very beautiful task."
Gelfand also mentioned the discovery of the Denisov man, which was mentioned above, and which became one of the biggest discoveries of recent years, not only in biology, but in all science. "We are terribly lucky that the Denisova cave is located in Altai," says Mikhail Gelfand. "There are only bones from Russia, but in fact, archaeologists have learned to work carefully with bones, so they are suitable for determining the genetic sequence. But this is the biggest discovery in recent years, actually the third branch of humanity: the Neanderthals, we and, finally, the Denisovans. There are a lot of different questions immediately arise, because they are closer to the Neanderthals in the nuclear genome, and further from us and from the Neanderthals in the mitochondrial genome, further than we and the Neanderthals are from each other. That is, on the maternal side, they come from completely incomprehensible from whom, from some erectus, apparently. There, in fact, the story is almost detective. Russia participates with bones, the sequence is determined in Germany, but it's incredibly interesting."
On the website of the population Immunogenetics group of the N. I. Vavilov Institute of General Genetics of the Russian Academy of Sciences (IOG RAS), some of the results obtained by this group are given, we quote them: "For the first time, a comparative genetic and demographic study of three megacities was conducted: Moscow, Minsk and Kharkiv… The accumulation of rare unique alleles for the main ethnic groups in the studied megacities was noted. For example, Belarusians in Minsk have only three unique rare alleles, Russians in Moscow and Ukrainians in Kharkiv have thirteen alleles each, which correlates well with the established lower migration level and the average migration radius in Minsk."
A large number of results are presented on the website of the Laboratory of Population Genetics of the Medical and Genetic Research Center of the Russian Academy of Medical Sciences. The laboratory staff participates in international projects on population genetics (in particular, in the project "Genography" – The Genographic project), which analyzes the characteristics of different ethnic groups and attempts to reconstruct history based on this.
One of the leading employees of this laboratory is Oleg Balanovsky, whose work was described by "Газета.Ru ".
A Laboratory of Algorithmic Biology was created on the basis of the St. Petersburg Academic University of the Russian Academy of Sciences under the leadership of another Megagrant laureate, Professor Pavel Pevsner. Its main task is to solve the most important algorithmic and computational problems of modern genomics and proteomics. The laboratory is developing new approaches to the sequencing and assembly of genomes, as well as to the identification and sequencing of proteins, antibodies and antibiotics. The laboratory's website says that its first frontier "will be one of the most important tasks of modern bioinformatics – the creation of a genome assembler (fragment assembler) that works better than existing assembly algorithms." "We want to develop an assembler that will be able to accurately collect not only the genomes of cultured bacteria, as now, but also any others – including uncultivated ones. This is critically important for the study of the microbiome (that is, a set of microbial genes that affect the environment, and in this case, the human body) of a person and the development of new antibiotics," the scientists write.
Genetic FacebookAs already mentioned, ten years ago the cost of decoding the human genome was millions of dollars, and now it is approaching a thousand.
Experts agree that in the near future, the decoding of the genome will become the same routine procedure as a blood test. "Indeed, it may well be part of a routine medical examination right now," says Mikhail Gelfand, "and amazing things happen there. In general, doctors do not know genetics well, and there are a lot of difficulties with interpretation. For example, you see a mutation, it's in an important gene, but even though you know that it's an important gene, you don't know if this mutation is harmful in itself or not. I have colleagues working in the USA, they have created a program that allows you to determine the potential harm from a protein mutation – whether a protein with such a mutation will work or not. Initially, it was a purely academic project. Now they are terribly nervous, because the level of responsibility has become completely different, because doctors are really starting to use it. A printout of mutations comes from the laboratory, and then they need to be interpreted somehow. And this, apparently, will develop quite quickly in different directions.
Another thing that is beginning to be done in medicine is the molecular diagnosis of cancer. First there was a classification by localization. Then I was on cytology, on cellular origin. And now molecular cancer diagnoses are gradually beginning, that is, it turns out what exactly broke down in the cells. It became clear that cancers are heterogeneous, and this affects both the diagnosis, the prognosis, and the choice of treatment. Then it turns out that if you have such a molecular diagnosis, then you can use a drug that, in principle, was made for a different type of cancer, for cancer of a different localization. Since the molecular breakdown is the same, and the drug is already approved for use, you can try to use it for treatment in other cases. That is, such a transfer of drugs based on the similarity of molecular targets. And this, apparently, may well turn out to be some kind of reasonable area. There are already examples of this kind."
Another direction of the future is the creation of a social network based on the decoding of the genome, with the help of which it is possible to establish the degree of kinship for any two people or to gather people with the same predispositions.
A similar project – 23andMe – was launched in 2007. The name of the company comes from the number of pairs of chromosomes in each healthy nucleus-containing human somatic cell. Anyone can send saliva samples to the company, and then get data about their genetic characteristics, in particular, about their propensities to diseases. He will be able to share this information with other project participants, doctors and relatives at will. Probably, in the coming years, it is the social network developed by 23andMe that will become a "genetic Facebook", since the company enjoys the support of Google (23andMe received $ 3.9 million from it, and one of the founders of Google, Sergey Brin, is married to the founder of 23andMe, Anna Wojcicki).
So far, 23andMe does not work with users from Russia. The reason for this is Russian legislation prohibiting citizens from sending any biological material for genetic analysis outside the country without special permission from the Ministry of Health of Russia (however, so far no one can forbid a person to take himself out of the country). "Of course, we have an interest in establishing our service here; and we will do it as soon as Russian laws allow it," 23andMe representatives say.
Portal "Eternal youth" http://vechnayamolodost.ru04.12.2012