03 December 2012, 16:12 Science Text size A A A

“Genome decoding is part of a routine medical examination”

The science department of Gazeta.Ru talks about the history of genomics, its development in the world and in Russia, and how it will change the world in the future

Nikolay Podorvanyuk , Vladimir Pokrovsky close 100%

Europeans, on average, have a higher number of potentially disease-causing genetic mutations than Africans. In connection with the publication of an article in which this is stated, the science department of Gazeta.Ru decided to tell its readers about the history of genomics, genetic research being carried out in this direction in Russia, and how genomic technologies will change the world in the future.

Last Thursday, a paper published in the journal Nature reported that Europeans, on average, have more potentially disease-causing genetic mutations than Africans. This 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 species “modern man,” have been experiencing, in the literal sense of the word, a “genomic” revolution over the past five millennia. It was during this period that their genetic diversity began to grow dramatically - mutations, or scientifically, gene variants (replacement of one of the four letters of the genetic alphabet with another) began to multiply at a stunning speed - in five thousand years, when the age of our species is a hundred or more millennia Our DNA has accumulated about 700 thousand such variants, and 81% of them in Euro-Americans and 58% in African-Americans arose in this relatively short period. Scientists explain the difference by the age of the races and their unusually high reproduction rate.

This discovery, like many of those that have been made in recent years, amazes the imagination and, first of all, surprises people not involved in genomics: how can all this be learned from the composition of molecules, albeit the main one for our life, but still just molecules? What more can she give?

Hooligan discoveries

One of the avalanches of scientific news in recent years has been 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 greatly influence the course of events - if Venter had not been there, 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, which he won by punching the international genetics community that had once denied him grants; and the fact that it was he, and not the consortium, who became the catalyst for further events, gave the entire genomic epic a somewhat hooligan tone.<2>

Further events were not long in coming: discoveries rained down like from a cornucopia:

the genome of a dog (Venter's dog), the genome of a mouse, cat, pig, monkey, and so on throughout the entire 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 is already talk of thirty-dollar sequencing.

Using genome data, scientists began to understand humanity's past, and at the very end of the twentieth century, paleogeneticist Svante Pääbo declared that we have nothing in common with Neanderthals, and that they represented a separate humanity. True, he later found out that we did inherit a small number of genes from them, but then Paabo, using a fragment of a finger joint, found a representative of another humanity - the 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 came in medicine. With alarming speed, geneticists began to discover genes or mutations in DNA that are responsible for a particular disease. They started talking about the imminent arrival, literally in a few decades, of new medicine that will be able to eradicate many hereditary and still incurable diseases; The audience thought that the ancient dream of a universal panacea was about to come true.

Gerontologists perked up and began to discover various genetic factors that cause aging. They even started talking about the possibility of immortality.

At the same time, the structure of the genome itself is being clarified. For a long time, scientists were very concerned about the fact that the overwhelming majority of DNA does not contain any genes and generally does not affect anything - 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.<3>

Craig Venter, who “bullied” genomics of the 21st century, also does not let himself be forgotten. Several years ago, he and the staff of the research institute that was named after him created a bacterial cell that runs 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 realizable.

And just recently, Venter came up with another fantastic proposal - to look 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 impulse after impulse to the world, constantly reminding us that genomics still has many possibilities that no one has even thought about yet.

“We now know a lot, and even can do quite a lot, but we understand very little,” MSU professor Mikhail Panteleev said about genomics to Gazeta.Ru. Each gene can have many functions and work differently depending on how it is controlled by genetic "junk", what kind of neighborhood it is, what company it works for, and so on. And until we figure it all out, and this may not happen soon, surprises can await us at any moment, more often unpleasant than pleasant. Scientists are still only accumulating information and are just beginning the difficult task of understanding it.

"Beautiful biological problem"

Fortunately, Russian scientists have a number of good results in this area of research. Thus, professor of bioinformatics, deputy director for science of the Institute for Information Transmission Problems of the Russian Academy of Sciences , Doctor of Biological Sciences Mikhail Gelfand noted the activities of Alexey Kondrashov , a “megagrant” laureate who created a laboratory of evolutionary genomics at the Faculty of Bioinformatics and Bioengineering at Moscow University.

“With the megagrant, he bought a good sequencer. What I like about this group is that they are not making just 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 do something for colleagues from other institutes, but, speaking directly about them, they have very beautiful biology.

For example, there are fish - sticklebacks - which can be freshwater or marine. In the 1970s, these sticklebacks were introduced into 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 differ between these hybrids. They found two dozen places in the genome where freshwater variants were firmly fixed.

This is what appears to be truly responsible for life in fresh water. Biologically, this is a very beautiful problem.”

Gelfand also mentioned the discovery of Denisovan man, which was mentioned above, and which became one of the largest discoveries in recent years not only in biology, but in all of science. “We are extremely lucky that Denisova Cave is located in Altai ,” says Mikhail Gelfand. “There are only bones here from Russia, but in fact, well done archaeologists for learning to work carefully with bones, so that they are suitable for determining the genetic sequence.” But this is the largest discovery in recent years, in fact, the third branch of humanity: Neanderthals, us and, finally, Denisovans. A lot of different questions immediately arise there, because in terms of the nuclear genome they are closer to Neanderthals, and in terms of the mitochondrial genome they are further from both us and from Neanderthals, further than we and Neanderthals are from each other. That is, on the maternal side they come from a completely unknown source, 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 Institute of General Genetics named after N. I. Vavilov RAS (IOG RAS) some results obtained by this group are presented, we will quote them: “For the first time, a comparative genetic and demographic study of three megacities was carried out: Moscow , Minsk and Kharkov ... An accumulation of rare unique alleles for the main ethnic groups in the studied metropolitan areas. So, for example, only three unique rare alleles were identified among Belarusians in Minsk, while Russians in Moscow and Ukrainians in Kharkov had thirteen alleles each, which correlates well with the established lower level of migration and the average radius of migration in Minsk.”

A large number of results are presented on the website of the Laboratory of Population Genetics of the Medical Genetic Research Center of the Russian Academy of Medical Sciences.

Laboratory employees participate in international projects on population genetics (in particular, in the “Genographic” project ), in which the characteristics of different ethnic groups are analyzed and an attempt is made to reconstruct history based on this.

One of the leading employees of this laboratory is Oleg Balanovsky , whose work was described by Gazeta.Ru .

On the basis of the St. Petersburg Academic University of the Russian Academy of Sciences, under the leadership of another “megagrant” laureate, Professor Pavel Pevzner, the Laboratory of Algorithmic Biology was created. Its main task is to solve the most important algorithmic and computational problems of modern genomics and proteomics. The laboratory develops new approaches to sequencing and assembling genomes, as well as identifying and sequencing proteins, antibodies and antibiotics. The lab's website says its first frontier "will be one of the most important challenges in modern bioinformatics—creating a genome fragment assembler that performs better than existing assembly algorithms." “We want to develop an assembler that can accurately assemble not only the genomes of cultivated bacteria, as now, but also any other ones, including uncultivated ones. This is critically important for the study of the human microbiome (that is, the set of microbial genes that influence the environment, and in this case, the human body) and the development of new antibiotics,” the scientists write.

Genetic Facebook (the owner of the Meta company is recognized as extremist in Russia and is banned)

As already mentioned, ten years ago the cost of deciphering the human genome was millions of dollars, and now it is approaching a thousand. Experts agree that in the near future, deciphering the genome will become as commonplace as a blood test. “Indeed, this may well already be part of a routine medical examination,” 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 is in an important gene, but although you know that it is an important gene, you do not know whether this mutation itself is harmful 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 be functional 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 this.

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 starting to be done in medicine is molecular diagnostics of cancer.

First there was a classification by localization. Then there was cytology, cellular origin. And now molecular cancer diagnoses are gradually beginning, that is, it is becoming clear what exactly is broken in the cells. It became clear that cancers are heterogeneous, and this affects the diagnosis, prognosis, and choice of treatment.

Then it turns out that if you have such a molecular diagnosis, then you can use a medicine that, in principle, was made for a different type of cancer, for a cancer of a different location.

Since the molecular breakdown is the same and the drug is already approved for use, you can try to treat it in other cases. That is, such drug transfer is 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 future direction is the creation of a social network based on genome decoding, with the help of which you can establish the degree of relationship for any two people or gather people with the same predispositions.

A similar project, 23andMe , started in 2007. The name of the company comes from the number of pairs of chromosomes in each healthy nucleated human somatic cell. Anyone can send saliva samples to the company, and then receive data about their genetic characteristics, in particular, their propensities for disease. 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 is supported by 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).

For now, 23andMe does not work with users from Russia. The reason for this is Russian legislation, which prohibits citizens from sending any biological material for genetic analysis outside the country without special permission from the Russian Ministry of Health (however, so far no one can prohibit a person from taking himself outside the country). “Of course, we have an interest in establishing our service here; and we will do this as soon as Russian laws allow it,” say representatives of the 23andMe company.