To the last leaf

Genogeographers recreate the genealogical tree of peoples

Yuri Drize, newspaper "Search" No. 29-2016
Illustrations provided by O. Balanovsky

The large map "Peoples of Russia and Neighboring Countries" in a prominent place in the office of the head of the Laboratory of Genomic Geography of the Vavilov Institute of General Genetics of the Russian Academy of Sciences, Professor Oleg Balanovsky, is covered with numerous markings and has a lot of designations. And each point on it is evidence of an expedition, lasting several weeks, to collect DNA samples from about 100 representatives of the indigenous population of this territory. Research has been conducted for almost 20 years: the first expedition took place in 1997, and there were already more than 50 of them. The collected samples formed a biobank, which today contains over 25,000 samples from more than 250 populations (see map).

This is the world's largest collection of DNA of the indigenous population of Northern Eurasia. The project is simply gigantic, it is carried out with the support of the Russian Science Foundation and provides for the analysis of collected samples using the most modern approach – complete sequencing (genome decoding) of a single chromosome.

– How are these studies conducted, what do genogeographers manage to find out?

– According to the last census in Russia, there are more than 200 peoples and nationalities, many of them consist of various regional populations, – says Oleg Pavlovich. – In order to study the gene pool of the people and to understand the biological reflection of the history of the origin of the people, it is necessary to collect samples of representatives of individual populations, population groups and compare them. This will help determine the composition of the gene pool of the people, find out as a result of what events it was formed, how it changed over time. These are the fundamental issues of genogeography. Even schoolchildren know that the population of Mexico was formed from a mixture of Native Indians and conquerors of the Spaniards. And exactly the same answer was received by geneticists in the 1990s, after analyzing mutations of mitochondrial DNA and the Y chromosome. And due to the fact that mitochondrial DNA is inherited in the female line, and the Y chromosome is inherited in the male line, the "school" answer was supplemented: the Spanish contribution was mainly made by men, and the local one by Indian women. Since then, scientists have been using this promising method to unravel many "knots" in the origin of peoples, especially in the absence of written sources. If we take the history of mankind as a whole, then in the "genetic binoculars" it is best to see its first stages (tens of thousands of years ago). But the closer to modernity, the thicker the "fog" – and we do not know what migration and demographic processes took place.

Genogeography helps to get answers to these and many other questions. It has been developing since the beginning of the last century and has experienced several scientific revolutions. The penultimate one, which occurred at the turn of the century, is associated with the introduction of the Y chromosome into the research of gene pools - the only one that is inherited strictly on the paternal line (from father to son) and is not shuffled in each new generation. It made it possible to turn genetic binoculars into a microscope, revealing differences even between very similar gene pools and detecting traces of recent events. Y-chromosome mutations occur continuously in each generation, so the son is genetically different from the father. This is how a kind of genetic chronicle is formed – a collection of genetic material convenient for analysis, into which all new mutations fit. Now, by comparing the chromosomes of different people, it is possible to establish the common origin of the population. And knowing how fast mutations go, date demographic events in the history of the population. The last revolution in genetics happened three years ago. The possibility of complete sequencing of the Y chromosome has opened up, so today it is possible to study not 10 mutations, as before, but 10 million nucleotides, each of which could potentially mutate. Thanks to this, new mutations began to be discovered not once every few months, but daily and by the thousands.

And if the whole of humanity is represented in the form of a huge, mighty tree, then each person with his Y-chromosome is a leaf, and groups of people descended from not very old ancestors are thin knots. The branches are the ancestors of the millennial age, and the most ancient are the trunks. And if earlier we could distinguish mutations only of the "trunks" and the thickest "branches", then with the advent of this much-needed tool we discover mutations characteristic of the thinnest branches and leaves. It's like looking through an electron microscope instead of old glasses. Now we can find out where individual tribes migrated, where the population grew, and where it fell, and when all this happened.

In the south of Western Siberia there is a group of people who call themselves Siberian Tatars. Historians and ethnographers have various theories of their origin, and genetics, due to the lack of accurate markers, could not contribute before. But today it was found out that the populations of Siberian Tatars who settled in different areas have different origins. Some groups originate from the most ancient population of Western Siberia, the gene pool of others was found in Southern Siberia, and the roots of the third – in the Caucasus. It turns out that the pedigree of the Siberian Tatars was formed as a result of the interweaving of at least a dozen branches.

The method of sequencing the Y chromosome turned out to be even more effective than scientists expected. With the help of the RNF grant, we first examine a small number of samples and discover new mutations, each of which is a marker of a certain branch. After that, we check on a large number of samples of the entire biobank, whether they belong to this particular branch or not. As a result, genogeographic maps of the distribution of each branch throughout Northern Eurasia are compiled.

The research includes several blocks. For example, we were able to determine the rate at which mutations occur. To do this, we studied the genealogy of one of the Kazakh clans. Traditional genealogy ascribes it to one founder and indicates the position of each member of the genus on a common tree. A genetic analysis was carried out – and the genetic tree exactly coincided with the information gleaned from the legends. This genus descended from one ancestor, and knowing from the written annals the time of his life, and from the genetic tree – the number of mutations that occurred after him, it was not difficult to calculate the rate of mutation.

I note that not only the scientists of the Academy strive to clarify the origin of peoples, but also amateur geneticists. They conduct genealogical and genetic research and, by doing some one branch of the Y chromosome, they reach a depth of knowledge in it that a professional will sometimes envy. But at the same time, pseudoscience has blossomed, seriously proving, for example, that Russians are the most true Aryans, because in Russia and in Northern India, the same branch of the Y chromosome is most often found. It is enough for an amateur to forget just two things: that a people is not so much its gene pool (biological) as self–consciousness (social) and that the gene pool is woven like a carpet from many branches of the Y chromosome, as he (an amateur) slips into the sphere of pseudoscience, declaring a branch of the Y chromosome first as a genus, and then as a people. For a long time there was mutual misunderstanding between academic science, as well as civil ("people's") science and pseudoscience, but now there has been a separation, an attempt has been made to put everything in its place. We even managed to establish cooperation with amateur enthusiasts. Together we have prepared an article that we are sending to a leading foreign magazine today. It is dedicated to the ancient trunk of the Y-chromosome tree that still exists on the territory of our country, from which all the Indians of America originated 15-25 thousand years ago. We traced the history of one of the branches of this trunk for 20 thousand years and found out that 4000 years ago one of its branches appeared in Europe, where it is still found today – one variant among the peoples of northwestern Europe, the other among Ashkenazi Jews (see figure).

The illustration shows the sequence of division into smaller branches. For each branch, a map is given with the places of birth of people who are its carriers. If the old branches (green and red) are found only in Asia, then the young ones, starting with the blue one, are also found in Europe, brown – among the Ashkenazi, yellow – among the peoples who settled around the North Sea.

– Is it possible to use the new knowledge you have acquired?

– It is important not only for fundamental science, but its practical application is also possible. For example, for the development of so-called pharmacogenomics. It is known that depending on the genes, the same drug acts differently. To determine its optimal dosage, it would first be necessary to understand the patient's genome, but genome sequencing is affordable for a rare patient. And then knowledge about the gene pools of different peoples can come to the rescue, with what frequency they have certain genetic variants. As a result, for example, Yakuts and Chechens will take the same drug, but in different doses.

Another field of application is criminology. Often, the investigation has no data other than genetic material from the crime scene. But it can be used to find out which territory the alleged criminal belongs to – a very important clue for the investigation. We have several high-profile processes to our credit, for which the instructions of our laboratory staff served as the starting point. The Investigative Committee turns to us for help every month, and if earlier we provided only approximate information, today, largely thanks to the grant of the Russian Academy of Sciences, we are gradually learning to concretize it, clarify it – and thereby we can narrow down the search for a suspect.

– Why, in your opinion, did the RNF give preference to your grant application?

– I think the foundation appreciated how important the use of the Y chromosome is in the study of the human gene pool today, when these studies are in a phase of exponential growth. The funds invested now in the analysis of the Y chromosome will give a 10-fold increase in accuracy when studying the origin of different population groups, which is unattainable in other fields of science or when using other chromosomes.

– Will you continue this project?

– Last year, with the support of the RNF, our article on the gene pool of the Slavs was published. For the first time, it was possible to find out which groups of the population mixed and in what ratio, how the current gene pool of Russians, Poles, and Serbs was formed... The results were somewhat unexpected. The picture appeared as follows: in the modern gene pool of the Slavs, only the top layer can be considered Slavic, like a curl of icing on a cake. And its "filling" – the gene pool – was formed as a result of events that occurred long before the appearance of the Slavs. After all, at the time of the arrival of the Slavs in Eastern Europe or the Balkans, some tribes already lived here. There were a lot of such migrations, and each new migration had an impact on the gene pool, adding another layer to the filling of the cake. We managed to show how thin the layer of Slavic "glaze" is and how powerful the "filling" appears. So gradually we begin to navigate the intricacies of our own history, establishing the facts of a thousand years ago.

And if the RNF, as we hope, extends the grant for another two years, we will be able to sort out the confusing history of the origin of Russians, other Slavic and non-Slavic peoples of Eastern Europe, clearing it of the conjectures of pseudoscience. Let's focus on the branch of the Y chromosome that occurs in every second Russian or Pole, but which is just as common in Altai, Tajikistan, and northern India. I am sure that after three years of hard work on other branches and, as a result, a dozen publications already prepared in leading domestic and foreign publications, we are able to crack this "tough nut". Our main task is not so much to describe the gene pool, but to understand the reasons that cause changes in it.

– Are such studies widespread in the world?

– In Russia, a dozen laboratories use the Y chromosome as a marker, and there are several hundred of them abroad. Our laboratory, largely thanks to the support of the RNF, has entered a narrow circle consisting of four or five leading world teams, mainly from England and the USA, who conduct research on the Y chromosome by full-genome methods and form standards in this field of science.

Portal "Eternal youth" http://vechnayamolodost.ru  18.07.2016