Neanderthal genome: details

The Neanderthal was read in its entirety
Artem Tuntsov, "Newspaper.Ru»Scientists have presented the first results of the complete decoding of the Neanderthal nuclear genome.

They could talk, couldn't stand the dairy diet, and couldn't transmit microcephaly and Alzheimer's disease to us. However, the most interesting thing awaits us in the official publication of the genome, geneticists hinted.

On Thursday evening, during a press conference in Leipzig, Svante Peebo could not sit quietly on a chair and continuously shook his knees. The Swedish professor, director of the genetics department of the famous German Institute of Evolutionary Anthropology, spoke about the results of the project of decoding the genome of the Neanderthal, the beginning of which he himself determined in the middle of 2006.

In fact, this story can be traced at least a dozen years further into the past. In the late 1990s, Peebo and his collaborators managed to read several tiny fragments of DNA extracted from the remains of the closest extinct relative of modern man. Just a few years earlier, the Swede's colleagues would have considered such a task impossible – too quickly the main biological molecule decomposes after the death of its carrier, and too quickly its place is taken by the DNA of hundreds and thousands of species of bacteria and fungi, which immediately begin processing bones into material for a more primitive life.

But Peebo's plan succeeded. First, scientists identified all 16.5 thousand nucleotides in the mitochondrial genome of a Neanderthal man who disappeared 30 thousand years ago, then they showed that they were able to decipher several million genetic "letters" from his nuclear DNA, which is not inferior to human DNA. And then they systematically took up the decoding of the complete nuclear genome.

On Thursday, Peebo announced that the first stage of work has been completed: more nucleotides have already been read than the full length of the genome (3.7 billion vs. 3.2).

On the day of the 200th anniversary of Darwin, the scientist felt entitled to slightly violate unwritten scientific ethics by telling journalists about his work before it was published in a peer-reviewed scientific journal. However, the most "delicious", the geneticist hinted, he and his colleagues left for an article in Science, which should be published in the coming months.

PurityThat 20% more nucleotides have been read than there are in the genome should not be confusing – it's just that some sections of DNA have been read in several copies.

Geneticists generally like to read each place 10-20, or better, 30-40 times, in order to guarantee the detection of sequencing errors that inevitably occur during the reading process. This multiplicity is called the average depth of coverage.

A bone sample of a female Neanderthal, from which the greatest amount of genetic information was read. The numbers indicate the proportion of hominid DNA in the total volume of genetic material (the rest is the DNA of microorganisms that inhabited the bones after the death of a person). Note that these values vary greatly from place to place. // eva.mpg.de

In the case of a dilapidated Neanderthal genome, a large depth is especially relevant, but so far, instead of covering 30-40, scientists have barely reached 1.2. Moreover, in reality, they have managed to see only 63% of the Neanderthal genome by now, so DNA has been studied very unevenly: 37% of its length (approximately 1.2 billion nucleotide pairs) we have not they have never been seen, and the remaining 63% (2 billion pairs) – on average twice.

The most important thing was to make sure that the DNA under study belongs to Neanderthals, and not to hundreds of researchers who have been studying the structure of Neanderthal bones for decades, holding them in their hands.

To assess the degree of contamination, scientists used two methods – fragments of the Y chromosome and fragments of the mitochondrial genome. The main part of 3.7 billion nucleotides were read from female bones. There should be no Y chromosomes in the genome of a woman, even a Neanderthal one, at all, and for Neanderthal mtDNA we know 133 differences from human mtDNA. According to these signs, scientists estimate the degree of pollution at 0.2–0.5% "and in any case less than 1-2%," says Peebo.

However, even those samples that were not touched by man are quite to the taste of fungi and bacteria. To isolate 3.7 billion "letters" of the Neanderthal genome, scientists had to read more than 100 billion pairs of nucleotides: in the best fragments of the best samples, the proportion of DNA of interest only slightly exceeded 4%. If these bones were clean, the multiplicity of reading the Neanderthal genome would now be more than a decent 25-30 times. However, it is relatively easy to distinguish the DNA of fungi and bacteria.

SamplesSelecting a suitable source of genetic material, Peebo and his colleagues sorted over 200 samples from 70 samples found in 16 different locations in Europe and Central Asia.

And most of them were rejected – it was almost impossible to prove the absence of contamination of human DNA.

As a result, the scientists settled on four sources. The lion's share of the data (more than 99%) was obtained by analyzing DNA from Neanderthal bones found in the Croatian Vindija cave. First of all, a piece of a woman who died 38 thousand years ago, which has not yet seemed particularly interesting to anthropologists, and therefore has remained almost untouched by a modern type of person.

In addition to the Croatian Neanderthal, Peebo and his colleagues read 5 million pairs of nucleotides in the bones of a Neanderthal from the Spanish cave El Sidron. At the request of geneticists, in order not to enter their DNA into the samples, archaeologists in the cave worked in special biological protection suits and frozen bones immediately after extracting them from the ground, where they had lain for 43 thousand years.

The third Neanderthal was a child from the Mezmay Cave in the Krasnodar Territory, whose tissue samples were provided by anthropologists Lyubov Golovanova and Vladimir Doronichev from the St. Petersburg Laboratory of Prehistory. To date, 20 million pairs of nucleotides have been read from the bones of a Neanderthal man who died at the age of just a couple of weeks. Scientists have special hopes for this baby: it is much older than the rest of the samples (the age of the bones is estimated at 60-70 thousand years), and its study will be able to shed light on the development of the Neanderthals themselves.

Svante Peebo managed to get even a piece of a Neanderthal with a capital letter – the same person found in the valley of the Neander River, who identified the entire species and gave it a name.

Scientists have read 2 million pairs of nucleotides from a bone fragment stored in a museum in Bonn. The age of the sample is about 40 thousand years, of which 150 he spent in the museum.

Excellent NeanderthalsWith the help of 2 billion (if we exclude repeating fragments) "letters" of the genetic code, scientists confirmed the results of three years ago, obtained on a thousand times smaller material.

The DNA sequences of Homo neanderthalensis and H. sapiens of the modern type coincide by almost 100%.

In such cases, it is more convenient to consider the differences themselves not in absolute terms, but in relation to the difference between a modern person and his closest surviving relative – a chimpanzee; we share 99% of DNA with them.

The difference between the Neanderthal genome and the reference human genome is 12.8% of the difference between humans and chimpanzees. But do not think that "Neanderthals are one–eighth monkeys." These 13% completely fit into the framework of the variation of the human genome in the population as a whole. For example, among the French alone, this variation accounts for 8.1% of the difference between a human (more precisely, the reference genome) and a chimpanzee. Among the Chinese, the variation is 8.6%, among the Bambuti pygmies – 10.5%. But no one claims that the French are monkeys by 8%, and Africans by 11%.

Integrally, according to the genome, Neanderthals are almost indistinguishable from us. But the devil, as you know, is in the details, and it is to the numerous details that Peebo and his colleagues have devoted the articles that are currently in the process of reviewing. The head of the works revealed some of the secrets, stipulating that he would not "take too much away from the article yet," referring to the fact that he could not tell the journalists everything and had to leave something for the article.

For example, the chief geneticist of the Leipzig Institute immediately refused to confirm or deny the rumors creeping from conference to conference about the discovery of a genetic inversion on the 7th chromosome of our distant relative. In humans, such an inversion leads to a rare syndrome, sometimes ending with inhibited brain development and slight underdevelopment of the fingers. The project manager did not speak on this topic.

However, in the 63% of the Neanderthal genome now known to us, several other very interesting genes have fallen. For example, Foxp2, which is often called the "speech gene". Mutations in this gene usually result in an inability to control their speech apparatus and perceive words (despite the fact that otherwise such "mutants" remain normal people). Thus, Foxp2 is somehow connected with speech, although it is clear that a single gene cannot be responsible for such a complex structure as human speech - the TV won also stops working, even if only one chip burns in it.

A fragment of the foxp2 gene in chimpanzees, modern humans and two Neanderthals. In humans, there are two non-synonymous nucleotide substitutions of the 7th exon of the gene in comparison with its monkey variant. The same substitutions are also visible in the genome of a Neanderthal, one in both positions, the other in at least one. // eva.mpg.de

It is known that the human version of the Foxp2 protein differs from the chimpanzee in two positions, and a little more than a year ago, scientists managed to "get" into this gene by reading only 2% of the genome of the Spanish Neanderthal (probably the same 5 million pairs of nucleotides from the El Sidron cave, which were discussed above). Then it turned out that the same two "human mutations" are present in the Neanderthal from El Sidron. As Peebo said on Thursday, at least one of these substitutions is also present in the genome of the Croatian Neanderthal; the second one did not get into the coverage area. So Foxp2 could not prevent either the Neanderthal or our common ancestor from speaking. Unless Foxp2 appeared in Neanderthals due to interbreeding with humans.

According to Peebo, the question of the transfer of genes by a modern type of man to a Neanderthal is still open. We can only say for sure that the Lct gene of the lactase enzyme, thanks to which most of the inhabitants of Europe can drink milk not only in infancy, we did not transmit to Neanderthals – those individuals whose bones were inherited by Peebo did not have such an ability. However, this is not surprising: according to modern estimates, it appeared in humans themselves 10-20 thousand years ago, when the Neanderthals in Europe disappeared.

In the opposite direction – from a Neanderthal to a human – there was no gene transfer. The scientist stated that at the moment it is safe to say that there are practically no Neanderthal genes in humans and, although he cannot give an accurate assessment yet, the share of Neanderthal heritage in the human genome, "if there is, is negligible." Previously, this was shown for the mitochondrial genome, now for the nuclear one.

In particular, the Neanderthals did not pass on to us the genes of microcephaly, which is much more common in the descendants of Europeans who lived side by side with H. neanderthalensis than in Africans. It was not from them that we got the genes of the t-protein, the formation of tangled filaments of which ends the amyloid cascade in Alzheimer's disease.

However, archaeologists, who are much better than geneticists can understand the relationship of human tribes based on the material evidence left from them, and so do not see any indication of the possibility of interbreeding in the past between our direct ancestors and Neanderthals.

Neanderthal for manMeanwhile, Peebo is already trying to investigate the question of interbreeding between the Neanderthal and its possible predecessors in Europe.

Whether there were such or H. neanderthalensis became the first colonizer of the "old lady" – we do not know yet.

The scientist promised that many more interesting results on the Neanderthal genome will be published in the coming months. And while the editorial process is underway, scientists are working like clockwork. Peebo set a goal to achieve 15-20-fold coverage of the genome, which will create a reliable base of differences between Neanderthals and humans.

After that, Neanderthal genetics will be able to become personal, as human genetics has become in recent years. And scientists will be able to understand how diverse our relatives who have sunk into oblivion were. The mtDNA data of 6 individuals of H. neanderthalensis obtained during the decoding of the nuclear genome as a by-product, so far do not indicate in favor of these ancient people. Their genetic diversity does not reach the diversity of humanity, although it is quite at the level of its individual races.

Perhaps the history of the settlement of our predecessor was very similar to ours. Only they left Africa once and did not go further than western Eurasia.

Data on the differences between our closest extinct relatives from us and from each other will help to understand our own history. They will highlight the genes that for the last hundreds of thousands of years, after the separation of species, were influenced by positive selection and helped to achieve the dominant position on the planet that we now occupy. In the end, it is in order to understand ourselves that we study this story.

Portal "Eternal youth" http://vechnayamolodost.ru/13.02.2009