We are all a bit Neanderthal

Neanderthal genome read: Neanderthals left a mark in the genes of modern humans Elena Naimark, "Elements"

Scientists working within the framework of an international project to read the nuclear genome of a Neanderthal have completed the decoding of a significant amount of information. They have identified the most important genes that distinguish homo sapiens from their closest hominid relative, the Neanderthal. And moreover, it was possible to reliably confirm the version about the crossing of Neanderthals with ancient Europeans.

In 2006, a project to read the genome of Neanderthals (Neanderthal genome project) was launched. The head of this ambitious and promising project Svante Pääbo from the Max-Planck Institute for Evolutionary Anthropology in Leipzig promised to report on the results of the work in 2 years, but as we can see, it took him 3.5 years. But the results of the study were unexpected not only for the public, but also for the researchers themselves. Despite their own bias, geneticists have proved that ancient Sapiens still interbred with Neanderthals.

Whether Sapiens were able to interbreed with Neanderthals or not – this question has always caused heated debate. There were arguments both in favor of crossing and in favor of pure lines; both morphological and genetic criteria were used. The main argument of the supporters of pure lines was the absence of traces of hybridization of mitochondrial DNA of Sapiens and Neanderthals. Adherents of the crossing of Neanderthals and Sapiens appealed, for example, to elegant studies of the divergence of the microcephalin gene. But all the arguments were indirect, and, as always happens with indirect arguments, they only warmed up the opponents, not convincing anyone in particular. Everyone was waiting for the results of reading the nuclear genome of Neanderthals.

The study material was bones from a cave in Croatia; the age of the samples was estimated by radiocarbon method as 38,000 and 44,000 years, since the samples were extracted from different layers of the cave. (I note here that mitochondrial analysis showed a high identity of samples with different ages, so presumably their owners were close relatives. Then what to do with age determination? Scientists have not yet commented on this contradiction.) Specific bones were chosen, in particular, due to the fact that archaeologists were not too interested in them before, so they did not have time to grab them with their hands and make a fair share of their own DNA.

Geneticists immediately managed to prove that they were not dealing with the remains of Neanderthal men, as archaeologists assumed, but with the bones of three Neanderthals. Reading the first sections of the genome prompted researchers to think that there was no crossing, since no traces of hybridization were found.

And finally, 2/3 of the genome has been reconstructed and cleared of contamination and errors – this is about 4 billion nucleotides. To get a record of the Neanderthal genome, it was necessary to throw out of consideration the entire microbial component of the material: it is clear that it was microbes that turned out to be the most numerous "pollutants" of ancient remains. This work turned out to be extremely time-consuming and in many ways innovative (it is described in detail in a separate article in Science, see: Targeted Investigation of the Neandertal Genome by Array-Based Sequence Capture).

To separate the human component from the microbial one, libraries of known microbial genes were first used and excluded. Then the Neanderthal samples were treated with special enzymes that destroy only microbial genes. As a result, there are not so many microbial genes left in the samples. Next, the presence of any mammalian genes was evaluated taking into account all available information in modern bioinformatic libraries. Geneticists also appreciated the introduction of genes of modern people – yet these samples have been in the hands of researchers. According to mitochondrial DNA, it is possible to judge the volume of these contaminants – about 1%.

It should be emphasized that only the development of genomics and the creation of global libraries with accessible and unified information made such work possible. The more carefully you read the methodological part of the work, the clearer the fantastic possibilities and stunning prospects of this new field of science become.

The genome of Neanderthals and modern humans differs by 0.16%. On the one hand, the differences are small. On the other hand, it is possible to see exactly which different genes make up our "intelligent" essence – in other words, which genes are present in modern humans, but are absent in both chimpanzees and Neanderthals. These are hypothetical elements that are not inherited from a common ancestor and appeared only after the divergence of the branches of modern man and Neanderthal. There were 78 such purely modern elements – nucleotide substitutions in genes. Some of these nucleotide substitutions may be neutral (they may have been fixed as a result of normal demographic processes, bottlenecks, etc.), while others may have adaptive significance.

So, there were 5 such genes that carried several of these nucleotide substitutions. These genes and, accordingly, these mutations are obviously adaptive for modern humans, otherwise evolution would not have paid such close attention to them. These are genes related to skin functions, mental activity, and energy metabolism (see the article in Science Targeted Investigation of the Neandertal Genome by Array-Based Sequence Capture).

It should be noted that there were also such mutations that Neanderthals had, but were absent in humans and chimpanzees. Their functions are unknown. The genes that are present in the genome of Neanderthals in a clearly larger number of copies than in modern humans have also been identified. Their purpose is also still unknown. Geneticists and bioinformatics will obviously not be out of work in the next ten years.
 

Fig. from the discussed article in Science Close Encounters of the Prehistoric Kind

The most remarkable results were obtained when comparing the reconstructed genome of Neanderthals with the gene sequences of 5 modern humans – a European, a native Chinese, a resident of Papua New Guinea and two indigenous Africans from South and West Africa.

According to the level of genetic differences, the Neanderthal genome turned out to be more similar to Europeans, Asians and Papuans than to Africans. This clearly follows from the results of a pairwise comparison of the genes of Neanderthals and modern representatives of different parts of the world. Here additional data on modern people were involved to level out individual and demographic differences. The scientists selected for comparison only those genes that carried advanced variants of alleles compared to chimpanzee variants.

The differences between the genes of Neanderthals and one of the nationalities, say Europeans, and between Neanderthals and the next nationality, for example Chinese (Asians), were evaluated. Then the differences between the selected pair of modern people (in this example, between Europeans and Asians) were calculated. After that, it remained to assess the difference between Neanderthals and modern humans, on the one hand, and the chosen modern couple, on the other. If advanced genes occur with the same frequency in Neanderthals and two other peoples and do not differ from the level of differences between the modern pair, then the overall level of differences will be 0. If Neanderthals differ more from one of the peoples than from the other, then the overall level of differences will deviate from zero towards the pair that includes this nationality.

This method of analysis was used for the first time and gave remarkable results. It turned out that Neanderthals, Europeans and Asians and Papuans have more advanced alleles. But Africans showed less similarity with all these samples. So the inhabitants of modern Eurasia have about 1-4% of Neanderthal genes, and there are significantly fewer Neanderthal traces in the genome of Africans.

The conducted statistical research of genetics was supplemented by another interesting fact. Previously, it was shown that among the ancient variants of alleles there are those that are significantly more common in Europeans than in Africans. A total of 13 such geographically capricious variants were known. So it turned out that 10 of these 13 options are also available to Neanderthals!

The figure from the article under discussion in Science A Draft Sequence of the Neanderthal Genome shows possible scenarios of Neanderthal encounters with sapiens, as a result of which the genome of the Eurasian population was enriched with Neanderthal genes.

The scientists settled on scenario 3. Its advantage is the logical presence of Neanderthal genes in the inhabitants of Papua New Guinea. Scenario 2 (interbreeding of late Neanderthals with early Europeans and subsequent gene drift) is less likely, since Neanderthals are equally close to Europeans, Asians, and Papuans.

These very non-trivial results of genetics and statistics leave scientists with no other choice but to allow the crossing of the inhabitants of ancient Europe and Asia with Neanderthals. At the same time, there was no crossing of Neanderthals with the ancient African population. A hypothetical scenario could be the following.

The first meeting of Neanderthals with sapiens could have occurred about 80,000 years ago in Asia. By this time, the first wave of Sapiens migration from Africa had already passed, and Neanderthals approached the Asian borders. Let's recall the locations of Mount Carmel – the famous caves of Shul and Tabun – as well as Kafzeh, where the remains of modern-type people and Neanderthals alternate. The change of anthropological finds and artifacts marks the waves of migration of modern humans and Neanderthals and indicates the time of their possible meeting.

According to Israeli experts, the hypothetical time of coexistence of modern humans and Neanderthals in the vicinity of Mount Carmel could last about 10,000 years. This is quite enough so that the probability of crossing is not considered vanishingly small. Rare but fruitful meetings of Sapiens and Neanderthals have left a mark on the genome of modern humans. The next wave of Sapiens migration from Africa to Europe began about 50,000 years ago. Migrants must have met Neanderthals on their thousand-year journey. It is not known whether marriages between sapiens and aborigines were frequent, but traces of these marriages remained in the genes of modern humans.

Migrations of people across the vast territories of Asia, settlement on the islands of Southeast Asia, together with the drift of genes among the Eurasian population, ensured the spread of the Neanderthal heritage. No matter how scanty this legacy may be, it is still impossible to say without some philosophical reservations that the Neanderthals are completely extinct.

Sources:
1) Richard E. Green et al., A Draft Sequence of the Neandertal Genome // Science. 7 May 2010. V. 328. P. 710–722. DOI: 10.1126/science.1188046.
2) Hernán A. Burbano et al., Targeted Investigation of the Neandertal Genome by Array-Based Sequence Capture // Science. 7 May 2010. V. 328. P. 723–725. DOI: 10.1126/science.1188046.
3) Ann Gibbons. Close Encounters Of the Prehistoric Kind // Science. 7 May 2010. V. 328. P. 680-684 (popular article with lyrical digressions).

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11.05.2010