19 June 2020

Mini-brains with Neanderthal genes

Miniature copies of the brain were grown from stem cells with Neanderthal genes

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From stem cells interspersed with Neanderthal DNA, scientists have created miniature copies of the brain and other organs in order to study the work of their genes. The results of their research were published by the scientific journal Stem Cell Reports (Dannemann et al., Human Stem Cell Resources Are an Inroad to Neandertal DNA Functions).

"Some variations of Neanderthal genes are often found in the inhabitants of Northern Europe. Due to this, their stem cells often contain genes, both copies of which were inherited from Homo neanderthalensis, including those areas associated with skin and hair color. We have shown that this can be used to study the influence of these DNA sites on the development of the human brain," said one of the authors of the work, paleogeneticist Grayson Camp.

The decoding of the Neanderthal genome, which was conducted in 2009 by scientists led by Svante Paabo, director of the Institute of Evolutionary Anthropology in Leipzig (Germany), showed that Neanderthals had contact with our ancestors and left 2 to 4% of their genes in human DNA. Some of these genes, according to scientists, helped our ancestors adapt to life in the north.

Further study of Neanderthal DNA showed that their population was quite small. Therefore, many scientists assume that Homo neanderthalensis died out not because of lost competition with Cro-Magnons, but because of genetic degeneration and the fact that they "forgot how" to adapt to new living conditions.

Moreover, anthropological and archaeological studies of recent years show that Neanderthals were not inferior to the first Homo sapiens in intellectual, technological and cultural development. Therefore, scientists doubt that the reason for the extinction of the first inhabitants of Europe was that they lagged behind modern humans in this regard, and therefore they are trying to learn more about the genetic differences between Homo neanderthalensis and Homo sapiens.

Secrets of the Neanderthal brain

In particular, in the spring of 2018, Paabo and other leading paleogeneticists of the world said that they want to grow miniature copies of the Neanderthal brain by embedding fragments of their DNA into human stem cells. Today, Paabo and his colleagues have published the first results of these experiments, as well as a more convenient method of conducting them.

Analyzing one of the largest genetic databases in which the genomes of reprogrammed stem cells are stored, scientists noticed that many of them had two copies of those genes that we supposedly inherited from Neanderthals. After analyzing their distribution, scientists found that such gene variations were most often found in residents Northern Europe and people from this region.

In total, paleogeneticists isolated 173 cultures of similar cells. They secured the consent of their owners to experiments on growing organoids – miniature likenesses of various organs from similar stem cells, and followed how such mini-organs grew and developed.

In particular, scientists have grown peculiar copies of the brain, in the cells of which there were Neanderthal versions of the BNC2 gene, which determines skin color, as well as receptors from the TLR and OAS families responsible for the work of innate immunity. In total, Camp, Paabo and their colleagues tracked changes in the activity of about 535 genes that were associated with inclusions of the Neanderthal genome in the DNA of cells of these organoids.

Further experiments and the creation of new lines of "Neanderthal" stem cells, as scientists hope, will help them learn about other differences in the work of the genomes of Homo sapiens and Homo neanderthalensis. In addition, scientists want to conduct similar experiments with reprogrammed stem cells of Oceania residents, whose genome contains an unusually large number of DNA fragments of Denisovans – representatives of another related species, traces of which scientists found in the Altai Denisova cave.

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