04 March 2015

The ARHGAP11B gene makes the brain human

How Evolution has Enlarged Our Brain

Kirill Stasevich, "Science and Life"Last week, the entire scientific (and not only scientific) world applauded the work of researchers from Duke University who enlarged the mouse brain with human DNA.

Mice were transplanted with a regulatory sequence called HARE5, which was taken from the genome of chimpanzees and humans. HARE5 works as an enhancer (or assistant-stimulator) of the Frizzled 8 gene, on which the division of cortical neuron progenitor cells in the developing brain depends. As a result, it turned out that, compared with the enhancer from chimpanzees, the human regulatory fragment made the brain of mice 12% larger, due to an increase in the number of neurons in the cortex. Maybe it was because of this piece of DNA that man became intelligent?

Maybe not just because of him. A new article has just been published in Science (Florio et al. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion), the "hero" of which was another section of DNA, namely– the ARHGAP11B gene (let's emphasize – not a regulatory fragment, but a gene encoding information about the protein). Wieland B. Huttner and his colleagues from the Institute of Molecular and Cellular Biology and Genetics of the Max Planck Society tried to find out which genes control brain development in human and mouse embryos (A gene for brain size – only found in humans). First of all, the authors of the work were interested in the molecular and genetic differences between the developing brains of humans and the developing brains of rodents.

The convolutions, for which the primate brain is famous, arose relatively late in evolution,
and even rodents don't have them yet. (Photo by EUSKALANATO / Flickr.com .)

Several types of stem cells contribute to the formation of the cerebral cortex, which over time turn into various neurons. And the first task was to separate such cells from each other so that they could be compared in humans and mice. As a result of comparing similar stem cell lines, it was possible to find 56 genes that worked in the human brain, but which were not present in rodents. Among them was one particularly active, the aforementioned ARHGAP11B. It is known about him that he arose due to incomplete doubling of a certain ancestral gene - incomplete in the sense that some part of the original was missing in the copy. (In parentheses, we note that this is the usual way of the appearance of new genes, when an additional variant of an already existing sequence appears, after which one of the variants becomes an "evolutionary polygon", absorbing mutations and acquiring new functions.) Copying of the gene happened after humans split off from monkeys: ARHGAP11B does not exist in chimpanzees, nor, moreover, in rodents, but it does exist in Neanderthals and Denisov people (another extinct subspecies of humans, for the study of which the Russian Academy of Sciences recently awarded its highest award). So the great role of this gene in the "understanding" of a person has been suspected for a long time.

Now, we can say, the suspicions have been confirmed. Transplanted into mice, ARHGAP11B doubled the number of neurons in the cortex; moreover, sometimes mice with ARHGAP11B even began to form convolutions, which, as is known, are completely absent in rodents. At the cellular level, the effect of the gene was to increase the number of intermediate progenitor cells and encourage them to divide more often before they finally turn into specialized neurons.

The brain of a mouse embryo, in which convolutions began to form due to a human gene (right half).
(Photo by Wieland Huttner / Max Planck Institute of Molecular Cell Biology and Genetics.)

Of course, the efficiency of the brain depends not only on the volume, but also on the nature of connections between neurons, on the architecture of neural circuits and large neural "departments". At the same time, it would be strange to deny that the more neurons, the more options for a variety of architectural delights. So we owe our intelligence to a very large extent to the molecular genetic tools that have added nerve cells to us. Now we know two such tools: the HARE5 regulatory element and the ARHGAP11B gene, and it is possible that further research will add other genetic "players" here.

Portal "Eternal youth" http://vechnayamolodost.ru04.03.2015

Found a typo? Select it and press ctrl + enter Print version