Why is the human brain two complicated

Evolution and brain development : Mutations enlarged the human brain

The human brain is about three times the size of that of its closest relatives in the animal kingdom. Two research teams have now apparently found the cause of this increase. They describe their findings in the journal "Cell" (second work here). According to this, a gene variant found only in humans stimulates stem cells in the brain to more division steps in embryonic development, so that they only grow relatively late, but into much more nerve cells than in great apes.

"One of the holy grails of researchers like us is to find out what is responsible for a larger brain during human development," says Pierre Vanderhaeghen from the Université Libre in Brussels. His group looked for genes that are unique to humans and that are active in brain development. She found 35 candidates from a total of 23,000 hereditary factors, including “Notch2NL”.

“Notch” genes are evolutionarily very old genes found in many animals. They are involved in signal transmission and development processes. “Notch2”, for example, plays a crucial role in the development of organs such as the brain. Only humans have a special variant of this gene, Notch2NL, which also occurs three times in the human genome.

More stem cells, more nerve cells, more brain

When David Haussler's research team from the University of California at Santa Cruz switched off these genes in brain stem cells in cell culture using a genetic technique, the stem cells matured into nerve cells more quickly. As a result, however, fewer stem cells remained, so that fewer nerve cells were created overall. In embryonic development, the Notch2NL genes ensure that the stem cells divide more frequently and remain stem cells longer before they mature into nerve cells: more stem cells form more nerve cells, the brain becomes larger. This is especially true for the cerebral cortex - that area of ​​the brain that is disproportionately enlarged in humans compared to great apes.

Apparently the Notch2NL genes were created by duplicating a more original Notch gene - at the time of the development of hominids about three million years ago. However, this natural, random genetic optimization had its price. “On the one hand, this evolutionary change in the genome favored the formation of a larger cerebral cortex, but on the other hand it also increased the risk of spontaneously occurring genetic changes that can ultimately be associated with diseases such as schizophrenia or autism,” says neurobiologist Oliver Brüstle from the University Hospital Bonn. "In accordance with the assumed role of the Notch2NL gene family in the evolutionary increase in the size of the brain, a different size of the brain can also be determined in these patients."

A copy of the gene is missing in autistic people

In fact, Haussler's team discovered that only two of the three Notch2NL genes were present in three patients with autism. Their brains were somewhat reduced. In three schizophrenia patients with enlarged brains, however, they found four instead of three Notch2NL genes.

That the notch genes are the only drivers for the development of the great brain of homo sapiens have been, but is unlikely. "During human evolution, a large number of genetic changes have occurred that are relevant for brain development and function," says Brüstle. "This understanding is important in order to counteract expectations or fears that, for example, artificial insertion of individual genes can easily induce 'humanization' in animal models." It should therefore not be possible to breed animals with human-like brain functions for the time being. (with dpa / smc)

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