Do we owe our great brain to these genes?

NOTCH2NL gene family drives brain growth and is active only in humans

The big brain makes us humans unique. But which genes are the underlying? © Fiddes et al./Cell
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Drivers of Evolution: A gene family on the first chromosome could be responsible for a unique human trait: our big brain. As two research teams have discovered, this NOTCH2NL gene family is only functional and particularly pronounced in our country. Their activity promotes the formation of additional brain cells and thus the growth of the cerebral cortex. You could have been the driver for the brain growth of our ancestors, the researchers in the journal "Cell".

We humans have an abnormally large brain in relation to the body - this is considered the basis of our intelligence. But what enabled brain growth in our ancestors? It seems clear that a better energy supply to the mind has played a role, for example, through more starchy and perhaps also cooked food. But what biological mechanisms were the driving force behind this growth in size has remained unclear.

Gene family only active in humans

Now two groups of researchers have found a possible answer. David Haussler of the University of California at Santa Cruz and his team compared their gene expression in humans and macaques in their study, with special emphasis on the regulation of neuronal stem cells.

It turned out that a whole gene family, the so-called NOTCH2NL complex on the first chromosome, is active in human brain cells, but not in monkeys. Even with orangutans, chimpanzees and gorillas researchers found only a truncated, inactive version of this gene group. According to their findings, the NOTCH2NL gene family was repaired by our ancestors about three to four million years ago and duplicated several times.

Path to the human brain: development of the NOTCH2NL gene family © Fiddes et al./Cell

More brain cells through copied genes

The interesting thing is that the NOTCH genes are key factors for organ growth in almost all animals, including humans. The role of the typical human NOTCH2NL family in brain development has been investigated by the second team of researchers headed by Pierre Vanderhaeghen of the Free University of Br ssel. They implanted human NOTCH2NL genes into mouse embryos and observed how this affected brain development. display

And indeed: The number of neuron progenitor cells in the brain of the animals increased significantly. In cultures of human brain stem cells, the scientists then did the opposite test: they removed this gene group from the genetic material of some cells and allowed them to grow into organoids. It turned out that without NOTCH2NL the protons developed faster, but remained small.

Unique human

According to both research teams, this suggests that this gene family may be a key factor in human brain growth. "The multiple duplication of the NOTCH2NL genes and the typical human endowment with this gene family indicates that they are key regulators of human brain size and function, " says Vanderhaeghen. "Fewer copies of NOTCH2NL result in lower brain size, while more copies cause brain growth."

However, some questions are still open, as the researchers emphasize. Thus, the exact mechanism by which the NOTCH2NL genes stimulate brain growth is still unknown. In addition, there are other genes that could play a role: "Excitingly, there are other human-specific genes with unknown functions in the same genetic region, " says Vanderhaeghen. "It will be interesting to see if they may control other aspects of brain development." (Cell, 2018; doi: 10.1016 / j.cell.2018.03.067; doi: 10.1016 / j.cell.2018.03.051)

(Cell Press, Flanders Institute for Biotechnology, 01.06.2018 - NPO)