The evolution of larger brains over the past three million years is the basis for man’s ability to solve complex problems, such as reading this text. The genetic changes that drove the expansion of our mind, however, have been largely puzzling.
That could have changed now: Two research teams from the US and Belgium, led by David Haussler (University of California, Santa Cruz) and Pierre Vanderhaeghen (Free University of Brussels), have located and analyzed a gene family that seems to play a key role in the development of the human cerebral cortex. These three nearly identical genes, which are summarized under the name Notch2NL, could represent the driving force behind the massive size of our brains, the scientists write in the journal Cell.
As the American team found in the comparison of gene expression of humans and macaques, the Notch2NL genes on the one hand slow down the differentiation of cortical stem cells into nerve cells, which leads to the production of more neurons in the course of development. The genes are reserved exclusively for humans. They are completely absent in orangutans, and our closest living relatives, the gorillas and chimpanzees, have only truncated, inactive variants of these genes.
Previous reports on the location of the Notch2NL genes in the human genome was misinformed, as the researchers noted when they investigated mutations of known neurological disorders for association with the genes found. Indeed, these are in exactly the place of the genes whose mutations are associated with diseases such as autism and ADHD. If the genes are present, for example, due to mutations in too few or too many versions, the affected person may develop micro- over macrocephaly.
Notch2NL, the gene family, first appeared three to four million years ago, according to the other study, written by Vanderhaeghen and colleagues — that is near the stage when fossils show a dramatic enlargement of the brains of human ancestors.
For their study, researchers implanted mouse embryos with human Notch2NL genes and observed how this affected brain development. And indeed: The number of neuron progenitor cells in the brain of the animals increased significantly. For Frank Edenhofer, a genomic scientist at the University of Innsbruck, who was not involved in the investigations, they suggest that “the human species has to pay a high price for accelerated brain development – in the form of a genomic compromise”. Notch2NL may increase the fetal development of the brain, but at the same time increase the likelihood of unwanted genomic changes that predispose people to neuropsychiatric developmental disorders.