Home Science They identify the genes that shaped the human brain

They identify the genes that shaped the human brain

Scientists discover the genetic key that caused the human brain to triple its size.

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Human brain
Human brain

Our thinking organ had to experience an  incredible evolution in a record period but, what was it that gave us this uniqueness? What change boosted our ability to think and solve problems? Now, two researches carried out by the University of California at Santa Cruz (USA) and the Free University of Brussels (Belgium) have revealed that a group of genes found only in humans arose in our ancestors. 3-4 million years and are responsible for having driven the evolution of a brain of just 400 cubic centimeters to 1350. Both studies have been published in the journal Cell.

What genes is it about?

The genes, called NOTCH2NL, belong to a very old (and practically unknown) family called Notch that was identified for the first time in fruit flies. The genes of Notch date back to “hundreds of millions of years” and “play an important role in embryonic development,” says David Haussler, professor of biomolecular engineering at the University of California at Santa Cruz and co-author of the first study.

“Discovering that humans have a new member of this family involved in brain development is extremely exciting,” says Haussler.

The researchers discovered that the NOTCH2NL genes seem to play a key role – and only in humans – in the development of the human cerebral cortex, as the basis of advanced cognitive abilities, such as reasoning and language. The genes are expressed in the neuronal stem cells of the cortex and delay their maturation in specific cell types. This delay results in the accumulation of a larger set of stem cells, which in turn generates the production of more neurons throughout the development of the brain.

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Genes increase signaling during development

The NOTCH2NL genes are found in an area of ​​the human genome, “the long arm of chromosome 1”, which has been linked to several neurodevelopmental disorders such as autism, microcephaly, macrocephaly and schizophrenia.

Some of the disorders are related to the duplication of large sections of DNA, and some are related to deletions (a part of a gene that can cause an abnormality).
The proteins encoded by the Notch family of genes are related to signaling within cells and also between cells. Many of these signals direct the fate of stem cells, for example, if they differentiate into brain or heart cells, in many parts of the body.

The researchers discovered that NOTCH2NL genes encode proteins that “improve” Notch signaling.

“Notch signaling was already known to be important in the developing nervous system, and NOTCH2NL appears to amplify Notch signaling, which leads to increased proliferation of neural stem cells and delayed neuronal maturation,” adds Sofie R. Salama, scientific researcher in biomolecular engineering at UC Santa Cruz.

However, experts point out that genes are just part of a much larger process that controls the development of the human cortex: they do not “act in a vacuum”. They came into play in a “provocative moment of human evolution”.

It seems that “DNA copy errors” that occurred in our ancestors and that gave rise to the NOTCH2NL genes are of a type similar to those leading to neurological disorders in the 1q21.1 deletion / duplication syndrome.

These long segments of DNA – which are almost identical – can confuse the machinery of replication and cause instability in the genome,” explains Haussler. Paradoxically, it seems that the process of gene duplication in the region of chromosome 1 that gave us a larger brain may also be responsible for making us vulnerable to the 1q21.1 deletion / duplication syndrome.

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Using sequencing tools, the researchers found eight versions of NOTCH2NL in humans today and suspect there is more to discover. Each version of NOTCH2NL varies slightly in the sequence of its DNA, but at what level it remains a mystery.

The genes showed subtle differences when tested in cells cultured in the laboratory. However, there is still much more work to be done to discover what these differences mean.

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