Our thinking organ had to undergo an incredible evolution in a record period, but what was it that gave us this uniqueness? What change prompted our ability to think and solve problems? Now, two investigations 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 ago 3-4 million years ago and they are responsible for driving the evolution of a brain from just 400 cubic centimeters to 1,350. Both studies have been published in the journal Cell.
What genes is it?
The genes, called NOTCH2NL, belong to a very old (and largely unknown) family called Notch that was first identified in fruit flies. Notch genes date back “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, Santa Cruz and co-lead author of the first study.
“Finding out that humans have a new member of this family involved in brain development is extremely exciting,” says Haussler.
The researchers found that NOTCH2NL genes appear to play a key role – and only in humans – in the development of the human cerebral cortex , as the basis for advanced cognitive skills such as reasoning and language. Genes are expressed in the neuronal stem cells of the cortex and delay their maturation into specific cell types. This delay results in the accumulation of a larger pool of stem cells, which in turn generates the production of more neurons throughout brain development.
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 gene family are related to signaling within cells and also between cells. Many of these signals direct the fate of stem cells, for example, whether they differentiate into brain or heart cells in many parts of the body.
The researchers discovered that the NOTCH2NL genes encode proteins that “enhance” Notch signaling.
“Notch signaling was already known to be important in the developing nervous system. NOTCH2NL appears to amplify Notch signaling, leading to increased neural stem cell proliferation 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 at a “provocative moment in human evolution.”
It appears that the “DNA copy errors” that occurred in our ancestors and that gave rise to the NOTCH2NL genes are of a similar type to those that lead to neurological disorders in the 1q21.1 deletion / duplication syndrome.
“These long segments of DNA – which are almost identical – can confuse the replication machinery and cause instability in the genome, ” explains Haussler. Paradoxically, it appears that the gene duplication process in the region of chromosome 1 that provided us with a larger brain may also be responsible for making us vulnerable to 1q21.1 deletion / duplication syndrome.
Using sequencing tools, the researchers found eight versions of NOTCH2NL in humans today, and they suspect there is more to discover. Each version of NOTCH2NL varies slightly in its DNA sequence, but at what level remains a mystery.
The genes showed subtle differences when tested in cells grown in the laboratory. However, there is still much more work to be done to find out what these differences mean.
Reference: Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis. Cell (2018). DOI: 10.1016 / j.cell.2018.03.051
