Genes That Make Us Humans: Brain Development

 

Humans underwent a series of rapid evolutionary changes that allowed us to grow bigger brains, with more neurons devoted to the outer cerebral cortex – the area responsible for higher order cognitive reasoning. In fact, human brain size nearly quadrupled in the six million years since Homo sapiens last shared a common ancestor with chimpanzees.

However, many of the genetic tweaks which enabled these changes are now associated with disorders such as autism and schizophrenia, according to recent research.

For example, in 2018, two teams of researchers identified a gene family, Notch2NL, that appears to play an important role in cortex development in humans, and may have been a driving force in the evolution of our large brains.

The Notch signalling pathway is an ancient system used in all animals to control the fate of stem cells in the embryo, directing whether they divide and grow to form new stem cells, differentiate into more specialised cells, or die. However, the specific Notch2NL gene is found only in humans, and is absent from the DNA of chimpanzees, orangutans, and other great apes.

"What's fascinating about the history of Notch2NL is that there actually was an original event that happened in our common ancestor with gorilla, where the original Notch2 gene was duplicated," says Sofie Salama, professor of molecular, cellular and developmental biology at the University of California Santa Cruz, who was involved in one of the research studies.

Segmental gene duplication is a process by which a section of the genome gets copied. The new copy is then moved to another spot in the genome, leaving behind two very similar sections of DNA.

"It seems based on our analysis that that initial duplication event was kind of like a dead-on-arrival thing, and that the new gene either couldn't get expressed, or created an unstable protein," says Salama.

Then in the human lineage around three to four million years ago the gene was altered again through a process known as gene conversion. This time the new copy – Notch2NL – was functional.

"That is an interesting time in our evolutionary history, because if you look in the fossil record that was right before there was this exponential increase in brain size," says Salama.

So how could Notch2NL lead to bigger brains? The gene delays stem cells in the cortex of the brain from turning into neurons. Instead, the stem cells carry on dividing and producing more stem cells. This ultimately leads to more neurons being produced, and bigger brains.

The publishing continues...

- Author: Jasmin Fox-Skelly, BBC