The question of how the human brain became so large and complex, compared to that of our closest relatives, the primates, has fascinated scientists for decades. Now, a new study sheds surprising light on the matter, demonstrating that a single fragment of human DNA, when inserted into the genome of a mouse, can lead to a significant enlargement of its brain. This represents a major advance that paves the way for a better understanding of our brain evolution.
A DNA Fragment That Boosts Brain Growth
At the heart of this discovery lies a small piece of DNA called HARE5. This fragment belongs to a family of sequences called “human accelerated regions” (HARs), segments of the genome that have evolved very rapidly in humans, unlike other mammals. These HARs are suspected of playing a key role in the unique characteristics of humans, including brain development.
In this study, researchers replaced the natural version of HARE5 in mice with the human version of this fragment. The result? These modified mice developed a cerebral cortex that was 6.5% larger compared to normal mice. This change, although modest in appearance, is enormous on a biological level, as the cortex is the region of the brain associated with higher functions such as thinking, memory, and decision-making.
How Does This Fragment Work?
The HARE5 fragment acts as a true genetic switch. It controls the expression of a gene called Fzd8, which plays an essential role in the growth and proliferation of nerve cells. More specifically, this fragment stimulates neural stem cells, called radial glia, which are the origin of neurons and other brain cells.
In mice carrying the human fragment, radial glia divide more, producing more neurons, which leads to a larger cortex. In other words, this small segment of human DNA “pushes” the brain to grow by promoting the multiplication of brain cells during development.
A Fragment, Four Key Mutations
To understand why the human version of HARE5 is so powerful, researchers analyzed its differences with the chimpanzee version. They identified four specific mutations in the human fragment, each contributing to strengthening the proliferation of cells. These mutations seem to optimize the function of this genetic regulator, amplifying its effect on brain development.
Toward a More Complex Brain
To further their research, the scientists used miniature models of human brains called organoids. These 3D structures cultivated in the laboratory allow for the study of brain development in a controlled environment. Organoids with the human version of HARE5 showed increased production of radial glial cells, confirming the impact of this fragment on brain growth.
the study reveals that HARE5 influences a key signaling pathway that regulates the division of neural stem cells, reinforcing its role as a driver in the expansion and complexification of the human brain.
A Piece of the Evolutionary Puzzle
Despite these advances, researchers clarify that this fragment is just one piece among thousands in the human genome. In fact, approximately 3,000 other human accelerated regions could also contribute to shaping our unique brain. Understanding how these different elements interact remains a major challenge for science.
Implications for Evolution and Health
Beyond evolution, this research could have important repercussions in neuroscience and medicine. Better understanding the mechanisms that control brain growth could help develop treatments for brain developmental disorders or neurodegenerative diseases.
