Discovering the secret of the DNA segment that makes the human brain different

Scientists at the University of California San Diego School of Medicine have discovered a small but powerful piece of DNA called HAR123 that may help explain why the human brain is so unique.

Finding the secret of the DNA segment that makes the human brain different. (Source: Science Daily)

Unlike genes, HAR123 acts as a “volume control” during brain development, controlling how brain cells form and the proportions between them. Notably, the human version of HAR123 works differently than the chimpanzee version, which may have given humans greater flexibility in thinking and learning.

HAR123 belongs to a group of “human accelerated regions” (HARs), which are stretches of the genome that have accumulated mutations at an unusual rate since humans diverged from chimpanzees about 5 million years ago. HARs are thought to play a key role in shaping unique human traits and have been linked to neurodevelopmental disorders such as autism.

The study found that HAR123 is not a gene but a “transcriptional enhancer”—a factor that controls which genes are activated, how much they are activated, and when they are activated during development. HAR123 promotes the formation of neural stem cells, which are precursors to the two main cell types in the brain: neurons and glia, and influences the ratio of these two cell types.

The results show that HAR123 contributes to the formation of a remarkable evolutionary trait of humans called “cognitive flexibility,” the ability to change and replace learned knowledge.

Experiments also demonstrated that the human version of HAR123 produced distinctly different molecular and cellular effects than the chimpanzee version in both cultured neural stem cells and progenitor cells.

Scientists say this discovery not only helps clarify the evolutionary origins of the human brain but also opens up new research directions on the molecular mechanisms behind neurodevelopmental disorders, including autism.

The study, published online in the journal Science Advances , was led by Professor Miles Wilkinson and Associate Professor Kun Tan (Department of Obstetrics, Gynecology and Reproductive Sciences, UCSD School of Medicine), with partial financial support from the US National Institutes of Health (NIH) and the biotechnology company 10x Genomics.

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