HARE5 Identified As Gene Regulator For Brain Size: Study

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Scientists are figuring out exactly why human have larger brains

A new study from Duke University Medical School researchers highlights the discovery of the gene regulatory pathway that controls the development of human brain size. The research was published last week in Current Biology, and scientists say the development of this gene regulatory pathway is one major factor that sets humans apart from genetic relatives in the primate world.

More on the gene regulator for brain size research

Human brains are truly unique in the animal world, even when compared to other primates like chimpanzees. Human brains are around twice as large and weigh three times more than other primate brains, and are significantly more complex and interconnected as well. Scientists believe these neurological differences enabled humans to evolve the higher brain function that other primates do not have.

However, research into exactly what genetic changes allowed humans to surpass other primates in the brain is just getting under way. The Duke researchers chose brain size to investigate as it seemed like an obvious starting point.

Using databases built by other researchers, the scientists referenced areas of human DNA that had developed differences from chimp DNA with areas of DNA they thought might be involved in gene regulation. Regulator genes are special genes that control how other genes express themselves, and the Duke team was pretty sure some gene regulators might be stimulating greater brain development in human embryos than in chimps.

They eventually narrowed their focus called HARE5 (short for human-accelerated regulatory enhancer), which testing indicated had something to do with brain development. They suspected that the enhancer, which is found close to a molecular pathway important in brain development, might have changed in a way that influenced brain size in humans.

Statement from Duke researchers

“We discovered that the human DNA sequence, which only had 16 changes in it compared to the chimp sequence, was being expressed differently in mice,” said study author Debra Silver, an assistant professor of molecular genetics and microbiology in the Duke University Medical School.

It turned out that inserting HARE5 into mouse DNA allowed the production of more neural stem cells (the precursors of brain cells) in mouse embryos.

“The human DNA was really able to accelerate the way the stem cells divide,” Silver commented. “And as a result, the mice were able to produce more neurons.”

“HARE5 seems to promote the ability to create more neurons and increase brain size, which allows human brain development to take advantage of that,” she noted.

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