Human gene sequence leads to bigger mouse brain


The dark blue stains in these developing mice embryos show that the human DNA inserted into the rodents turns on sooner and is more widespread (right) than the chimp version of the same DNA, promoting a bigger brain.
Silver Lab, Duke University

Researchers at Duke University have attempted to describe how our brain grew significantly larger than our closest living relatives, the chimpanzee, if our genes are practically all the same.

The size of the human brain expanded in a dramatic manner during our evolution into Homo Sapiens, attributing to the development of abstract thinking and language, as well as complex problem solving in fields such as mathematics.

The human version of a DNA sequence called HARE5 turns on a gene important for brain development (gene activity is stained blue), and causes a mouse embryo to grow a 12 percent larger brain by the end of pregnancy than an embryo injected with the chimpanzee version of HARE5.
Silver lab, Duke University

The team at Duke have found that humans are equipped with slight differences in a regulator of gene activity, called HARE5, that when introduced into a mouse embryo, led to larger brain development than in the embryos treated with the HARE5 sequence from chimpanzees.

After adding the human HARE5 sequence to a group of mice embryos, and the chimp HARE5 sequence to another group of mice embryos, the researchers found that the neocortex, involved in higher-level function such as language and reasoning, was the region of the brain affected most (12% bigger in the human HARE5 mice than the chimp HARE5 mice).

The human HARE5 and the chimpanzee HARE5 gene sequences differ by only 16 letters in their genetic code, so any differences would seem insignificant. Nonetheless, the study demonstrated that in mice embryos, the human enhancer activates earlier in development and is more active in general than the chimpanzee enhancer.

"What we found is a piece of the genetic basis for why we have a bigger brain, " study co-author Gregory Wray of the Duke Center for Genomic and Computational Biology said. "It really shows in sharp relief just how complicated those changes must have been. This is probably only one piece - a little piece."

The team plan to follow the HARE5 human and HARE5 chimp mice into adulthood, and report any further differences in brain activity over their lifetime.

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