Scientists pinpointed the genetic changes that cause human brains to grow larger than chimpanzees' brains and found they could use them to enlarge mice embryos' brains.

Humans exhibit small differences in HARE5, which is a specific regulator of gene activity. Mice that were introduced to human HARE5 grew brains that were 12 percent larger than those introduced to HARE5 sequenced from chimpanzees, Duke University reported.

"I think we've just scratched the surface, in terms of what we can gain from this sort of study," said Debra Silver, an assistant professor of molecular genetics and microbiology in the Duke University Medical School. "There are some other really compelling candidates that we found that may also lead us to a better understanding of the uniqueness of the human brain."

Genomes across all species contain thousands of short pieces of DNA, dubbed "enhancers," that control the activity of genes. Until the recent study no human-specific enhancers were known to directly influence brain anatomy.

To make their findings researchers scoured through databases of genomic data from both humans and chimpanzees, and pinpointed six that were most likely involved in human brain development; this group of enhancers was named  "human-accelerated regulatory enhancers" (HARE). The team believed HARE5 was the strongest candidate for playing a key role in human brain development because of its close proximity to the gene Frizzled 8, which is part of a molecular pathway linked to brain development and disease.

The scientists found human and chimpanzee HARE5 differed by only 16 letters in their genetic codes, but the human version was more active and kicked in earlier in development.

"What's really exciting about this was that the activity differences were detected at a critical time in brain development: when neural progenitor cells are proliferating and expanding in number, just prior to producing neurons," Silver said.

The mouse embryos with Frizzled8 under control of human HARE5 showed faster neuron proliferation chimp HARE5 mice, resulting in a greater number of neurons. The human HARE5 mice also showed differences in brain size that were visible to the naked eye.

The research team plans to follow the human HARE5 and chimp HARE5 mice throughout their adulthood in hopes of noticing differences in behavior and brain structure.

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

The findings were published in a recent edition of the journal Current Biology.