Human DNA Code is Inserted into Mice to Enlarge Their Brains in a Study of Evolution

The human brain has expanded dramatically over the course of our evolution. But how did the human brain get so big? Now, scientists have taken a closer look and have found a genetic code in humans that can enlarge mouse brains.

Humans are actually equipped with tiny differences in a particular regulator of gene activity, called HARE5. When introduced into a mouse embryo, this code led to a 12 percent larger brain than in the embryos treated with the HARE5 sequence from chimpanzees.

"I think we've just scratched the surface, in terms of what we can gain from this sort of study," said Debra Silver, one of the researchers, in a news release. "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."

The researchers came to these findings after mining databases of genomic data from both humans and chimpanzees. They looked for enhancers expressed primarily in the brain tissue and early in development. Initially, they had 106 candidates. Six of them were near genes that are believed to be involved in brain development. These enhancers were labeled HARE 1 through HARE6.

The strongest candidate, in the end, was HARE5 for its chromosomal location near a gene called Frizzled 8, which is part of a well-known molecular pathway involved in brain development and disease. In mouse embryos, the human version of HARE5 was active earlier in development and more active in general than the chimpanzee version.

"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," said Silver.

The findings reveal a bit more about the genetic basis for why we have a bigger brain. This, in turn, shows a bit more about how complicated these changes must have been over the course of evolution.

Currently, the researchers hope to study the human HARE5 and chimp HARE5 mice into adulthood to see possible differences in brain structure and behavior.

The findings are published in the journal Current Biology.

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