Human DNA Gives Mice Bigger Brains Than Chimp DNA

Silver lab, Duke University

What makes us human is one of the most intriguing questions in biology. While it’s easy to point out the physiological and cognitive differences that separate us from our closest ape relatives, these are only the tip of the iceberg. What scientists are itching to divulge is which bits of DNA are responsible for our unique characteristics—what gave us the evolutionary shove that resulted in our success? Scientists could be one step closer to finally teasing out the answer with the discovery of a DNA sequence that, when introduced into mice, made their brains 12% larger than those with the same stretch from chimps.

Fascinatingly, despite these striking differences, this sequence contains only subtle changes between humans and chimpanzees. Furthermore, it doesn’t code for a protein, but instead controls the activity of other genes. This finding could therefore provide us with some long sought-after insight into the genetic mechanisms that led to our superior brains. You can read up on the study in Current Biology.

There’s no question—our brains are pretty special. Take the neocortex, for example. This relatively new addition to our brain, which contains some 100 billion cells, is the hub of our higher mental functions, and it’s significantly smaller in other great ape species. Its expansion throughout human evolution underlies our distinct mental abilities, but its genetic basis has been elusive.

Although we may share some 95% of our DNA with chimpanzees, our genome contains unique segments, called human accelerated regions (HARs), which remained largely unaltered during mammalian evolution but then underwent rapid change after we diverged from chimps. While they don’t encode proteins, scientists suspect that these could be responsible for our uniquely human traits. In particular, studies have hinted that HAR sequences which increase expression of certain genes, so called human-accelerated regulatory enhancers (HAREs), are likely candidates, but none had been linked to a specific trait before.

To delve deeper, scientists from Duke University began comparing the genomes of humans and chimps with the hope of finding HAREs that are both different between the two species and predominantly expressed in the brain. Out of 106 candidates, one in particular —HARE5—stood out because of its close proximity to a gene called Frizzled 8, which is known to be involved in a pathway crucial for brain development.

The team then added either the human version or the chimp version, which differed by only 16 DNA letters, into mouse embryos, alongside a reporter gene which made tissue turn blue whenever the enhancer was switching a gene on. Not only did they find that Frizzled 8 is likely under the control of HARE5, but embryos with the human DNA snippet also became blue sooner and over a larger area than those with the chimp version. Furthermore, human HARE5 caused neuronal precursor cells to divide more, resulting in more brain cells and thus a marked—12%—difference in brain size when compared with chimp HARE5, and the region affected was the neocortex.

“What we found is a piece of the genetic basis for why we have a bigger brain,” study author Gregory Wray said in a statement. “This is probably only one piece—a little piece.”

[Via Duke University, Current Biology, Science and National Geographic]

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