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A small section of DNA that has rapidly evolved in humans could play a key role in the development and evolution of the human brain, according to research published online yesterday in the journal Nature. Although scientists don’t yet know exactly how the gene functions in the brain, they do know that the sequence is entirely unique to humans and is expressed in the cortex – which is responsible for complex thought – during a key stage of brain development.

“This is a very exciting finding,” says Bruce Lahn, a geneticist who studies brain evolution at the University of Chicago. “It brings us one step closer to the overall goal of understanding human brain evolution at the level of genes.”

Sometime in the last five to seven million years, when humans and chimpanzees split from each other on the evolutionary tree, our brains became three times bigger than those of our closest primate relatives. That impressive growth was largely due to expansion in the cerebral cortex, the outer layer of the brain responsible for reasoning and other types of complex thought. Since the sequences of the human and other animal genomes have become available for study, scientists have been scouring reams of DNA for genetic clues to our brains’ unique growth spurt – and to the biological changes that make us uniquely human.

In the new paper, researchers at the University of California, Santa Cruz compared the human genome to the genomes of chimps, dogs, rats, mice, and chickens, searching for genetic sequences that were highly conserved during evolution and therefore functionally important. They then looked for sequences within those conserved regions that had changed rapidly in humans, indicating that those changes were important for human’s unique evolution.

The researchers identified several rapidly evolving chunks of DNA, but the fastest piece by far was a small chain of DNA that’s part of a gene expressed in the hippocampus, which is involved in learning and memory. According to the findings, the sequence was very similar in chickens and chimps, with only two changes to the genetic code; but it had changed remarkably in human DNA, showing 18 genetic differences from the version in chimps.

“That really confirmed that this [sequence] is specific to the human lineage,” says David Haussler, a genomics expert at UCSC who led the work. “We also sequenced human DNA from different people around the world – everyone seems to have these same 18 variations.”

The researchers then discovered that the gene, known as HAR1F, has some even more enticing properties: it is expressed in a particular set of cells in the human brain between 9 and 19 weeks of gestation – when the cortex is undergoing a rapid period of development. “It’s essentially the initial phase of the development of the cortex, the thinking part of the brain,” says Haussler. “That’s the part of our brain that’s gotten so much bigger during the last few million years of evolution.”

Since scientists don’t yet know the function of the gene, it’s difficult to predict its role in brain development or human evolution. “Finding these rapidly evolving genes is a starting point to understanding human genetic evolution,” says Lahn, “but it doesn’t tell us how changes in the genetic sequence lead to changes in human biology.”

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Tagged: Biomedicine

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