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A Human Brain Gene Could Hold Clues On The Evolution Of Brain Capacity

olecular biology to characterize the gene, identify the tissues in which it is active, and begin the search to understand its function.

HAR1 is part of two overlapping genes. One of those genes, called HAR1F, is active in special nerve cells, called Cajal-Retzius neurons, that appear early in embryonic development and play a critical role in the formation of the layered structure of the human cerebral cortex. Cajal-Retzius neurons release a protein called reelin that guides the growth of neurons and the formation of connections among them. HAR1F is active at the same time as the reelin gene.

"We don't know what it does, and we don't know if it interacts with reelin. But the evidence is very suggestive that this gene is important in the development of the cerebral cortex, and that's exciting because the human cortex is three times as large as it was in our predecessors," Haussler said. "Something caused our brains to evolve to be much larger and have more functions than the brains of other mammals."

Pollard, as a postdoctoral researcher at UCSC, was part of the international team that performed the initial analysis of the chimpanzee genome. She and Haussler then devised a computational strategy for using the chimp genome and comparative genomics to identify regions of the human genome that had evolved rapidly.

"When we developed this computational method, we weren't sure what we would find. It was very rewarding to find that this region that came out at the top of our list is potentially relevant to human evolution in an interesting way," Pollard said.

Pollard's analysis showed that HAR1 is essentially the same in all mammals except humans. There were only two differences between the chicken and chimp genomes in HAR1's sequence of 118 bases (bases are subunits of DNA, the As, Cs, Ts, and Gs that spell out the genetic code). This similarity means the DNA sequence remained unchanged over hundreds of millions o
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