One of the most intriguing mysteries of biology is why humans are the only species with a brain smart enough to ponder their own existence.
Researchers at the University of California at Santa Cruz believe they have discovered a possible answer: a gene that has undergone powerful mutational changes in the last 5 million years that may partly account for the accelerated evolution of the human brain.
Reporting Wednesday in the online version of the British medical journal Nature, the scientists said they do not know exactly what the gene does but that it is active at a key time and place in embryonic development when the brain is growing at its fastest pace.
"The properties of this gene are that it's turned on at about week seven of embryonic development in the same cells that help build the cerebral cortex," said David Haussler, director of the university's Center for Biomolecular Science and Engineering and a Howard Hughes Medical Institute investigator.
"And then it's turned off at about week 19 when the process is finished. It suggests that the gene is probably involved in this process of building the cerebral cortex because it's turned on in the right place at the right time and turned off in the right place at the right time."
Bruce Lahn, whose University of Chicago team reported earlier this year the discovery of two genes indicating the human brain is still evolving and perhaps becoming smarter, said the Nature report is a potentially important advance in uncovering the brain's genetic building blocks.
"Eventually all this information is going to come together and play a role in better human health and a better understanding of human evolution," he said.
Haussler's group found a gene called HAR1 that appears to exist in the brains of all animals. For most animals, from chickens to chimpanzees, the gene underwent little change for hundreds of millions of years, suggesting it performs a vital function.
But sometime in the last 5 to 7 million years, after the human lineage diverged from its last common ancestor with the chimpanzee, HAR1 began to change substantially. Today, approximately 10 percent of the human HAR1 gene is different than that of the chimpanzee, Haussler said, adding that the genetic changes may contribute to the human brain becoming three times larger than that of a chimp.
HAR1 belongs to a newly discovered type of gene made out of RNA instead of the usual DNA. RNA genes are made from DNA genes, but then they go on to act as genes in their own right. One of their jobs, it is thought, is to regulate other genes.
The HAR1 gene is active early in embryonic development when certain neurons produce a protein called reelin that guides the growth of brain cells and the formation of connections among them. The neurons orchestrate the layered structure of the human cerebral cortex, the brain's intelligence and command center. After this period of rapid development, HAR1 is turned off.
Scientists generally believe the complex human brain evolved over time because it provided a survival advantage to the vulnerable ancestors of humans.
"Why aren't there more species that have achieved the level of intellectual capability of humans? Why doesn't everybody want a big brain?" Haussler asked. "Well, the brain uses a lot of energy, about 20 percent of the energy in the body. It's definitely a costly organ to maintain from an energy perspective. I suppose if you're just out grazing on the grass all day, it's a waste of effort."
The tiny brain of the primitive sea squirt, for example, shrinks even smaller after birth, yet it gets along in its niche very well, pumping water in one hole and out another.
"Sea squirts have evolved a way of essentially getting rid of its brain," Haussler said. "It finds a rock, sits down on it, eats its own brain and becomes a kind of vegetable sitting on the rock, filter feeding.
"They have been very successful. They're happy. They don't need their brain," he said. Early humans, on the other hand, "got by by the skin of our teeth. It was our cunning that sculpted us as a species."
To help define the role of HAR1 in brain size, neuroscientist Pierre Vanderhaeghen of the University of Brussels, an author of the Nature paper, is developing a mouse strain that lacks the HAR1 gene. The purpose is to determine if the animals without the gene are born with smaller brains.
"If they delete the gene in a mouse and the mouse has a smaller brain, then one can argue that the changes in this gene might have contributed to a larger human brain," said the U. of C.'s Lahn.
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