Doubled gene means extra smarts

Change during human evolution could have led to bigger brains

MONTREAL — Bigger, better human brains may be the result of a double dose of a gene that helps brain cells move around.

At least twice in the past 3 million years, a gene called SRGAP2 has been duplicated within the human genome, says Megan Dennis of the University of Washington in Seattle. Dennis and her colleagues have now shown that extra copies of this gene may account for humans’ thicker brain cortex, the brain’s gray matter where thinking takes place. 

The team had previously discovered that SRGAP2 is one of 23 genes duplicated in humans but not in other primates. Dennis found that an ancient form of the gene, which is located on human chromosome 1, was partially duplicated on the same chromosome about 3.4 million years ago. That partial copy makes a shortened version of the SRGAP2 protein.

Then, about 2.4 million years ago, a copy of the partial copy was created and added to the short arm of chromosome 1, Dennis reported October 13 at the International Congress of Human Genetics.

But just having extra copies doesn’t mean the gene is evolutionarily important. So Dennis and her colleagues examined the duplicate genes in more than 150 people and found that the copy made 3.4 million years ago is missing in some people. But the younger version of the gene has become fixed in the human population, meaning that absolutely everyone has it. Millions of years may seem like a long time, but it is actually quite speedy for fixing duplicated genes, Dennis says. The rapid assimilation could indicate that the gene is important in human evolution.

Working with collaborators, the researchers have found that the shortened version of the SRGAP2 protein interferes with brain cells’ ability to make projections called filopodia, which the cells use to move around. Reducing the number of projections streamlines the cells so that they can migrate further in the brain, perhaps allowing humans to build extra cortex layers, the team proposes.

The study represents much more work than anyone has previously done to link a genetic difference between humans and chimps to higher brain function, says Carlos Bustamante, a geneticist at Stanford University.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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