How much can a single gene do?(Image: Dorling Kindersley/Getty Images

When it comes to brain development, slow and steady wins the race. A single ancestral human gene that made two copies of itself may have helped the evolution of our large brains 2.5 million years ago, as our ancestors were diverging from australopithecines.

Paradoxically, it seems the effect of the extra copies was to slow down individual brain development. This allowed time for neurons to develop more and better connections with one another.

Gene duplications are rare in human history: only about 30 genes have copied themselves since we split from chimps 6 million years ago. Few have been studied, but those that have encode genes that are very exciting, says human geneticist Evan Eichler of the University of Washington in Seattle. Many are involved in brain development.

Photograph of a photograph

Eichler and Franck Polleux of the Scripps Institute in La Jolla, California, chose to look at a duplicated gene called SRGAP2. It helps drive development of the neocortex, which controls higher-order brain functions such as language and conscious thought. Humans with mutations in this gene are prone to epileptic seizures, as are mice that have been engineered to lack it.


Eichler’s group discovered that SRGAP2 duplicated itself 3.5 million years ago, well after humans and chimps diverged. One million years later, this “daughter” of the original gene underwent its own duplication and created a “granddaughter” copy. All three coexist in modern humans.

But just like a photograph of a photograph, as the duplications took place, each copy decreased in quality. The daughter and granddaughter genes were shorter than the original and weren’t able to help the brain mature the way the original gene does.

In fact, they did just the opposite: when Polleux and colleagues put human copies of the daughter and granddaughter genes into mice, the proteins they made bound to the original SRGAP2 and hindered its ability to do its job.

The effect of this genetic sabotage, however, was that the brain had more time to develop. Although the mouse’s brain itself didn’t grow larger, the neurons in the neocortex changed to look like human brain cells, growing thick spines to exchange information with other cells. The neurons also formed 50 to 60 per cent more of these spines than normal mouse neurons do, which would likely increase the brain’s processing power.

Smarter mice?

Although Polleux and his colleagues have not yet figured out whether the mice were smarter, he says those experiments are in the works. They also plan to put the human genes into a much closer human relative, a marmoset, and see if its behaviour is altered.

The timing of the second duplication 2.5 million years ago, the researchers point out, coincides with when our genus, Homo, began separating from the now-extinct Australopithecus.

We know that the cognitive abilities of Homo must have increased tremendously to enable our ancestors to develop complex social structures and tools that australopithecines didn’t have. The rare double gene duplication may have been instrumental in this.

What’s interesting about the duplication, Eichler says, is that it would have changed brain development immediately and dramatically. Human ancestors with two, three, or even more copies of SRGAP2 – and consequently stark differences in their cognitive abilities – could have been running around together at one point. “That’s fun to think about,” he says.

Journal references: Cell, DOI: 10.1016/j.cell.2012.03.033 and 10.1016/j.cell.2012.03.034

This article was first posted under the headline “One gene helped human brains become complex”