Human Brain Evolution Triggered By Duplicate Gene
May 4, 2012

Human Brain Evolution Triggered By Duplicate Gene

Brett Smith for

Scientists may have just found a ℠missing link´ in the form of a partial, duplicate gene that appears to be responsible for human brain development - the most distinguishing characteristic of our species.

The genetic variation occurred in man´s ape-like ancestor about two or three million years ago, according to a pair of studies published online in the journal Cell. A team led by researchers at the Scripps Research Institute found that a partial SRGAP2 gene duplicates interfere with the function of the original gene and allows maturing neurons to migrate farther and develop more connections.

"This appears to be a major example of a genomic innovation that contributed to human evolution," said Franck Polleux, a professor at The Scripps Research Institute.

The SRGAP2 gene was first singled out for study by researchers because it helps drive development of the neocortex, which controls higher-order brain functions.  Mutations in this gene have been found to cause certain brain disorders.

Another group of researchers led by Evan Eichler of the University of Washington discovered that SRGAP2 duplicated itself 3.5 million years ago, after humans and chimps diverged. One million years later, this partial copy, or “daughter,” of the original gene underwent its own duplication and created a "granddaughter" copy. Like a game of Telephone, each version of the gene underwent certain changes so that they resembled the original less and less with each successive copy.

"These evolutionarily recent gene duplications are so nearly identical to the original genes that they aren't detectable by traditional genome sequencing methods," said Polleux. "Only in the last five years have scientists developed methods to reliably map these hominid-specific duplications."

To test their theory, Polleux and his colleagues put human copies of the daughter and granddaughter SRGAP2 genes into mice. The proteins made by these human genes bound to the original SRGAP2 and hindered the gene´s ability to do its job.

Although the mouse didn´t develop a human brain, the neurons in the neocortex grew to look like human brain cells. The neurons also formed 50 to 60 percent more of these spines than normal mouse neurons, a sign of higher brain power.

This discovery means that changes in the SRGAP2 gene would have changed brain development both immediately and dramatically. Changes in behavior would be noticeable immediately, with the primates able to communication and collaborate much more effectively.

Scientists said they believe these findings extend far beyond simply satisfying the curiosity of evolutionary question.

"The finding that a duplicated gene can interact with the original copy also suggests a new way to think about how evolution occurs and might give us clues to human-specific developmental disorders such as autism and schizophrenia,” Polleux said.

Scientists will now look at the SRGAP2 genes with more scrutiny when investigating brain disorders including autism, epilepsy and schizophrenia.

Researchers involved in these studies said in future studies they plan to put the human genes into a much closer human relative, a marmoset, and see if its behavior is altered.