Two key brain-building genes, which underwent dramatic changes in the past that coincided with huge leaps in human intellectual development, are still undergoing rapid mutations, evolution's way of selecting for new beneficial traits, Bruce Lahn and his University of Chicago colleagues reported in Friday's issue of the journal Science.

The researchers found that not everyone has these genes, but that evolutionary pressures are causing them to increase in the population at an unprecedented rate. Lahn's group is also trying to determine just how smart these genes may have made humans.

'We're Not Played Out as a Species'

One of the mutated genes, called microcephalin, began its swift spread among human ancestors about 37,000 years ago, a period marked by a creative explosion in music, art, religious expression and tool-making.

The other gene, ASPM (abnormal spindle-like microcephaly-associated), arose only about 5,800 years ago, right around the time of writing and the first civilization in Mesopotamia, which dates to 7000 BC.

"People have this sense that as 21st century humans we've gotten as high as we're going to go,"' said Greg Wray, director of Duke University's center for evolutionary genomics. "But we're not played out as a species. We're still evolving and these studies are a pretty good example of that."

Just as major environmental changes in the past, such as dramatic shifts in the climate, food supply or geography, favored the selection of genetic traits that increased survival skills, the pressures on gene selection today come from an increasingly complex and technologically oriented society, said Lahn, a professor of human genetics and a Howard Hughes Medical Institute investigator.

"Our studies indicate that the trend that is the defining characteristic of human evolution -- the growth of brain size and complexity -- is likely still going on," he said.

"Meanwhile, our environment and the skills we need to survive in it are changing faster then we ever imagined," Lahn said. "I would expect the human brain, which has done well by us so far, will continue to adapt to those changes."

Evolutionary changes occur when a member of a species experiences a mutation in a gene that gives him a new skill, like running faster, seeing farther or thinking better. The genetic mutation increases his likelihood of survival and having more children, thereby allowing the new mutation to spread quickly through the population.

That's what happened to the microcephalin mutation, which now occurs in 70 percent of all people, and the ASPM gene mutation, which so far has spread to 30 percent of the world's people.

How a Brain Gets Wired

Other experts called the Chicago studies "stunning" but said that while the two genes appear to make people smarter by helping to engineer bigger brains, there are many more genes involved in brain building and human intelligence and cognition.

"It's very exciting but it's really just the beginning of a whole new phase of research," Wray said. "These aren't going to be the only genes and these aren't going to be the only changes. We don't even really know exactly what these changes mean, but it's a glimpse into the future of our understanding of how the human brain came to be and function the way it does."

Probing the genes of intelligence has been controversial in the past and is likely to be so now because of fears the knowledge could be misused to grade people's intelligence based on their genes.

But intelligence is a complex issue that is greatly influenced not only by the genes people inherit, but also by their early learning experiences.

Researchers have learned over the last two decades that genes and the environment work together -- genes provide for a range of possible outcomes and the environment determines which specific outcome is likely to occur.

Most of the brain, for instance, gets built after birth when learning experiences determine the way in which brain cells connect to each other. How a brain gets wired directly affects its computing power.

"There are genetic differences that make each of us unique," Wray said. "But there's no way for you to look at a single gene and say 'Ok, you've got this mutation, you're smarter than someone else.' Maybe at some point we will know that but not with these genes."

Natural Selection

Ever since the human line diverged from other primates between 6 million and 8 million years ago the human brain grew steadily bigger as a result of selective genetic mutations. Chimps, our closest primate relative, on the other hand, stayed pretty much the same.

Some 200,000 years ago, the anatomically modern human emerged with a brain three times the size of that of a chimp. As humans got smarter, Lahn said, selection pressure for smartness became intensified.

The microcephalin and ASPM genes played a big role in expanding the size of the brain. People born with defects in these genes develop brains that look normal but are only one-third the size of a full-grown human brain. As a result, their mental capacity is sharply reduced and they cannot live on their own.

"With a bigger brain you have more connections and more opportunity for things like language and symbolic representation, all the things that make us special as human beings," Wray said.

To show that brain evolution is an ongoing process, Lahn's team studied the genes of more than 1,000 people representing 59 ethnic populations worldwide. Their genes were compared to those of the chimpanzee to provide an historical marker as to what the genes looked like before they diverged.

Both the microcephalin and ASPM genes come in a number of different varieties. They all do the important job of building the brain but with slightly different variations that occur among specific population groups. At this point scientists are trying to precisely understand what extra benefits seem to be conferred by the variations.

The new variations in the microcephalin and ASPM genes occurred at a frequency far higher than that expected by chance, indicating that natural selection was driving their spread in the population.

The U of C researchers found that one variety of the ASPM gene identified as haplogroup D occurs more frequently in Europeans and surrounding populations, including North Africans, Middle Easterners and South Asians. It has a lower rate of occurrence in East Asians, New World Indians and sub-Saharan Africans. A specific variety of the microcephalin gene, also called haplogroup D, was most abundant in populations outside of sub-Saharan Africa.

"What we're seeing is that there is genetic variation in the human population that selection cares about," Wray said. "It means that evolution is still happening."