WEB EXCLUSIVE

The Gene That Made Us Human

Scientists decode a critical gene that may have led to the evolution of our big brains

By Zach Zorich|Thursday, March 04, 2004

Scientists have long suspected that humans evolved large brains because our hominid ancestors had to outwit and elude predators, learn to use fire, and develop complex social structures. The smart hominids survived, while the stupid ones were more likely to get eaten or freeze to death. Over millions of years, the result of this game of survival of the fittest was the appearance of big-brained, peculiarly intelligent modern humans. Now Bruce Lahn, a biomedical researcher at the University of Chicago, has found the first clear indication of the genetic changes that led to the rapid expansion of our brain.

Lahn and his colleagues looked at the abnormal spindle-like microcephaly associated (ASPM) gene, which scientists had previously identified as a key player in brain development. He grew intrigued by ASPM after other researchers discovered that serious defects in the gene cause microcephaly—a drastic reduction in the size of the brain’s cerebral cortex, the region responsible for such higher brain functions as abstract thought and planning. Lahn wondered: Could changes in this gene, favored by the pressures of natural selection, have directed the development of the big, modern human brain?

To find out, Lahn compared the sequence of the human ASPM gene with the equivalent gene sequences of various primates—including chimpanzees, gorillas, and gibbons—and with the sequences of nonprimate species such as mice, cows, and dogs. He isolated genetic mutations that altered the structure of the ASPM protein and thus could have affected brain size, while weeding out the random mutations that had no structural effect and hence would have been unaffected by evolutionary pressures. Lahn found that the ASPM gene in humans has undergone 15 important mutations since we last shared a common ancestor with chimpanzees, about 5 million years ago. Significantly, compared with the other animals studied, humans have experienced the fastest overall rate of change in the gene since our evolutionary line parted ways with chimpanzees and other primates. Evidently, ASPM responded to natural selection, and the resulting changes contributed to our large brains.

How exactly the ASPM gene produced these changes is not yet entirely clear. It seems to control how many times cells in the cerebral cortex can divide, which controls how much space there is for neurons. A variant of the gene that allowed additional cell divisions, Lahn surmises, gave some hominids the additional neural infrastructure that eventually let them develop abstract reasoning and language skills. The exact environmental pressures that pushed humans toward higher intelligence also remain a matter of speculation. “Humans are very social, and coming down from the trees to live on the African plains could have triggered a situation where higher cognitive abilities were highly favored,” Lahn says. The need for hominids to work cooperatively to find food and to combat the increased threat of large predators could have fostered the development of a larger brain capable of processing language and anticipating danger.

In future experiments, Lahn will insert the human ASPM gene into mice to see what affect it has on brain development. He hopes to reconstruct the detailed story of how the human brain grew and changed as the result of natural selection, thereby creating the thing that makes us each unique—the human mind.

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