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:: By Carrie Golus, AB’91, AM’93

:: Photography by Dan Dry

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Investigations ::

Humans: a league of their own

Geneticist Bruce Lahn shows that the human brain evolved more rapidly than in other species.

Fundamentalist Christians and evolutionary biologists can agree on one point: human beings are unlike any other creature on Earth. While the Bible offers a spiritual explanation, biologists looking for the evolutionary equivalent have been puzzling over the matter since Darwin’s Origin of Species was published.

LINK: Bruce Lahn formulates how the human brain became big and complex.

Bruce Lahn formulates how the human brain became
big and complex.

Some scientists have assumed humans ended up with large, complex brains by the same plodding, accidental molecular processes that led to a bigger antler or a longer tusk. But Bruce Lahn, assistant professor of human genetics, and his Chicago team of researchers argue that just as humans are in their own league, so is human evolution. “We tend to think of our own species as categorically different—being on the top of the food chain,” Lahn says. “There is some justification for that.”

In the cover article of the December 29 Cell, Lahn and the lead authors—graduate student Eric Vallender and Steve Dorus, PhD’04—reported that the genes regulating brain development and function evolved much more rapidly in humans than in three other species. Human evolution was fast and furious, they claim, estimating there may have been thousands of mutations in thousands of genes over the brief span (in evolutionary terms) of 20 to 25 million years. Accomplishing so much in so little time suggests a selective process that is unique—but why? Human ancestors were quite social, and therefore, Lahn speculates, “social structure is perhaps the main force driving evolution of the human brain.”

To understand how human evolution differed, Lahn’s team studied 214 genes involved in brain development and function in humans, macaques, rats, and mice. For each gene, the researchers counted the number of changes in the DNA sequence that altered the protein produced. They then obtained the gene’s rate of evolution, scaling the number of changes to the evolutionary time needed to produce them. They found that brain-related genes evolved much more quickly in primates than in rodents, and that the changes sped up in the lineage leading to humans.

Of the 214 genes, the team also identified two dozen “outlier” genes that evolved especially swiftly in primates, several times faster than in rodents. Seventeen of these outliers are involved in controlling brain size and behavior—the areas most transformed during human evolution. Lahn and his colleagues now are focusing on these outlier genes, which may reveal more of the brain’s secrets.

The discovery about human evolution’s uniqueness was widely covered in the mainstream media, despite the predictable glut of 2004-in-review stories that might have squeezed it out. “It answered a few important questions about the genetic basis of how we evolved into the powerful species that we are. We all want to feel special about ourselves, I guess,” Lahn jokes in explanation. While many scientists would be flattered by the attention, he can afford to be blasé—the Cell paper completed his 2004 media trifecta, not counting being named to Crain’s Chicago Business’s list of “40 under 40” (Lahn is 35).

The first media burst came in the spring, when Lahn and his team published two papers in Human Molecular Genetics identifying two genes implicated in the dramatic expansion of the human cerebral cortex: Microcephalin and ASPM. (Both genes are among the outliers named in the Cell paper.) The size of the cerebral cortex—the area responsible for abstract reasoning and planning—is one of the defining aspects of what Lahn calls “human-ness.”

The pressure of natural selection, the team reported, led to dramatic changes in Microcephalin and ASPM, which both control brain size during human development. Unlike previous studies of the brain that focused mainly on comparative anatomy and physiology, Lahn’s was among the first to single out particular genes.

Then in November came the sex story. While it’s well known that sexual competition among males occurs at the behavioral and psychological level, Lahn and his team announced in Nature Genetics that it also happens on the genetic level.

The background: in some species of primates semen remains liquid after ejaculation; in others it can become a solid plug in the vagina, which might block later partners’ semen. Lahn found that a protein controlling semen viscosity evolved more rapidly in primate species with promiscuous females (such as chimpanzees) than those with faithful females (such as gorillas). Human women fall somewhere in the middle: “nothing like as promiscuous as female chimps,” a London Times reporter observed, though “neither are they as faithful as the female gorilla.”

Lahn had studied primate sexuality in the past, arriving at Chicago in 1999, the year after he earned a PhD from MIT. There he led efforts to map the entire human Y chromosome, discovering genes that control aspects of male fertility. As a result of his Y-chromosome research, in 1999 he was named one of Technology Review magazine’s “TR100s,” an annual list of young innovators that a committee of Nobel laureates, CEOs, and fellow scientists expects to change the world. Lahn switched to human evolution at the University, sensing that the latter offered greater potential for breakthrough discoveries.

Since then he has demonstrated an “uncanny ability to predict a novel solution or outcome predicated upon one or more unproven assumptions,” says Conrad Gilliam, chair of human genetics. While the typical scientist would hesitate to venture so far into the unknown, Gilliam says, “this style seems to match Bruce’s intellect and personality. It keeps him constantly chasing the big ideas.”

But big ideas aren’t always readily accepted by the public. Just before Lahn’s Cell paper appeared, a Gallup poll found only a third of Americans believe evolution is a theory well-supported by evidence. Lahn, who grew up in China, is bemused by this aspect of American culture, even when hostile e-mails pour in, “usually after the publication of an evolution paper that gets lay media attention.” One correspondent suggested he didn’t look nearly old enough to have witnessed human evolution.

“He’s one of the young stars,” David Ledbetter, once his boss and now director of the medical-genetics division at Emory’s School of Medicine, told Crain’s. For his part, Lahn hopes his upcoming research will provide proof of evolution in process—perhaps even before he turns 40.