Most male mammals wield a penis covered with spines made of keratin, the same material that forms fingernails, to sweep out competitors' sperm and irritate a female into ovulating. You can add humans' lack of penile spines to the list of ways we are misfits among primates, along with our absence of tails and fur. Even chimpanzees, our closest relatives, have penile spines. A new study suggests that this feature disappeared due to a chunk of DNA that went missing after our evolutionary divergence from chimps. The researchers have identified another DNA deletion that may have contributed to humans' bigger brains.
The question of what makes us distinctly human is hardly a new one, of course, but developmental genomicist Gill Bejerano and developmental geneticist David Kingsley, both of Stanford University in Palo Alto, California, decided to look at the issue from another angle. Maybe humans don't have an advantage over chimps genetically, as we often like to think we do—maybe we've actually lost something. Bejerano and Kingsley compared the chimp genome with the human genome, looking for DNA regions that chimps had but humans did not. And rather than looking at genes, as most research in the past has done, they examined DNA regions that don't code for genes but instead regulate how nearby genes are expressed.
They found 583 deletions in the human genome, and Bejerano says choosing which to study first was a tough decision. "Each region could be its own adventure," he says. They ended up choosing two: a deleted region near a gene for male hormone response and a region close to a gene involved in brain development. The Neandertal genome also lacks these regions, indicating that these deletions occurred more than half a million years ago.
To discover what these lost DNA regions did, the researchers cloned the chimp DNA into mice, engineering it so that places where the DNA was active would turn blue. The first stretch of DNA showed up in the penile spines of developing mouse embryos, as well as in spots on the face where sensory whiskers would develop, indicating that it caused these structures to develop in response to male hormones. The second piece of DNA appeared in an area of the brain called the subventricular zone, a hotbed of neuronal growth and expansion. Deleting this DNA may have removed a brake on neuronal growth, allowing humans' brains to expand, the researchers hypothesize this week in Nature.
"There's a tendency to think of genetic loss as a loss of things," says genomicist Maynard Olson of the University of Washington, Seattle, who was not involved in the research. But sometimes less is more, he says. In terms of evolution, he points out, deleting a stretch of DNA is a much faster process than evolving a whole new genetic system would be.
Human geneticist James Noonan of Yale University said that although the approach was "very clever," speculation about the physiological changes these two deletions caused and the role they played in shaping human evolution is premature.
With well over 500 deletions left to analyze, Bejerano and Kingsley expect many other researchers to jump in. "This study brings together genetics and development in a nice way; it's a pleasure to see these fields converge," says Bejerano. "Evolutionary stories play out best when you can wield both."