The relationship between humans and chimpanzees, thought to be pretty close in evolutionary terms, now comes down to a number: 510. Those are the genetic elements, in key areas of the genome, that differ between the two species. Surprisingly they aren't 510 pieces of DNA that we have and chimps don't. It's actually the other way around.
But our loss, paradoxically, is also our gain. The absence of one piece may have led to a feature that anthropologists have been struggling to explain for centuries—our big, complicated, non-chimplike brain.
The removal of another piece is linked to a different body part that has also received a great deal of attention. It could explain anatomical differences between the human penis and chimp genitals, changes that may contribute to human mating and pair-bonding, behaviors that are decidedly different than in other primates.
The research, published this year in the journal Nature, is part of a recent spate of explorations into molecules and cells that is moving anthropology—the study of human evolution—beyond bones and stones and into new areas of biology.
"It's an exciting development," says Arnold R. Kriegstein, director of the stem-cell-research center at the University of California at San Francisco. "Most mutations lead to a loss of function, but this one may have produced an increase." He co-wrote an article, in the July 8 issue of Cell, that links a population explosion of particular brain cells to the large human neocortex, a process that could have evolved from other mammals. Another article from this summer, published online on July 25 in Proceedings of the National Academy of Sciences, tracks changes in chimp and human brains over their life spans, showing that the bigger human brains shrink in ways not seen in our primate relatives.
"These kinds of studies are taking on a greater role in anthropology," says Chet C. Sherwood, co-author of that work and an associate professor of anthropology at George Washington University. "We're using large-scale, powerful methods to discover where we came from and why we are the way we are."
At the same time, Mr. Sherwood cautions that "there is not just one mechanism for this. The underlying genetics are very complex." As Nina G. Jablonski, head of the anthropology department at Pennsylvania State University, puts it, "This is no 'gimme.'"
The identification of the 510 pieces of missing DNA, and the connection to the particular anatomical parts highlighted in the Nature paper, was made by Philip L. Reno, an assistant professor of anthropology at Penn State, and Alex A. Pollen, a graduate student at Stanford University. (Both were at Stanford at the time the work began, in labs headed by the biologists David M. Kingsley and Gill Bejerano.) "This all became possible because we have full sequences, full genomes now," says Mr. Reno. "It's the first time we've had sequences from several mammals in our lineage for comparison. That's really powerful," says Mr. Pollen.
Brains Without Brakes
Essentially, the researchers lined up DNA from humans, chimps, macaque monkeys, and mice. Mice and monkeys went their separate ways 60 million years ago, so any DNA similarities—and most of the DNA was similar—showed the scientists that most of the genomes had been extraordinarily stable for all that time.
When they focused on these stable regions in chimps and humans, however, the researchers found a surprise. There were 510 elements from the chimp genome that were gone in humans. "They just were not there. They had been deleted," says Mr. Reno. And since humans are rather obviously not chimps, it meant those deletions had some important functions. "The trick was to figure out what they were," says Mr. Reno.
The deletions were not genes, the DNA elements that hold the molecular code for proteins that build or maintain body parts. They were, in fact, noncoding regions. But that doesn't mean they were inert. Such regions, in fact, control genes, turning them off, on, or cranking up their volume to produce more proteins. So losing a control region could have a big genetic effect, even if the gene was still there.
Mr. Pollen began looking for genes, near these deletions, that could affect brain size. The average human brain is about 1,400 cubic centimeters, while a chimp brain is about 400. "I began searching for genes that normally suppress growth because losing that suppression might release the brakes on cell division and lead to brain expansion," he says. One deleted control region turned out to be sitting very close to a gene called a tumor suppressor. Tumors are unbridled lumps of growing, dividing cells; the suppressor gene stops them. But in the womb, the gene helps to "prune" neurons in the fetal brain, sculpting and shaping the nascent organ.
The missing control region next to it was a volume control. "This seems like evolution going in with a very fine needle," says Mr. Pollen. "Removing the control affects a period, early on, when the brain could grow." The brakes, in humans, are off. "But it leaves the gene itself intact, able to fight cancer later on."
The brakes were also off in Neanderthals, our closest relatives in the genus Homo. Researchers announced a complete Neanderthal genome in 2010, extracting and sequencing DNA from the thigh bones of three Neanderthals. Mr. Pollen had already identified the missing control region in humans, but if the region were present in big-brained Neanderthals, it would knock a large hole in his theory.
"It was a very exciting moment in the lab," he recalls. "We clustered around my computer and loaded up the genome browser. And we saw this bullet hole in the Neanderthal sequence, at the same spot where the control region was deleted in humans!" Two big-brained animals were missing the DNA element; their small-brained relative had it.
Smoothing the Way
Mr. Reno, while this was going on, was pursuing sex. Specifically, he was approaching human sexual anatomy in the same way that Mr. Pollen had investigated brain anatomy: trying to see if a deletion could explain a notable chimp-human change. Chimp penises are studded with small, hard spines. It's one reason, anthropologists have speculated, that chimp matings are very short and not terribly sweet. And those spines are generated, in the fetus, by a gene that releases the hormone androgen.
But not if its volume control is deleted, and that's just what the genome comparison showed: Gone in humans. And Mr. Reno added more evidence. He took the chimp control DNA and linked it to a gene that turns cells blue. That package was inserted in mice embryos. As they grew, the fetal mice began to show blue cells in their genitals. The volume control worked.
What did the deletion mean for humans? "I think the evolution of pair bonding and monogamy is what's going on," Mr. Reno says. Losing the spines meant longer acts of copulation and, basically, a better chance to get to know each other. Attachments formed. Pairs stuck around—a good thing for their offspring, whose bigger brains needed more care and feeding. It turns out that large brains need a huge amount of calories to function.
And that's the value of these studies about the evolution of development, or "evo devo," says Ms. Jablonski, of Penn State. Theories about brain enlargement, or the origins of monogamy, have been bandied about for years. This research points to specific genetic targets that, affected by evolution and natural selection, might tip a creature's anatomy or behavior in a human direction. But so many genes affect development, she notes, that "that this is not the pathway to instant enlightenment." Mr. Pollen's deletion, for instance, might account for 5 percent of brain growth, or 15 percent, or 50.
Nonetheless, "I can say that, without a doubt, the evo-devo approach is being enthusiastically embraced by biological anthropology, and people utilizing the approach are eagerly sought," Ms. Jablonski says. She would know. Her department hired Mr. Reno in January.
