Runners-up: Svante Pääbo
Geneticist at the max planck institute for evolutionary anthropology
The genomes of humans and our closest living relatives, the chimpanzees, differ by just 1.23 percent. The difference between humans and our extinct cousins, the Neanderthals, is far smaller still: perhaps a tenth of that. Yet somewhere in that tiny gap lie the clues to what has been called "the great detective story of how we became what we are." Svante Pääbo, director of evolutionary genetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, is one of the most masterful sleuths tracking down those clues. Recently he set out to sequence the complete Neanderthal genome within two years, in preparation for a side-by-side comparison with our own.
Pääbo did not begin his career with the mysteries of human evolution in mind. He was deep into medical school in his native Sweden when, in 1980, he interrupted those studies to pursue a Ph.D. in molecular genetics. The timing was fortunate; the early 1980s were a boom period for the field, thanks to a newfound ability to cut, paste, and sequence DNA. Soon after, a technology called PCR would enable scientists to pick out and amplify desired DNA while ignoring rogue elements, such as fungal and bacterial DNA.
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Courtesy of Bela Dornon, MPI-EVA |
Ancient DNA is no picnic to work with. Bones rot, and the DNA in their marrow breaks down. Contamination from bacteria, fungi, and people—including well-meaning scientists who have touched the bones—is an ever-present problem. Recently, Pääbo's team had to probe some 60 different Neanderthal museum specimens to find just two containing viable material. He estimates that only 6 percent of the genetic material his team extracts from bones turns out to be Neanderthal DNA. A meticulous worker, Pääbo has been uniquely successful at producing clean results in the face of these odds.
In 1996, while a professor at the University of Munich, he and graduate student Matthias Krings recovered mitochondrial DNA from a 40,000-year-old piece of Neanderthal arm bone. An analysis of its sequence provided strong evidence that Neanderthals lie on a separate branch of the human family tree and are not our direct ancestors. It showed their evolutionary line splitting off from our own a little over 550,000 years ago, before modern humans emerged and before key changes in human brain evolution.
With new technology—developed by 454 Life Sciences Corporation of Branford, Connecticut—that vastly increases the number of short DNA segments that can be sequenced in a day, Pääbo can now go further. "Even a few years ago, I didn't imagine it would be possible to sequence the whole Neanderthal genome," he says. "This process is so cheap and efficient, it's a match made in heaven."
With the sequencing results in hand, Pääbo can make headway on exciting questions of evolution and identity. He has spent the past few years comparing chimp genes with our own, trying to reconstruct the crucial mutations responsible for our differences. In 2002 he reported that a gene known as FOXP2, which plays a role in language acquisition, produces a subtly different protein in humans than in chimps. Although the difference is small—just two amino acids—it is most likely significant, since the alteration was strongly favored by natural selection starting less than 200,000 years ago, around the time when human language took a great leap forward.
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The challenge now is to prove that those results are meaningful. "We don't even know how gene expression changes on a day-to-day basis!" says glycobiologist Ajit Varki, who studies ape-human differences at the University of California at San Diego. "Somebody made a joke about it, but it's not really a joke: 'What was that human thinking before he died? What was that chimp thinking before he died?'" Even if a particular difference between the species is real, it does not necessarily explain our divergent cognitive abilities.
Since a rough draft of the chimp genome became available in 2005, much research has focused on human gene sequences that are missing in apes. One way to discern their function: Breed chimps that carry a uniquely human stretch of DNA and see what happens to their brains. But chimps are so similar to us that this type of experiment is considered unethical. "The dilemma, when one is interested in human-specific traits, is that there's really no animal model you can use," Pääbo says. "It's almost getting a little boring to find more genes that have been selected for, without having the connection to what they do."
So Pääbo recently began a project to breed mice laced with human-specific genes. "One could imagine, say, if you introduced genes involved with brain growth during development, that you might actually see a bigger brain or a differently structured brain," he explains. "Or you could imagine introducing genes that have to do with speech and language and seeing a change there—some motor control of the thorax." The first of these humanized mice are now being born in Germany. "It's the next big step in understanding human evolution," Pääbo says. "It's kind of futuristic."
Read about Pääbo's—and science's—first run-in with Neanderthal DNA.
After Pääbo's discovery of intact Neanderthal DNA, DISCOVER writer Anne Casselman asks, will we ever clone a caveman?
View the Web site of 454 Life Sciences, the company taking on the Neanderthal genome with Pääbo.
