Friday, November 27, 2009

Health

The Human Factor

By Nancy Shute
Posted 1/12/03
Page 2 of 3

Wilson's lab was the first to show that DNA from living humans could be used to trace the origin of modern humans back to Africa. It was also one of the first in the world to use PCR, a chemical process that made it simple to copy DNA a billion times over, turning a mere trace into enough to study. Paabo had not been able to analyze the mummy genes, but with PCR, he believed, ancient DNA could open a direct window into the past--looking tens or even hundreds of thousands of years back.

With PCR, Paabo was able to duplicate DNA from extinct animals like the quagga, a type of zebra, and the moa, a flightless bird, swiftly answering long-standing questions about their relationship to living animals. Other extinct creatures followed, including mammoths, ground sloths, and cave bears. With Michael Hofreiter and other graduate students, he has also extracted DNA from the feces of ancient animals and humans, revealing much about their diet, behavior, and environment.

But in coaxing DNA from 40,000-year-old Neanderthal bones, Paabo may have pushed ancient DNA as far as it can go. Old DNA is hard to find; its nucleotides degrade when exposed to water, oxygen, and heat. "I've looked at something like 270 samples," says David Serre, a graduate student who spends long hours testing bits of Neanderthal bone cadged from museums and universities. "Only 20 of them still contain DNA." Worse, modern human DNA is on everything we touch. It can easily mislead researchers. Spectacular claims--such as one that Chinese researchers had extricated DNA from a dinosaur egg--were proved false when closer analysis revealed that the molecules were merely modern contamination. "It's rather embarrassing," Paabo says, rolling his eyes.

A relative. With ancient DNA giving just narrow glimpses into the past, Paabo is turning to what could grant a wide-angle view--the genes of the great apes. Chimpanzees, our closest cousins, share 98.7 percent of their DNA with humans. The trick is to find what in that 1.3 percent difference accounts for the things that make Homo sapiens special--language, reasoning, MTV. The chimp genome is being sequenced in labs around the world. When it's done, in 18 months or so, it should be a powerful tool for understanding how the species diverged.

For now, Paabo is fishing for another kind of difference. He is comparing patterns of gene activity in ape and human tissues to learn where genes are switched on and off. "We find so many differences, which is surprising," says Wolfgang Enard, a graduate student. "They are particularly pronounced in the human brain." The group has also found that methylation, a process that can adjust gene activity, is more prevalent in the human brain, suggesting it is a more finely tuned instrument. And last year, Enard found a key difference in the human and ape versions of Foxp2, a gene that was recently found to be essential for human speech. Mathematical analysis suggests that the human variation cropped up about 200,000 years ago, which could be about the time speech emerged.

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