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by Michael Balter

In 1984, a team led by Allan Wilson of the University of California, Berkeley, made scientific history: It published the first partial sequences of ancient mitochondrial DNA (mtDNA), from a museum specimen of the quagga, a zebralike animal that had gone extinct almost exactly 100 years before. Thus was born the field of paleogenetics, which celebrates its 25th anniversary this year. Over that quarter of a century, ancient DNA studies have opened new doors to our understanding of human evolution, tracked ancient diseases and the spread of farming, and unraveled the complex phylogenies of woolly mammoths and the bear family. But along with the triumphs have come setbacks and occasional disasters, as paleogeneticists have discovered to their chagrin how easily ancient DNA samples can become degraded and contaminated with modern DNA, giving rise to erroneous and misleading conclusions.

At her opening talk to an ancient DNA meeting this week in Paris,* Eva-Maria Geigl of the Jacques Monod Institute in Paris toured this tumultuous history. Geigl, who organizes an international meeting of ancient DNA experts in Paris every 3 years, pointed out that the field had a “tormented youth.” Just 3 years after extracting mtDNA from the quagga, Wilson’s team discovered that some of its sequences had undergone chemical alteration after the animal died, complicating attempts to figure out how closely related the extinct animal was to living horses and zebras. And in 1994, the claims of a research team to have sequenced dinosaur DNA—later discovered to be human contamination—nearly led to the premature death of paleogenetics. “DNA damage and DNA contamination almost killed the field,” Geigl said.

geiglpicture2 Happily, paleogenetics survived these early setbacks, as ancient DNA leaders began insisting on more rigorous standards. Among them were aseptic methods of excavation, as shown at left, to be sure that researchers did not contaminate samples with their own DNA, as well as laboratory controls to minimize the amplification of modern DNA. As a result, Geigl says, paleogenetics was able to regain its credibility, as shown by the successful extraction of DNA from medieval plague bacteria, extinct cave bears, early samples of domesticated cattle, pigs, maize, and wheat, not to mention Neandertals, one of the field’s greatest triumphs. After the first complete sequencing of mtDNA, from two species of moa (extinct flightless birds) in 2001, it was only a matter of time before ancient DNA researchers would turn to completely sequencing both the mtDNA and nuclear DNA of Neandertals and begin to solve that extinct hominin’s genetic relationship with modern humans once and for all.

Nevertheless, as researchers carry out ever more ambitious and sophisticated ancient DNA projects, the problems that plagued the field in its early days could threaten it again, Geigl said. This is especially true for paleogenetics studies involving poorly preserved DNA samples, such as those of the first domesticated cattle and pigs in the Near East, and where dry conditions result in poor DNA preservation. Geigl pointed out that many reagents used in molecular biology labs are prepared using products such as gelatin and bovine serum albumin, which derive from cattle and pigs and so contain traces of cattle and pig DNA. In a study carried out by her lab, Geigl reported, 13% of 1170 “blank” control samples were contaminated with bovine and porcine DNA. Another source of contamination came to light during forensic investigations into the 15-year career of an alleged serial killer called “The Phantom of Heilbronn,” who supposedly left her DNA at dozens of crime scenes across Europe. It turned out, Geigl reminded the audience, that the DNA actually came from a woman who worked in a cotton swab factory and had contaminated the swabs—used to collect DNA samples—with her own genetic material.

The answer to these problems, Geigl concluded, lies in new and improved techniques to decontaminate DNA samples before they are amplified and sequenced, some of which her own research team is currently working on. If they work out, paleogenetics can be sure of many more birthdays to come.

*Ancient DNA: From mitochondrial to nuclear DNA, from the evolution of populations to the selection of characters—25 years of paleogenetics, Paris, France, 14-16 September.

 

Photo credit: Courtesy of Eva-Maria Geigl

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