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On the hunt for ancient DNA, Stanford researchers improve the odds

110427-N-YY9999-002On the surface, it's perfect Halloween fodder: Ancient Peruvian mummies, Bronze and Iron Age human teeth from Bulgaria and a thousands-of-years old hair sample from Denmark. In fact, one attendee of Stanford geneticist Carlos Bustamante's talk this morning at the annual conference of the American Society of Human Genetics in Boston quipped that his introduction sounded like "the start of a joke."

But really old human DNA (we're talking thousands of years) holds amazing secrets about our distant past. What did we look like? Where did our ancestors come from? What diseases may we have had? Unfortunately, it's much more difficult than it seems to unlock these mysteries.

Stanford postdoctoral scholar Meredith Carpenter, PhD, explained the problem in an e-mail to me yesterday:

From Neandertals to mammoths to Otzi the Iceman, discoveries in ancient DNA sequencing have been making headlines.  But what you might not realize is that most of the ancient genomes sequenced to date have come from exceptionally well-preserved specimens – Otzi, for example, was literally frozen in ice for 5000 years.

Ancient DNA specimens from temperate environments, in contrast, are much trickier to sequence because they contain high levels of environmental contamination, primarily derived from bacteria and other microbes inhabiting the ancient bone. This contamination often makes it too expensive to sequence the tiny amounts of endogenous DNA (which degrades over the years due to exposure to the elements) remaining in a sample.

Now, Carpenter and Bustamante, PhD, and their colleagues have hit upon a way to enrich, or increase the proportion of ancient human DNA in an environmental sample from about 1.2 percent to nearly 60 percent--rendering it vastly easier to sequence and analyze. They do so by exposing the sample to a genome-wide panel of human-specific RNA molecules to which the degraded DNA in the sample can bind. The effect is somewhat like stirring a pile of iron-rich dirt with a powerful magnet to isolate the metal from the soil.

This isn't Bustamante's first foray into the secrets of ancient DNA. Last year he published very interesting results showing that the ancestors of the famous Iceman likely came not from mainland Italy, as previously thought, but instead from the islands of Corsica or Sardinia. This new technique should enable researchers to learn even more about our ancestors, including those oh-so-intriguing mummies.

According to Carpenter:

We hope that this new method will enable ancient DNA researchers to more cheaply sequence a larger number of specimens, providing broader insight into historical populations rather than just a few well-preserved individuals.

The research is published online today in the American Journal of Human Genetics. If you're interested in following tweets from the conference, which goes through tomorrow, you can do so by following hashtag #ASHG2013.

Previously: Iceman's origins discovered at Stanford, Stanford study investigates our most-recent common ancestors  and Recent shared ancestry between Southern Europe and North Africa identified by Stanford researchers.
Photo by Official US Navy Imagery

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