Modern man meets Neanderthal

October 15, 2010

Well, they actually did it. And the whole world knows about it now, even if the news is tens of thousands of years old. It was, of course, a juicy story for the world’s media: Neanderthals mated with modern humans! But for Svante Pääbo, Department Director at the Max Planck Institute for Evolutionary Anthropology in Leipzig, this is not the most important aspect of his discovery.

A new generation of sequencing machines

The Leipzig team had sent their samples to the US-based manufacturer of the latest generation of high-throughput sequencing machines. However, the manufacturer did not have a clean room there. “We knew that that could be problematic, but we wanted to test the new machines before investing in them,” explains the Max Planck Director. And that is where the foreign DNA is likely to have contaminated the samples. “It was annoying, but in retrospect it was a good thing, as it meant that we discovered a problem that we had to solve. This is how progress is made in science – we can’t get perfect results right away.”

DNA clusters on the screen of a genome sequencer.

In the meantime, the sequencing machines are in Leipzig and each fragment of Neanderthal sequence is marked with a tag of four bases, clearly distinguishing it from contaminating human DNA, which is unmarked. And one improvement followed another. The new generation of high-throughput sequencing machines from the US company 454 Life Science was a technological quantum leap. It really put the reconstruction of the sequence of three billion base pairs within reach: “That was when I realized that we were going to make it,” says Svante Pääbo.

Also Adrian Briggs, one of Pääbo’s colleagues who recently completed a doctorate in the Leipzig laboratory, believes that the significance of this new generation of sequencing machines cannot be overestimated: “We had to sequence more than one billion fragments. That would have been absolutely impossible using the type of machine available in 2004.” According to Briggs’ calculations, “It would have taken one of those machines 10,000 years, or 10,000 machines one year, to do this – and at a cost of several hundred thousand dollars, it would have been impossible to finance.”

The difference between the old and new generation of these otherwise nondescript boxes is perhaps best illustrated by a look at the palm-sized plates that contain wells in which the DNA fragments are sequenced: on the old machines, there were 96 indentations per plate; in the 454 Life Science machine, there are 1.6 million. “This means that we can sequence more than a million DNA fragments per plate, compared to the 96 per plate with the older model,” says Briggs.

Thanks to an additional cash injection from the President’s Strategic Innovation fund, the researchers were able to afford this state-of-the-art sequencing technology. “It has to be said that people in the Max Planck Society recognized the potential and provided the necessary resources,” says Pääbo.

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