Published online 7 August 2008 | Nature | doi:10.1038/news.2008.1026

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Full nuclear sequence, offering clues about our relatives' demise, expected within months.

The first complete genome of a Neanderthal — specifically, the mitochondrial DNA found in a 38,000-year-old bone — has been sequenced.

The highly accurate sequence contains clues that our relatives lived in small, isolated populations, and probably did not interbreed with their human neighbours. “This is the first ‘finished’ genome sequence of an extinct human relative,” says the study’s lead scientist, Ed Green, of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

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Analysis of the DNA, taken from a bone fragment from the Vindija Cave in Croatia, puts the date of our last common ancestor at around 660,000 years ago, give or take 140,000 years. This is broadly in line with other estimates based on archaeology.

The research, published in Cell1, is a taster for the unveiling later this year of the complete Neanderthal nuclear genome sequence — which many hope will reveal the key genetic changes that propelled the evolution of human behaviour.

Mystery demise

Neanderthals lived across Europe and western Asia from a few hundred thousand years ago to around 30,000 years ago. Although a great deal is known about their physiology and social practices from archaeological and fossil evidence, the reason for their demise remains a mystery.

To date, there have been more than a dozen sequences of Neanderthal mitochondrial DNA published. “But for the first time, we've built a sequence from ancient DNA that is essentially without error,” says Green.

“Contamination has been a constant dark cloud hanging over the field of ancient DNA sequencing. It has tainted our work,” he says. “People have been too busy evaluating the accuracy of the Neanderthal sequences to really think about what these sequences actually mean if they are real.”

Two years ago, Green’s colleague Svante Pääbo began his project to map the entire Neanderthal genome, setting out to probe more than 60 museum specimens for traces of DNA. In an effort to eliminate contamination, the team have been generating DNA libraries in the same clean room where they do the DNA fossil extraction.

The scientists sequenced the Neanderthal mitochondrial genome 35 times, giving them enough data to compare it with the human genome and reliably identify which differences were caused by evolution, and which by sample degradation. The result is a genome sequence which was hailed as “extremely rigorous”, by Edwin Rubin, director of the Joint Genome Institute in Walnut Creek, California.

“The near complete absence of human contamination is enormously encouraging and bodes well for the Neanderthal nuclear genome sequences that have been generated from this sample,” says Rubin.

Genetic clues

The team found that of the 13 proteins encoded in the Neanderthal mitochondrial DNA, one in particular had experienced a significant number of amino acid changes in humans, since our separation from Neanderthals.

However, these changes did not have a significant effect on the functional domain of subunit 2 of cytochrome c oxidase (COX2), part of the mitochondrial electron transport chain.

Some scientists hope that genetic clues about why human rose to prominence and Neanderthals died out will be revealed in a few months, with the unveiling of the complete nuclear genome sequence. “We are on course to publish a complete one-fold coverage by later this year,” says Green.

But others are not convinced. “Whatever it was that sparked the emergence of human behaviour 30,000–40,000 years ago, I’m convinced it was not genetic,” says Erik Trinkaus a palaeontologist at Washington University in St Louis, Missouri.

“The genome sequence data may tell us something about the selection of a couple of proteins, but it tells us nothing about language or social behaviour,” says Trinkaus.