A 38,000-year old bone has yielded the world’s first complete Neanderthal mitochondrial genome sequence, offering a tantalising glimpse at the genetic changes that separate humans from Neanderthals, which split some 600 millennia ago.

The mitochondrion – a structure often dubbed the cell’s powerhouse – contains a mere 16,565 DNA letters that code for 13 proteins, whereas the nucleus holds more than 3 billion letters that produce more than 20,000 proteins. If DNA were to the size of a standard soccer pitch, then mitochondrial DNA (mtDNA) would be equivalent to a small flowerbed.

For the time being therefore, the largely symbolic and technical breakthrough offers only limited insight into the evolution of humankind. “It’s kind of opening the window a crack,” says Tom Gilbert, an expert on ancient DNA at the University of Copenhagen, who was not involved in the sequencing project.

Yet the research, led by Richard Green and Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, will pave the way for the construction and analysis of the complete Neanderthal genome. A rough draft should be finished by the end of the year, Green told New Scientist.


No sex, please

This is not to say that such mtDNA sequences are of no use to scientists. Previous work on shorter stretches of Neanderthal mtDNA has dated their last common ancestor with humans to about 660,000 years ago, give or take 140,000 years.

We know also that humans and Neanderthals didn’t interbreed enough to leave a mark in either genome. The new, complete sequence firms up these conclusions.

The code also offers tantalising clues to Neanderthal life and human evolution.

When Green’s team compared the protein-making portion of Neanderthal mtDNA to that of other primates, they found a pattern of genetic differences suggesting that either Neanderthals were evolving rapidly or that they lived in small groups, which would reduce genetic mixing.

Green and Gilbert both favour the latter interpretation because Neanderthals lived as hunter-gatherers, a lifestyle unsuited for large groups.

Evolutionary clues

One particular gene hints at a potentially important change in human evolution.

The DNA code for COX2, a gene involved in making cellular energy, varies enough between Neanderthals and humans to change its encoded protein at four places. The differences might affect how active the protein is, though it’s equally likely that the mutations are a fluke of human evolution, Green says.

Moreover, other such substantive differences between human and Neanderthal genes and proteins should point the way to what makes humans unique from other primates. “The Neanderthal can let us know where to look for things that might be important in recent human evolution,” Green says.

Less glamorously, the newly minted mitochondrial genome offers important technical insights into constructing and verifying far larger ancient genomes.

DNA crumbles somewhat predictably over time, and efforts to rebuild samples that are thousands of years old can introduce errors. Based on the Neanderthal mtDNA sequence in which each letter was read 35 times on average, Green’s team can now predict and correct potential errors in other ancient DNA sequences.

Gilbert notes that Green’s team went to extraordinary feats to prove that the Neanderthal sequence was unsullied by the DNA of its human handlers. Such bona fides should carry over to the complete genome, he says.

“When they do get the genome we can rely on it – really, that what we’re getting is Neanderthal, not human.”

Journal reference: Cell (DOI: 10.1016/j.cell.2008.06.021)

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