Welcome to the family (Image: Javier Trueba/MSF/Science Photo Library)

How closely are Neanderthals related to us?

They are so closely related that some researchers group them and us as a single species. “I would see them as a form of humans that are bit more different than humans are today, but not much,” says Svante Pääbo, a palaeogeneticist at the Max Planck Institute in Leipzig, Germany, whose team sequenced the Neanderthal genome.

The common ancestor of humans and Neanderthals lived in Africa around half a million years ago. After that, the ancestors of Neanderthals moved north and eventually made it to Europe and Asia. Our ancestors, meanwhile, stuck around Africa until about 100,000 years ago before eventually conquering the globe. Neanderthals died out around 28,000 years ago.


How did they sequence the Neanderthal genome?

Bone contains DNA that survives long after an animal dies. Over time, though, strands of DNA break up, and microbes with their own DNA invade the bone. Pääbo’s team found ways around both problems with 38,000 and 44,000-year-old bones recovered in Croatia: they used a DNA sequencing machine that rapidly decodes short strands and came up with ways to get rid of the microbial contamination.

They ended up with short stretches of DNA code that computers stitched into a more complete sequence. This process isn’t perfect: Pääbo’s team decoded about 5.3 billion letters of Neanderthal DNA, but much of this is duplicates, because – assuming it’s the same size as the human genome – the actual Neanderthal genome is only about 3 billion letters long. More than a third of the genome remains unsequenced. “It’s pretty darn good for something that’s 38,000 years old,” says Edward Green, a team member now at the University of California, Santa Cruz.

What did they find?

Any human whose ancestral group developed outside Africa has a little Neanderthal in them – between 1 and 4 per cent of their genome, Pääbo’s team estimates. In other words, humans and Neanderthals had sex and had hybrid offspring. A small amount of that genetic mingling survives in “non-Africans” today: Neanderthals didn’t live in Africa, which is why sub-Saharan African populations have no trace of Neanderthal DNA.

It’s impossible to know how often humans invited Neanderthals back to their cave (and vice versa), but the genome data offers some intriguing details.

“It must have been at least 45,000 years ago,” says David Reich, a geneticist at Harvard Medical School who was involved in the project. That’s because all non-Africans – be they from France, China or Papua New Guinea – share the same amount of Neanderthal DNA, suggesting that interbreeding occurred before those populations split. The timing makes the Middle East the likeliest place where humans leaving Africa and resident Neanderthals did the deed.

Does this mean that Neanderthals didn’t interbreed with Europeans more recently?

Not necessarily – it’s just that earlier interbreeding is more likely to leave a mark on our genomes than more recent trysts, largely because of population expansion. With a more complete Neanderthal genome and DNA from other Neanderthals, it will be possible to find out if Europeans and Asians interbred with Neanderthals after those groups went their separate ways.

Archaeological evidence suggests that humans and Neanderthals overlapped for about 10,000 years in Europe and some fossils have even been interpreted as Neanderthal-human hybrids, though not all palaeoanthropologists agree on this.

Can we trace any human traits back to Neanderthals?

Probably not. Some researchers had hypothesised that some human genes, including one involved in brain development, originated from interbreeding with Neanderthals, but Pääbo’s team found no evidence for this. In fact, no Neanderthal DNA sequences are consistently found in humans. “Each person has a different bit of Neanderthal in them,” says Reich.

However, Sarah Tishkoff, a geneticist at the University of Pennsylvania in Philadelphia not involved in the project, says it is possible that interbreeding introduced traits into a few human populations. “It will be interesting to look at other ethnic groups and other Neanderthals,” she says.

Does the Neanderthal genome explain what makes us different from them?

That is the hope, though this first scan emphasises the overwhelming similarity between humans and Neanderthals. Pääbo’s team found just 78 amino acid peculiarities – differences that change the shape and potentially the function of a protein – which all humans have in their genes but Neanderthals didn’t. To put that in context, the genome encodes about 10 million amino acids. They also identified more than 200 regions of the human genome that look like they have evolved since we split from Neanderthals.

These changes occurred in genes linked to cognition, skin and bone development, and reproduction, but they don’t explain what makes us human, because they occurred after humans split from Neanderthals 500,000 years ago.

“There is no compelling story where you say, ‘Ah, ah, this difference means this,'” Green says. “‘It let us write poetry instead of making stone tools’ – there’s nothing that jumps out like that.”

That means a lot of hard work for researchers, examining the genetic differences between humans and Neanderthals one by one, and in some cases genetically engineering bacteria, mice and other organisms with these genes. “This is really a gold mine for finding recent changes in human evolution,” Green says.

Does this mean we could clone a Neanderthal?

No. “Resurrecting” a Neanderthal based on its genome sequence poses a number of scientific and technological problems, not to mention ethical dilemmas.

The most straightforward way to bring Neanderthals back to life would be to alter the DNA of a human cell to match that of Neanderthals and then transplant its nucleus into an unfertilised egg and implant it into a surrogate mother, a process called somatic cell nuclear transfer (SCNT). No one has accomplished this feat for humans, and it may not be possible.

Even if we could clone humans, another challenge would be introducing the millions of genetic differences that exist between humans and Neanderthals into a human cell. As it stands, the Neanderthal genome is incomplete and riddled with errors.

More problematic, though, is making many genetic mutations at once instead of one at a time, as is conventionally done. A technology exists to introduce dozens of mutations at a time into bacteria but this doesn’t come close to the complexity required to make a Neanderthal.

Journal reference: Science, DOI: 10.1126/science.1188021