You and Your Neanderthal Relatives

You are 1 to 4% Neanderthal. That's what Carl Zimmer is reporting in this posting on his Discover Magazine blog:

In the 1990s, the geneticist Svante Pääbo led a team of scientists in search of a new kind of evidence to test these ideas: ancient DNA. They were able to extract bits of DNA from bones that were found along with Schaafhausen’s skull cap in the Neander valley cave. Despite being 42,000 years old, the fossils still retained some genetic material. But reading that DNA proved to be a collossal challenge. Over thousands of years, DNA breaks into tiny pieces, and some of the individual “letters” (or nucleotides) in the Neanderthal genes become damaged, effectively turning parts of its genome into gibberish. It’s also hard to isolate Neanderthal DNA from the far more abundant DNA of microbes that live in the fossils today. And the scientists themselves can contaminate the samples with their own DNA as well.

Over the years,Pääbo and his colleagues have found ways to overcome a lot of these problems. They’ve also taken advantage of the awesome leaps that genome-sequencing technology has taken since they started the project. They have been able to reconstruct bigger and bigger stretches of DNA. They’ve been able to fish them out of a number of Neanderthal fossils from many parts of the Old World. And today they can offer us a rough picture of all the DNA it takes to be a Neanderthal.

To create a rough draft of the Neanderthal genome, the scientists gathered DNA from the fossils of individual Neanderthals that lived in Croatia about 40,000 years ago. The scientists sequenced fragments of DNA totalling more than 4 billion nucleotides. To figure out what spot on which chromosome each fragment belonged, they lined up the Neanderthal DNA against the genomes of humans and chimpanzees. They are far from having a precise read on all 3 billion nucleotides in the Neanderthal genome. But they were able to zero in on many regions of the rough draft and get a much finer picture of interesting genes.

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The scientists compared the variants in the Neanderthal genome to those in humans to figure out when the two kinds of humans diverged. They estimate that the two populations became distinct between 270,000 and 440,000 years ago. After the split, our own ancestors continued to evolve. It’s possible that genes that evolved after that split helped to make us uniquely human. To identify some of those genes,Pääbo and his colleagues looked for genes that were identical in Neaderthals and chimpanzees, but had undergone a significant change in humans.

They didn’t find many. In one search, they looked for protein-coding genes. Genes give cells instructions for how to assemble amino acids into proteins. Some mutations don’t change the final recipe for a protein, while some do. Pääbo and his colleagues found that just 78 human genes have evolved to make a new kind of protein, differing from the ancestral form by one or more amino acids. (We have, bear in mind, 20,000 protein-coding genes.) Only five genes have more than one altered amino acid.

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If you believe the difference between humans and Neanderthals is primarily in the way we think, then you may be intrigued by the strongly selected genes that have been linked to the brain. These genes got their links to the brain thanks to the mental disorders that they can help produce when they mutate. For exampe, one gene, called AUTS2, gets its name from its link to autism. Another strongly-selected human gene, NRG3, has been linked to schizophrenia. Unfortunately, these disease associations just tell scientists what happens when these genes go awry, not what they do in normal brains.

The most satisfying hypothesis the scientists offer is also the one with the deepest historical resonance. It has to do with the brow ridge that so puzzled Schaafhausen back in 1857. One of the strongly selected genes in humans, known as RUNX2, has been linked to a condition known as cleiodocranial dysplasia. People who suffer from this condition have a bell-shaped rib cage, deformed shoulder bones, and a thick brow ridge. All three traits distinguish Neanderthals from humans.

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On the other hand, some scientists looking at other genes have found what they claim to be evidence of interbreeding. They would find gene variants in living humans that had evolved from an ancestral gene about a million years ago. One way to explain this pattern was to propose that modern humans interbred with Neanderthals or other hominins. Some of their DNA then entered our gene pool and has survived till today. In one case, a team of scientists proposed that a gene variant called Microcephalin D hopped into our species from Neanderthals and then spread very quickly, driven perhaps by natural selection. Making this hypothesis even more intriguing was the fact that the gene is involved in building the brain.

Pääbo and his colleagues looked for pieces of the Neanderthal genome scattered in the genomes of living humans. The scientists found that on average, the Neanderthal genome is a little more similar to the genomes of people in Europe, China, and New Guinea, than it is to the genomes of people from Africa. After carefully comparing the most similar segments of the genomes, the scientists propose that Neanderthals interbred with the first immigrants out of Africa–perhaps in the Middle East, where the bones of both early humans and Neanderthals have been found.

Today, the people of Europe and Asia have genomes that are 1 to 4 percent Neanderthal.That interbreeding doesn’t seem to have meant much to us, in any biological sense. None of the segments our species picked up from Neanderthals was favored by natural selection. (Microcephalin D turns out to have been nothing special.)

This story gets more and more exciting as the science progresses. I can hardly wait for when the understand what these genes that we share with Neanderthals do. I also want to understand what the genes that are distinctly human do. Over the next 50 to 100 years that will all be fully understood. I would love to be around to hear the whole story, but sadly I won't be here for the punch line. Oh well. It is fun just to kibitz the science.