Code of the Caveman A new DNA mapping technique may solve an ancient mystery: Do modern humans carry Neanderthal genes?
By Annalee Newitz Wired Magazine Issue 14.07 - July 2006 http://www.wired.com/wired/archive/14.07/caveman.html On a forest-choked expanse of land that will one day be called Germany, a herd of bison huddles together to ward off the cold. Hidden in the foliage nearby squats a man. Like the animals hes hunting, he has evolved over hundreds of thousands of years to cope with freezing temperatures. His massive jaw juts out, and his forehead slopes forward to form a heavy brow providing a thick layer of bone that protects his sinuses and large brain from the icy air. His barrel-shaped body and short limbs help him retain heat. So do the furs he wears and the fires his family builds in the cave where they live. In one hand, he carries an object that represents the height of technology among his people: a knife-edged stone made by a skilled craftsman who strikes one rock with another, 40 or 50 times with absolute precision, flaking off tiny shards until an extremely sharp blade emerges. Technology isnt enough to fell the bison, though. Gored and trampled, the man dies without bringing dinner home to his family. His people eventually die out, leaving behind only a few bones and fragments of stone. We dont know why they became extinct or what they called themselves. We know them only by the name our species has given them: Homo neanderthalensis, the Neanderthals. Forty thousand years after the bison hunter went down, a tall, lanky man with disheveled white hair and scuffed hiking shoes is using one of his species own state-of-the art tools to pulverize the Neanderthal even further. On a warm spring day in Walnut Creek, California, geneticist Eddy Rubin stands surrounded by huge glass tanks. Inside, robotic arms move with frenetic precision over plates holding genetic material, reducing the Neanderthals remains to tiny strings of nucleotides and producing the worlds first extended sequence of Neanderthal DNA. The data will help pinpoint when humans and Neanderthals diverged on the evolutionary tree and if they bore children together when they met again as separate species. The information may also help answer a profoundly human question: Are we the first and only intelligent species to walk the planet? If it turns out that we do share certain key genes with the Neanderthals, well know more about whether their intellectual capacities matched our own, including whether they might have had a spoken language. Humans and Neanderthals share a common ancestor, Homo erectus; some of them migrated north out of Africa more than a million years ago and evolved into Neanderthals. Meanwhile, in the relative warmth of Africa, Homo erectus evolved into Homo sapiens. One hundred thousand years ago, during a brief thaw in the ice age that had swept across Eurasia, Homo sapiens migrated out of Africa, eventually arriving at the Neanderthals European domain 65,000 years later. The two groups shared territory for somewhere between 5,000 and 10,000 years. Humans and Neanderthals occupied adjacent caves for thousands of years, and we have a lot of speculations about them based on a few bones and stones, Rubin says. But as we analyze the genome, we have the opportunity to learn more about their skin and hair color, as well as what they ate and even their language. The more he talks, the more excited Rubin gets. Hes convinced he is close to solving a mystery that has haunted anthropologists since the first Neanderthal skeleton was discovered in 1856 in a German valley (or thal) called Neander. Finally he bursts out, Soon well know whether Neanderthal males like this one contributed their genes to modern-day Homo sapiens! Trained as a biophysicist, Rubin has spent the past two decades working in genetics, climbing to the top of his field and becoming head of two of the nations most prestigious gene sequencing labs: the Joint Genome Institute in Walnut Creek and the genomics division of UCs Lawrence Berkeley National Laboratory. I dont really like cells or anything, he says. I just like data. Rubin first became interested in sequencing a Neanderthal in 1997, when a researcher named Svante Pääbo at Germanys Max-Planck Institute for Evolutionary Anthropology published the results of an early effort to read Neanderthal DNA. Pääbo and his team examined mitochondrial DNA tiny loops of genetic material found in the hundreds of power plants that exist in each cell. Unfortunately, they just dont contain that much information. Nonetheless, when Pääbo and his team announced that no Neanderthal mitochondrial DNA had found its way into Homo sapiens, the press and scientific community went wild. The story made the cover of the prestigious scientific journal Cell, and it was the subject of a New York Times story and a Nova special. As soon as he could, Rubin caught a plane to Leipzig. Neanderthals, he says, are cool. They get people excited about science and evolution, and that is how you fight the dark forces. Pääbo and Rubin became hiking buddies, and six years ago a walk they took turned into a discussion of getting better Neanderthal data by using chromosomal DNA, which is much more comprehensive than the small snips found in mitochondria. Rubins team at LBNL would read the genes by sandwiching in some time on the JGIs massive sequencing farm. Pääbo was thrilled. But the anthropology community, which keeps its few dozen Neanderthal bone fragments carefully preserved in museums, wasnt keen on giving precious samples to a couple of genetics geeks. So Rubin and Pääbo sequenced the ancient cave bear, a creature whose bones are quite plentiful. That success helped Rubin and Pääbo persuade two museums to part with a few ounces of Neanderthal bone. In late fall 2005, Rubin took the sample back to his laboratory, mashed it up, and began to figure out the exact genetic makeup of Homo neanderthalensis. Now I watch as techs at the Joint Genome Institute arrange prepared DNA samples on thick, translucent plates and feed them into ABI 3730 machines that resemble giant photocopiers. Hair-thin tubes called capillaries then sip genetic material from the plates and run it past a sensor that determines which of four possible nucleotides is in the sample. Rubin shows me a small monitor attached to one of the ABIs. Mesmerized, I watch as colored bars representing A, T, G, and C appear on the screen. Each brings us one nucleotide closer to answering a question thats 150 years old. A process called metagenomics, pioneered by forensic analysts to sort DNA from a contaminated crime scene, is what makes it possible to sequence DNA from a few ounces of a long-buried bone adulterated by 40,000 years worth of microbes. Typical sequencing involves looking at loads of genetic material from one life-form. Metagenomics takes a jumbled sample and sequences everything in it be it plants, microbes, or lab workers DNA. Once everything in Rubins sample is sequenced this way, he uses powerful bio-informatics software to separate out likely Neanderthal DNA. This sifting process is a simple pattern-matching exercise: The software compares each strand of DNA with other known sequences, eliminating anything that doesnt look hominid. DNA from modern humans wont show the predicted level of decay that can be tossed out, too. This process was impossible just a few years ago, before computers as fast as Rubins and vast databases of gene sequences. Now all we have to do is wait for the results. Weeks pass, and I keep pestering Rubin about what his team has found. At last, Rubin calls me. Big news, he says. His first major conclusion is that humans and Neanderthals diverged into recognizably separate groups about 500,000 years ago, a date anthropologists have long sought to pin down. He and his team determined this by counting the differences between select sequences of the Neanderthal genome and the human genome. Since mutations usually occur at a predictable rate, it was easy to tell when the species split. But thats not all. The evidence suggests very strongly that Neanderthal men didnt pass on any genetic material to modern humans, he says. The Neanderthal DNA that Rubin analyzed is simply too different from our own. Its a conclusion that will fuel flame wars on academic message boards for years. Rubin pauses dramatically, and then continues: This is a tremendous blow to the theory of admixture between humans and Neanderthals. Or at least he thinks it is. Not everyone is giving up on the possibility that humans and Neanderthals shared more than hunting grounds back in the Upper Paleolithic. An anthropologist at Washington University in St. Louis, Erik Trinkaus is a fierce proponent of the theory that humans and Neanderthals interbred. In 1999, his team examined a 28,000-year-old skeleton, and Trinkaus claimed that its morphological features were exactly what youd expect in a hybrid population. Rubin dismisses the analysis of bone structure for which Trinkaus is famous, comparing anthropologists to phrenologists. He adds that lots of things can appear different in the bone structure of two organisms even if their genomes are very similar. Trinkaus shoots back, Genetics is trendy now. But theyre only looking for the presence of Neanderthal genes in current populations and that doesnt tell you what happened 30,000 years ago. He says that Neanderthals and humans could have mated but produced offspring that didnt thrive; those hybrid genomes would have been eliminated over the generations by natural selection. In such a scenario, the genetic footprint left by Neanderthals in the human genome would be vanishingly small. Rubin is willing to concede that its possible humans and Neanderthals interbred. It would be hard to know for sure whether there had been intermixing if Neanderthal genes had been selected out of the contemporary population. But Rubin doesnt think its likely, given the differences hes found between the two genomes. Not only that, Rubin believes offspring of individuals from such divergent groups would probably have been sterile, like mules. That hunter freezing in Germany probably wasnt my distant European ancestor after all. In the end, because of decay in the bone sample, Rubins team was able to read only 76,000 base pairs from the Neanderthal a tiny slice, if you consider that the completed human sequence is 3 billion base pairs long. It was enough for him to be confident that were probably not carrying Neanderthal genes, but not enough to tell him everything he wants to know. If he had a complete genome, he could look for genes like FOXP2, which is found in songbirds and humans and is associated with the complex vocalizations that are the hallmark of language. And he wants to hunt for unique Neanderthal mutations in genes like AHI1, which is connected to brain development. Hes also eagerly anticipating the day when we understand the human genome well enough to figure out which alleles, or alternate forms of a gene, code for physical features like skin color and hair texture. Once we know that, researchers can return to the Neanderthal and look for similar alleles. To encourage this kind of research, Rubin is making his Neanderthal sequence publicly available on GenBank, an online resource for researchers. Hes also creating test tubes and plates of genetic material that can be reproduced and shipped anywhere. Rubins work is likely to be published this summer. It will stir up the scientific community, but Rubin is more interested in planning how hell build out his library of Neanderthal DNA. I need to get more bone, he says. Ill go to Russia with a pillowcase and an envelope full of euros and meet with guys who have big shoulder pads. Whatever it takes." ================================================= George Antunes Voice (713) 743-3923 Associate Professor Fax (713) 743-3927 Political Science Internet: antunes at uh dot edu University of Houston Houston, TX 77204-3011 Reply with a "Thank you" if you liked this post. _____________________________ MEDIANEWS mailing list [email protected] To unsubscribe send an email to: [EMAIL PROTECTED]
