Old bone helps crack Neanderthal DNA
Using a 38,000-year-old bone fragment found in a Croatian cave, scientists have decoded a section of DNA from humanity’s closest related species -- the long-extinct and enigmatic Neanderthal.
The reports, published concurrently today in the journals Nature and Science, demonstrate the feasibility of squeezing genetic information out of fossils -- a new way of probing the ancient past that until now has been glimpsed primarily through scattered bones and artifacts.
“The sequence data will serve as a DNA time machine that will tell us about biology and aspects of Neanderthals that we could never get from their bones,” said Edward Rubin, director of the genomics division at Lawrence Berkeley National Laboratory and senior author of the report in Science. Among other things, he said, it could shed light on what caused Neanderthals to disappear from Europe about 30,000 years ago, shortly after modern humans moved into their territory.
A complete Neanderthal genome would help scientists zero in on a fundamental question: What makes humans human?
So far, researchers have sequenced about 1 million out of an estimated 3 billion base pairs of the Neanderthal genome. They expect it will take two years to complete a full draft.
“I’m super-excited about this project,” said Katherine S. Pollard, an assistant professor at the UC Davis Genome Center. She is looking for genes important to human evolution by comparing them with genes from chimpanzees, humans’ closest living relative. “Neanderthals are perfect [to study] because they are actually our closest relative amongst all species that we know have ever lived.”
Even the preliminary sequences contain enough information to calculate that Homo neanderthalis and Homo sapiens shared at least 99.5% of their DNA. The characteristics that make humans unique are contained in the remaining 0.5%.
“This is just a toe in the water, but ultimately we’ll be able to identify genes in Neanderthals that seem to be important in people and see if they have the same one,” said Richard G. Klein, a paleoanthropologist at Stanford University.
The genetic analysis was not precise enough to pinpoint the first branching of the human and Neanderthal lineages.
Rubin’s group estimated that the ancestors of humans and Neanderthals began to genetically diverge about 706,000 years ago. Another team publishing in Nature calculated the divergence occurred 516,000 years ago. The fossil record suggests a split time of 400,000 years ago.
These prehistoric beings gradually accumulated small genetic mutations that were not outwardly visible at first but ultimately resulted in separate species.
Fully evolved Neanderthals are thought to have arisen about 130,000 years ago, settling in Europe and western Asia. Modern Homo sapiens emerged at roughly the same time in Africa.
As humans pushed their way into Eurasia 40,000 to 50,000 years ago, they came in contact with their long-separated cousins. Within 10,000 to 20,000 years, the Neanderthals had disappeared.
One of the most hotly contested topics in paleoanthropology is whether the two species interbred while they both inhabited Europe and Asia. Scientists are eager to search for evidence of Neanderthal genes in human DNA, and vice versa.
For example, Bruce Lahn, a professor of human genetics at the University of Chicago, has proposed a controversial theory that humans living among Neanderthals may have inherited a Neanderthal gene called microcephalin that regulates brain size.
“Our biological evolution has actually benefited from mating with our relative species that have gone extinct,” said Lahn, who wasn’t involved with the gene sequencing. “That’s the exciting part. Parts of them do live on in our genes.”
The DNA sequences decoded so far don’t provide support for the microcephalin theory, Rubin said, but neither have they ruled it out.
The Nature team found evidence that human males may have contributed some of their DNA to the Neanderthal genome. The genes on the Neanderthal’s X chromosome include too many mutations found in the human lineage to have occurred through chance, said Michael Egholm of 454 Life Sciences and coauthor of the Nature paper.
Svante Paabo, a pioneer in decoding ancient genomes, tested more than 70 Neanderthal specimens over two years and found only one that contained enough DNA to sequence. It came from part of a femur discovered in Croatia’s Vindija cave in 1980.
“This particular bone is rather small and uninteresting,” said Paabo of the genetics department at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and senior author of the Nature study. “It was sort of thrown in a big box of uninformative bones in the museum in Zagreb and not handled very much by people. More interesting bones have been extensively cleaned and handled and thus tend to be much more contaminated.”
Examining a 100-milligram sample, Paabo’s team found that more than half of the DNA sequences were from bacteria that had been growing on the bone for 38,000 years. A small amount was human DNA from modern handlers of the bones, and the rest belonged to the Neanderthal.
The researchers were able to clearly distinguish the Neanderthal DNA because of telltale signs of chemical damage that occur over time. In addition, the strings of DNA nucleotides -- commonly known by the chemical letters A, T, C and G -- were typically only 50 or 60 base pairs long, whereas samples from humans were usually at least twice as long.
Paabo’s group used a new technology developed by 454 Life Sciences called pyrosequencing to decode about 1 million of the Neanderthal base pairs. Using a different sequencing strategy, Rubin’s team at the U.S. Department of Energy Joint Genome Institute unraveled about 65,000 base pairs.
The sequencing of Neanderthal DNA is the biggest success so far in the budding field of paleogenetics.
It began with Paabo in 1986, when he first retrieved DNA from ancient mummies. In 1997 he extracted mitochondrial DNA from Neanderthals. But that DNA, which is passed from mother to child, contains far less information than the nuclear DNA reported on today.
“Twenty years ago there was a raging argument about whether Neanderthals could be the ancestors of living human beings,” Klein said. “Based on the fossils it seemed irresolvable. Then came the mitochondrial DNA evidence. It showed that all living humans shared a relatively recent ancestor in Africa from a time after Neanderthals were extinct. Genetics settled that.”
For the new studies, Paabo and Rubin practiced their sequencing techniques using genes from extinct cave bears, whose fossilized remains are relatively abundant. Last summer, a group from the University of Leipzig reported the discovery a well-known gene for hair color in DNA from a 43,000-year-old mammoth bone. They concluded that mammoth fur may have come in a variety of colors.
Some scientists have discussed the possibility of cloning the mammoth or other prehistoric beasts. But Paabo and Rubin said cloning a Neanderthal was inconceivable.
Efforts to clone human embryos using purified DNA have so far failed, Paabo said, and it’s even more farfetched “to imagine how this would ever be done with something that’s degraded, chemically modified and mixed in with ... bacterial DNA.”
Paabo also discounted the possibility of sequencing DNA from more distant relatives, such as Homo erectus, which became extinct about 300,000 years ago.
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