By David Brown
Washington Post Staff Writer
Thursday, November 20, 2008
An international team of scientists has reconstructed about two-thirds of the genome of the woolly mammoth using DNA extracted from balls of hair, the first time this has been accomplished for an extinct species.
The project provides some of the starting material that would be required to bring back to life the giant, hairy, cold-weather animals. That task, however, is not likely to be accomplished soon -- and may turn out to be impossible.
The research offers insight into the history of elephants, however. It may illuminate the evolutionary adaptations that did -- and did not -- occur in mammoths as their habitat and the climate changed eons ago. The research also suggests that samples of fur, including many in museum collections, may be more useful than scientists thought in studying extinct species.
"One can imagine a new field of 'museomics' using the collected samples that are now stored in natural history museums," said Stephan C. Schuster, a biologist at Pennsylvania State University who led the 21-person research team with a colleague, Webb Miller.
"This is definitely heading in the right direction toward acquiring an extinct genome, which is really cool," said Hendrik Poinar, a molecular biologist at McMaster University in Ontario. He has worked on other projects using "fossil DNA" but was not involved in this one.
Mammoths disappeared about 10,000 years ago when they were hunted to extinction by prehistoric humans. The lineages that gave rise to Asian elephants and woolly mammoths diverged from a common ancestor about 7 million years ago. The lineage that led to African elephants had split off less than a million years before that.
The researchers, who are reporting their results today in the journal Nature, used two samples of woolly mammoth hair. One was from a 20,000-year-old mammoth from Siberia; they paid $130 for a four-ounce handful collected legally by Siberian natives. The other was from a specimen from an animal that died 65,000 years ago.
Schuster and his colleagues read the sequence of genetic letters from fragments of DNA inside the shafts of the hair. The DNA is left from cells that produce the hair protein and then stack up and die as the hair grows. The chief advantage of using this source is that the DNA is largely protected from contamination by microbial DNA, which muddies the picture.
The mammoth DNA had degraded into very short strands of no more than a few hundred bases, or letters of genetic code, strung end-to-end. In intact cells, DNA strands can be tens of millions of bases long.
The researchers sequenced 4.17 billion bases and determined that 3.3 billion belonged to the mammoths. The rest were from viruses, bacteria, fungi and other microbes. The researchers identified the mammoth DNA by comparing the sequences with the genome of the modern African elephant. Sequences that were extremely close were assumed to have come from the mammoth, not from the microbial contaminants.
Elephant and mammoth genomes are very large, probably 4.7 billion bases, considerably longer than the 3 billion-base human genome. This suggests that Schuster and his colleagues captured about 70 percent of the mammoth genome.
Their preliminary analysis shows that mammoths and elephants differed by 0.6 percent of their DNA. That is about half the difference between human beings and their closest relatives, chimpanzees.
Elephants evolved in a tropical habitat, and the species surviving today live only in very warm places. Their chief problem is dispersing the heat generated by their massive bodies. Woolly mammoths apparently moved into the Arctic about 2 million years ago. Their chief problem was conserving body heat, exactly the opposite.
How mammoths were able to adapt through natural selection to such different conditions -- while remaining 99.4 percent identical to elephants -- is a matter of intense interest to evolutionary biologists.
"It was relatively rapid shift, a relatively recent shift and a dramatic change," said Michael Hofreiter, a molecular geneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.
Mammoths are among the few mammals that re-evolved the ability to grow thick hair, a capacity their ancestors had lost. They had other heat-saving features, such as small ears and short tails. But the most interesting changes almost certainly involve metabolism, use and storage of fat, and circulation.
"That's what we really want to learn -- what made a mammoth a mammoth," Poinar said.
Curiously, there is evidence that natural selection may ultimately have failed at least one limb of the woolly mammoth family tree.
Schuster and his colleagues determined that the 65,000-year-old animal was from a subspecies that died out about 45,000 years ago. That was before there were human beings in Siberia to hunt it.
"You have to ask: How can a species that made it through so many ice ages suddenly go extinct?" Schuster said. "It seemed that the genetic outfit of that mammoth did not have enough 'plasticity' anymore for it to deal with challenges coming from the environment."
As for bringing mammoths back to life, that is still firmly the domain of science fiction. It would require retrofitting an elephant cell with hundreds of thousands of mammoth-making mutations or building the nucleus of a mammoth cell from scratch -- both impossible at the moment.
J. Craig Venter, one of the sequencers of the human genome, has synthesized from chemical compounds the genes of a bacterium, Mycoplasma genitalium.
"We have not yet booted it up," he said yesterday, referring to the next step of putting the manmade genes into a bacterium whose native genes have been removed to see whether the whole thing will grow and divide.
He does not think there will be baby mammoths anytime soon.
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