Scientists Sequence Half the Woolly Mammoth's Genome

Study could be a step toward resurrecting a long-extinct animal

Photo by S.C. Schuster

Editor's note: This story will appear in our January issue but is being posted early because of a publication in today's Nature.

Thousands of years after the last woolly mammoth lumbered across the tundra, scientists have sequenced a whopping 50 percent of the beast’s nuclear genome,  they report in a new study. Earlier attempts to sequence the DNA of these icons of the Ice Age produced only tiny quantities of code. The new work marks the first time that so much of the genetic material of an extinct creature has been retrieved. Not only has the feat provided insight into the evolutionary history of mammoths, but it is a step toward realizing the science-fiction dream of being able to resurrect a long-gone animal.

Researchers led by Webb Miller and Stephan C. Schuster of Pennsylvania State University extracted the DNA from hair belonging to two Siberian woolly mammoths and ran it through a machine that conducts so-called highthroughput sequencing. Previously, the largest amount of DNA from an extinct species comprised around 13 million base pairs—not even 1 percent of the genome. Now, writing in the November 20 issue of Nature, the team reports having obtained more than three billion base pairs. “It’s a technical breakthrough,” says ancient-DNA expert Hendrik N. Poinar of McMaster University in Ontario.

Interpretation of the sequence is still nascent, but the results have already helped overturn a long-held assumption about the proboscidean past. Received wisdom holds that the woolly mammoth was the last of a line of species in which each one begat the next, with only one species existing at any given time. The nuclear DNA reveals that the two mammoths that yielded the DNA were quite different from each other, and they seem to belong to populations that diverged 1.5 million to two million years ago. This finding confirms the results of a recent study of the relatively short piece of DNA that resides in the cell’s energy-producing organelles—called mitochondrial DNA—which suggested that multiple species of woolly mammoth coexisted. “It looks like there was speciation that we were previously unable to detect” using fossils alone, Ross D. E. MacPhee of the American Museum of Natural History in New York City observes.

Thus far the mammoth genome exists only in bits and pieces: it has not yet been assembled. The researchers are awaiting completion of the genome of the African savanna elephant, a cousin of the woolly mammoth, which will serve as a road map for how to reconstruct the extinct animal’s genome.

Armed with complete genomes for the mammoth and its closest living relative, the Asian elephant, scientists may one day be able to bring the mammoth back from the beyond. “A year ago I would have said this was science fiction,” Schuster remarks. But as a result of this sequencing achievement, he now believes one could theoretically modify the DNA in the egg of an elephant to match that of its furry cousin by artificially introducing the appropriate substitutions to the genetic code. Based on initial comparisons of mammoth and elephant DNA, he estimates that around 400,000 changes would produce an animal that looks a lot like a mammoth; an exact replica would require several million.

(The recent cloning of frozen mice is not applicable to woolly mammoths, Schuster believes, because whereas mice are small and therefore freeze quickly, a mammoth carcass would take many days to ice over—a delay that would likely cause too much DNA degradation for cloning.)

In the nearer term, biologists are hoping to glean insights into such mysteries as how woolly mammoths were adapted to their frigid world and what factors led to their demise. Miller notes that by studying the genomes of multiple mammoths from different time periods, researchers will be able to chart the decrease in genetic diversity as the species died out. The downfall of the mammoths and other species may contain lessons for modern fauna in danger of disappearing, he says.

Indeed, the team is now sequencing DNA they have obtained from a thylacine, an Australian marsupial that went extinct in 1936, possibly as a result of infection. They want to compare its DNA with that of the closely related Tasmanian devil, which is currently under threat from a devastating facial cancer.

“We’re hoping to learn why one species went extinct and the other didn’t and then use that [knowledge] in conservation efforts,” Miller says. If the research turns up genes associated with survival, scientists can use that information to develop a breeding program for the Tasmanian devil that maximizes the genetic diversity of the population—and increases the frequency of genes that confer immunity. Perhaps the greatest promise of ancient DNA is not raising the dead but preserving the living.

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