Mammoth Genes Decoded — Clones on the way?

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Using hairs from woolly mammoths, scientists have sequenced an extensive genome of these elephant cousins, a new report says.

The development brings researchers a step closer to “resurrecting” the extinct species via cloning, though so many technical obstacles stand in the way that some experts doubt it could ever happen.

(See “Mammoths to Return? DNA Advances Spur Resurrection Debate” [June 25, 2007].)

The study is said to be the first ever decoding of an extinct species’ nuclear DNA, which contains vast amounts information.

Once interpreted, the genetic data will give researchers unprecedented access to the biology and evolution of woolly mammoths, which began dying out after the end of the last ice age, about 10,000 years ago.

Technological Leap

“What our paper shows, for the first time, is that it is possible to sequence the genome of an extinct animal almost as well and as efficiently as a modern genome,” said Stephan Schuster of Pennsylvania State University, one of the two project leaders.

The technique could be used to sequence the genomes of Neanderthals, and early humans—but not dinosaurs, which went extinct too long ago for their DNA to be viable today, according to the researchers.

Nuclear DNA resides in cell nuclei and is difficult to salvage from ancient bones. For one thing, it’s far less plentiful than mitochondrial DNA, which is passed down only by mothers. The mitochondrial genome of the woolly mammoth was completely sequenced in 2006.

(Related: “Woolly Mammoth DNA Reveals Elephant Family Tree” [December 20, 2005].)

Nuclear DNA, however, carries much more genetic data, including just about all information about particular traits and physical characteristics.

Giant Genome

The woolly mammoth genome is, indeed, “mammoth.”

The researchers sequenced more than half of the woolly mammoth’s estimated 4.7 billion base pairs#8212;far more than has ever been done before for the species.

At an estimated 4.7 billion base pairs, the full woolly mammoth genome is by far the largest of any known mammal genome, scientists say—though they’re not exactly sure why. (Base pairs make up each rung of the “DNA ladder,” representing the “letters” of the genetic code.)

“What we do know is that the elephant genome and the mammoth genome are very large—by far the largest mammallian genome,” said Michael Hofreiter of the Max Planck Institute for Evolutionary Anthropology in Germany, who was not involved with the study.

“It’s kind of striking, and its very odd,” Hofreiter said of the new genome’s size. “It’s hard to say what it would mean evolutionarily.”

Hair Helps

Woolly mammoths have always been good candidates for ancient DNA studies, because many remains have been relatively well preserved in the permafrost of northern Europe, Asia, and North America, where the beasts roamed for hundreds of thousands of years.

Still, even frozen mammoth DNA is often unsalvageable, due to damage, decay, and contamination with the DNA of other organisms, such as bacteria.

Study co-leader Schuster said the team got around this problem by studying nuclear DNA from strands of hair—in this case, from the remains two animals found in Russia’s Siberia region.

(Related: “Mammoth Hair Yields Ancient DNA, Study Says” [September 27, 2007].)

“The hair shaft is like a biological plastic,” Schuster said. “It perfectly seals the DNA, and the bacteria [can’t] infect it.”

The Findings

At this point, the sequenced woolly mammoth genome is more about potential than conclusions.

Régis Debruyne, of McMaster University in Canada, also studies mammoth DNA but was not involved with the study.

Debruyne described the sequence as “basically millions of loose pieces of the puzzle that need to be assembled and identified” before conclusions about traits can be drawn.

The genome is “only the beginning of the story,” agreed Max Planck’s Hofreiter, who wrote an accompanying article about the study’s genetic implications, which, like the study, will appear in tomorrow’s issue of the journal Nature.

As for what the genome might lead to, evolutionary geneticist Hendrik Poinar of McMaster University said the data will eventually reveal “what makes a mammoth a mammoth and not an elephant.”

Genetic Diversity

Penn State biologist Webb Miller, who co-led the new study with Schuster, said sequencing the mammoth genome could help save today’s endangered species.

Miller and Schuster said woolly mammoths had relatively little genetic diversity, and that may have contributed to their inability to adapt to a new climate after the Ice Age.

“If the climate changes and you have little genetic diversity, then it is very difficult for you to respond to that challenge,” Schuster explained.

That is, it’s tougher for a species to evolve into a better adapted version of itself if it does not have a variety of types for natural selection to “choose” from.

“We’re thinking that the susceptibility of a species to extinction is not measured by the number of living animals of the species but rather by diversity in the nuclear genomes,” Miller said.

Max Planck’s Hofreiter noted that the nuclear DNA of only two mammoths, as published today, “is not enough to make any comprehensive analysis of diversity.”

It can be said, however, that, based on the two samples, mammoths were at least as genetically diverse as humans.

Mammoth Clones?

The new genome could also lead to living, breathing woolly mammoths, some experts say.

Present-day elephants would be key to any such cloning project.

First, all genetic differences between mammoths and elephants would have to be identified.

Next, an elephant egg would have to be fertilized with altered genes and implanted in the womb of a female elephant.

“Theoretically it’s not completely out of the question,” Hofreiter, of the Max Planck Institute, said.

“But I see so many problems that I can’t imagine it would ever work.”

The bigger point, Hofreiter added, is that “the tons of money you would need to resurrect a mammoth would probably be better spent saving endangered species.”

Miller, who co-led the study with Schuster, said, “Resurrecting mammoths is a relatively boring thought. When we can do that, we’ll be able to clone humans. … My basketball team will be unbeatable.”