American Museum of Natural History Biologist and Colleagues Decode Longest DNA Sequence Ever of Woolly Mammoth

An American Museum of Natural History biologist and his colleagues have completed a painstaking project that allowed them to decode the largest piece by far of the genome of the woolly mammoth, the shaggy, extinct elephant relative that ranged far and wide on Earth until the end of the last Ice Age about 10,000 years ago. This success demonstrates beyond a doubt that the entire genome of the woolly mammoth could, in principle, be sequenced quite soon. The procedure involved separating mammoth DNA from that of other specimens found in a fossilized sample and identifying approximately 13 million base-pairs, elements of DNA that match that of living elephants. This small but significant percentage of the entire woolly mammoth genetic code is nearly 500 times longer than any woolly mammoth sequence previously identified, including results announced early this week with a less functionally important type of DNA.

Arriving at the full genome of even living animals is remarkable, given that the human genome was sequenced only six years ago. As of last week, scientists had published the complete genomes of 332 organisms, mostly single-celled organisms and none extinct.

The new study by Ross D. E. MacPhee, Curator in the Museum's Department of Mammalogy, along with Hendrik N. Poinar and Carsten Schwarz of McMaster University, Ji Qi of Penn State University, Beth Shapiro of Oxford University, and others, is published in the latest issue of the journal Science.

The team analyzed DNA obtained from the cell nuclei (nuclear DNA) of a 27,000-year-old fossilized female mammoth (Mammuthus primigenius) jawbone, an exceptionally well-preserved specimen recovered in Siberia near Lake Taimyr, a freshwater lake north of the Arctic Circle. The scientists found that the specimen DNA nearly perfectly matched the known genetic code of today's African elephants (Loxodonta africana), one of mammoths' closest living relatives. Analysis of the specimen involved extracting its DNA, determining whether the DNA remained intact, amplifying it to obtain sufficient quantities for analysis, and distinguishing the mammoth DNA from that of other organisms in the sample, such as other mammals, fungi, plants, and bacteria.

"This new genomic sequence of the woolly mammoth is orders of magnitude better than any previous result," said Dr. MacPhee, "and it raises the possibility that scientists could sequence the whole mammoth genome in the near future, possibly within the next year." 

The finding bears on the cultural fascination with re-creating extinct animals through cloning, but it hardly demonstrates its feasibility. "While we may now be able to retrieve the entire genome of the woolly mammoth, that does not mean we can put it together into organized chromosomes in a nuclear membrane with all the functional apparatuses needed for life. We can't even do that with modern DNA," Dr. MacPhee said. Most biologists will instead be more interested in comparing the new findings with the genetic sequences of living mammals and other animals to try and determine what led to the extinction of large mammals and other so-called megafauna. Complete genome sequences also allow biologists to study the molecular workings that lead to the genesis of new species and how genes evolve over time.

Dr. MacPhee's ongoing research involves looking for evidence of viruses that are widespread among mammals and for pathogens that might have affected mammoths and other megafauna and caused their extinction. If a virulent hyperdisease killed off all the mammoths, it is possible that scientists will find evidence of these pathogens in ancient DNA. 

For this new study of mammoths, Dr. MacPhee and his colleagues devised a novel approach to the commonly used DNA amplification technique called polymerase chain reaction (PCR) to attain the genomic results. PCR allows multiple rounds of amplification of a minimal amount of DNA material to obtain enough to arrive at longer and longer sequences of genetic code. DNA in the cell nucleus in every multicellular organism comes from both the subject's mother and father, and provides the organism's primary genetic material and blueprint for every body tissue and form. Once the mammoth DNA was extracted and amplified, the sequencing was completed in record time within hours by the latest in genomic research technologya new high-throughput machine, only two of which currently are in operation.

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