(mammoth) Royal British Columbia Museum; (inset) Joerg Stetefeld

Defrosted. Woolly mammoth hemoglobin contains unique regions (blue) that interact with other regions (red) to deliver oxygen at a steady rate regardless of temperature.

Scientists Resurrect Mammoth Hemoglobin

By inserting a 43,000-year-old woolly mammoth gene into Escherichia coli bacteria, scientists have figured out how these ancient beasts adapted to the subzero temperatures of prehistoric Siberia and North America. The gene, which codes for the oxygen-transporting protein hemoglobin, allowed the animals to keep their tissues supplied with oxygen even at very low temperatures. "It's no different from going back 40,000 years and taking a blood sample from a living mammoth," says Kevin Campbell, a biologist at the University of Manitoba in Canada.

Campbell's team obtained DNA from mammoth bone preserved in the Siberian permafrost. It was a long journey for Campbell, whose specialty is the physiology of mammals. A decade ago, he saw a Discovery Channel program on the recovery of a mammoth specimen encased in ice and wondered if such specimens might hold clues to the physiology of the mammoth.

Campbell worked with DNA expert Alan Cooper of the University of Adelaide in Australia to isolate the mammoth gene responsible for hemoglobin. Then, he and colleagues plugged the gene into E. coli. The goal, says Campbell, was to make the bacteria produce mammoth hemoglobin in the lab. (A similar process is used to synthesize human proteins like insulin.) Although they were created in a bacterium, he says, the hemoglobin proteins are identical to what mammoth cells would have produced. "I figured if E. coli can make perfect human hemoglobin, why can't it make mammoth hemoglobin?"

Once the researchers had their mammoth hemoglobin, they compared it with that from Asian and African elephants (also created in the lab using genes from living animals spliced into E. coli). The elephant hemoglobin functioned much like human hemoglobin, delivering oxygen more efficiently at warmer temperatures. That helps the hemoglobin transport oxygen to the hardest-working muscles. But the mammoth hemoglobin released oxygen at a steady rate regardless of the temperature, the team reports online today in Nature Genetics.

Those differences help explain how the mammoth was able to adapt to frigid temperatures as it evolved from its elephantlike African ancestor over tens of millions of years. In addition to tiny ears and thick wool, Campbell suggests that mammoths may have developed ways to let their limbs and extremities cool dramatically to save energy and conserve their body's core temperature, a physiological trick used by cold-adapted modern animals such as reindeer and muskoxen. But cold feet present a problem when it comes to hemoglobin. "What the mammoth evolved is changes in hemoglobin that reduce the amount of heat needed to exchange oxygen," Campbell says, which allowed the animals to keep their extremities "breathing" even at very low temperatures.

Mammoth expert Ralf-Dietrich Kahlke of the Senckenberg Research Institute in Weimar, Germany, says the result jibes with what is known about the timing and trends of mammoth evolution, and it represents an impressive step beyond what ancient DNA has been able to do so far. "It's good to get the ancestry and evolution of the animals with ancient DNA, but for me it's much more exciting that we get results to understand the stamina and power of the animals," Kahlke says. "This is sort of the first result in paleophysiology."

Biologist Michael Berenbrink of the University of Liverpool in the United Kingdom says more research is needed to see how significant the adaptation was, however. There's a possibility, for example, that cold tissue needs less oxygen to begin with. "They take it for granted that they have this problem of delivering oxygen," Berenbrink says. Still, he says, the work is a "fantastic" combination of existing methods to answer a new question. "The extraordinary thing is to get the sequence out of an extinct animal, express the protein, and come up with an explanation of its adaptive function."

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Posted in Evolution, Biology, Environment