June 17, 2008

A Step Back From Extinction

By Saey, Tina Hesman

Tasmanian tiger DNA turns on gene in mouse Tasmanian tigers are back. Sort of. A small bit of the extinct marsupial's DNA is alive and well in the cells of some genetically engineered mice.

Researchers have produced proteins from mammoth and Neandertal genes in cells. But the new study, published May 19 in PLoS ONE, is the first to show activity of an extinct piece of DNA in an animal.

Scientists from the University of Melbourne in Australia and the University of Texas M.D. Anderson Cancer Center in Houston extracted DNA from alcoholpreserved specimens of the Tasmanian tiger, or thylacine, extinct since 1936. The researchers then inserted into mice a piece of thylacine DNA that controls production of a collagen gene. The thylacine DNA worked, switching on a marker gene in cartilage-producing cells in a mouse embryo, essentially resurrecting a bit of the extinct animal.

But don't expect mice to transform into the doglike marsupials, or to see thylacines reanimated through cloning.

"This technology can tell us interesting things about thylacines bit by bit," says Robin Lovell-Badge, a developmental geneticist at the Medical Research Council's National Institute for Medical Research in Mill Hill, England. "As far as bringing back thylacines, this is not going to be able to do that."

But the researchers never intended to bring back the thylacine, just to learn something more about its biology and evolutionary history.

"We were very interested in finding out a little bit more about this iconic Australian carnivore, especially since we humans were responsible for its extinction," says biologist Marilyn Renfree of the University of Melbourne, one of the study's authors.

To prove that DNA from an extinct species can still work, the team chose a regulatory element, called an enhancer, which regulates the COL2A1 gene, says Andrew Pask, a molecular biologist at the University of Melbourne.

Enhancers serve as landing pads for proteins that turn genes on. Only specific proteins are granted landing privileges and only at prescribed times of development in particular cell types. The COL2A1 enhancer turns the gene on only in chondrocytes - cartilage- producing cells - in mouse embryos. The mouse embryos engineered with the thylacine enhancer turned on production of a marker that the researchers use to track gene activity. The enhancer worked only in chondrocytes.

The study is the first to use DNA from an extinct species to regulate gene activity. Previous studies used ancient DNA to encode proteins in cell cultures rather than in living animals.

"This is the next logical step to try to bring ancient DNA into an animal or biological system," says Stephan Schuster, a genomicist at Pennsylvania State University in University Park.

Researchers might use the technique to find regulatory elements that could make a chicken look like a dinosaur or an elephant look like a mammoth, he says. But such methods would not bring back dodos, dinosaurs and mammoths. "If you had a very hairy African elephant, that would be a first step to looking like a mammoth, but of course it wouldn't be a mammoth. It would just be a weird- looking elephant," Schuster says.

Even though the thylacine enhancer seems to work the same as the mouse enhancer, mice and marsupials are so different that sometimes enhancers in mice might misbehave, giving researchers the wrong impression about how such bits of DNA worked in the extinct animals, comments Carles Lalueza-Fox, a paleogeneticist at the University of Barcelona.

Tasmanien tigers, or thylacines (above), became extinct in 1936. Now scientists have inserted a piece of thylacine DNA into mice (an embryo shown at top), where It drives production of a marker gene (blue). The DNA turns on the marker in cells that produce cartilage.

Copyright Science Service, Incorporated Jun 7, 2008

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