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Amersham, San Diego Zoo Team up to Map Mammalian Family Tree

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Amersham Pharmacia Biotech and the San Diego Zoo said they are launching the first systematic effort to sequence DNA from representatives of all 146 mammalian families, a project that is expected to uncover previously unknown genetic relationships between mammals as well as lead to the development of a new sequencing platform.

Researchers will use existing bioinformatics packages like Consed, Sequencher, and Maximum to generate complete DNA sequences obtained from mammalian mitochondria, the cell’s extranuclear power-generating organelle.

But Amersham Pharmacia also plans to use the data set to test a new bioinformatics platform, said Robert Feldman, production sequencing and collaborations manager at Amersham.  The future platform will analyze sequence data from an evolutionary perspective, but Feldman said, “It’s too early to say much more.”

If the effort leads to new bioinformatics tools to help determine evolutionary relationships based on sequence data, as Amersham plans, this would be “a very interesting and important development,” said Mark Boguski, a founding member of the US National Center for Biotechnology Information. Researchers have been able to uncover evolutionary relationships from sequence data that they would not have discovered if they had only analyzed the organisms’ forms and structures, Boguski added.

The sequencing data, which will be provided by Amersham’s discovery lab in Sunnyvale, Calif., will be made freely available on GenBank and “all the usual sources,” Feldman said.

Feldman’s lab contains 15 MegaBACE 1000 DNA sequencing machines each capable of sequencing a half million base pairs a day. At 16,500 base pairs in each mitochondrial DNA, the sequencing could be done in a matter of days or weeks but getting and preparing the samples will slow the process. Feldman estimated that it would take about a year to complete the project.

Most of the tissue samples will come from San Diego’s Frozen Zoo, the world’s biggest genetic vault of DNA samples from endangered and rare species, such as the three-banded armadillo, the okapi giraffe, and the West African black rhino. But samples for some families—insectivores, for example—are extremely hard to obtain, said Feldman. His lab is currently waiting on a tissue sample from a rare spiny anteater to be shipped from the interior of China.

Researchers could look at the relationships between all these mammalian cousins by analyzing differences in their nuclear DNA, but the simpler mitochondrial DNA provides a shortcut. Researchers typically use mitochondrial DNA to shed light on evolutionary relationships since this extranuclear organelle is inherited only through the mother and mutates at a relatively constant rate. Thus, differences in mitochondrial DNA can point to how long ago one species broke off from another.

The data should help to fill some academic holes. Until now, research teams have only published a few papers on mitochondrial DNA sequences, one species at a time. “We’re really scaling things up,” Feldman said.

Geneticist Oliver Ryder at San Diego’s Zoological Society said the project would provide a scaffold on which other research teams will build. The project helps define “the whole-scale architecture of mammalian evolution,“ Ryder said.

But Boguski warned that biotech companies looking for animal models for human diseases will find no quick answers. His work in comparative genomics has taught him that disease models have to be found on a case-by-case basis. “We look more like worms in some cases and more like flies in others,” Boguski said.

—Melissa Mertl

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