Method quickly surveys yeast genome by gene function, not sequence

Combining a decade of research advances, scientists have implemented a new method that essentially searches the entire yeast genome in an instant, looking for what the genes do rather than what they look like, say the researchers from Johns Hopkins and Rosetta Inpharmatics, Inc.

The scientists mixed more than 4,600 yeast mutants, each lacking a different gene, and put the pooled mutants in an environment that tested their ability to repair DNA. They were then able to sort out how each mutant performed by using microarray technology, according to the report in the Dec. 21 issue of the journal Science.

Amounting to a "functional" microarray, these experimental steps marry classical genetics, which was used initially to identify many of the genes, with high-tech genomics, whose goal is determining the function of genes, say the researchers.

"The sequence of the yeast genome is available and the human genome is in draft form, so now there's a big push to figure out what the genes do," says Jef Boeke, Ph.D., D.Sc., professor of molecular biology and genetics at Johns Hopkins. "We tested DNA repairing ability, but we can use this method to identify genes involved in many other cellular processes. It should dramatically speed our efforts to understand genes' functions."

Some 6,000 yeast genes are known, and a mutant strain for each one was made thanks to an international effort, including major contributions from Boeke's lab (pronounced BU-ka). It isn't difficult to see whether a mutant can last in a given environment, which is how scientists evaluate the missing gene's function, but until now, each mutant had to be tested separately.

Testing all 4,600-plus existing mutants at the same time depends on a "barcode" system developed by Dan Shoemaker of Rosetta Inpharmatics, Inc., that identifies the mutants as easily as the varying stripes of a UPC symbol di

Contact: Joanna Downer
Johns Hopkins Medical Institutions

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