( ant genes on the cells' viability. Sinc...)Technique offers new view of dynamic biological landscape

ant genes on the cells' viability. Since yeast form round colonies when grown in culture dishes, they could measure the mutant cells' colony size in an automated fashion and use that to calculate their growth rates. To determine epistatic effects, they compared the growth rate for each cell containing mutations in two genes with the growth rate of mutant cells carrying mutations in only one of those genes.

"The analysis of these epistatic interactions gave us a unique and coherent perspective on the function and structure of this network in yeast," Weissman explained. "And it also proved a great way to find new gene functions or to figure out how known genes were functioning and the processes they were likely to be involved in. But on top of that, we could identify groups of genes that were acting in a coherent way, to produce protein complexes. And then on a more global level, we could see how the different processes were interacting with each other.

"By contrast, in classical genetics, you begin with a process you're interested in -- for example secretion -- and look for all the genes that affect secretion. It's a productive approach, but it's very process oriented," he said. "You might find a given gene that's involved in secretion, but it doesn't tell you about the many other processes it could be involved in.

With the E-MAP approach, however, the researchers start with the gene and ask about all the processes that it affects. "It gives you a less hypothesis-biased, more objective way of looking at the structure of biological systems," Weissman said.

In future studies, Weissman and his colleagues plan to develop better quantitative measures of the effects of epistatic interactions and to extend their technique to other organisms, ultimately to humans.

In addition to offering important basic insights into the roles of proteins and genes, E-MAPs will also contribute to understanding evolutionary processes. "In evolution
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Source:Howard Hughes Medical Institute

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