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'Noisy' genes can have big impact

Experiments by Howard Hughes Medical Institute (HHMI) investigators have revealed how randomness in gene expression can have profound biological effects, both good and bad. The research in yeast helps explain how it might be possible for randomness in gene expression to lead to differences in cells -- or people for that matter -- that are genetically identical.

The researchers, HHMI investigator Erin K. O'Shea and colleague Jonathan M. Raser, both at the University of California, San Francisco, published their findings May 27, 2004, in Science Express, the online edition of the journal Science.

According to O'Shea, the original notion that random noise in gene expression -- the processes by which proteins are synthesized from the information contained in DNA -- arose from a paradox. "While processes such as gene expression involved in the development of organisms proceed in a very orderly fashion, paradoxically, they depend on chemical reactions that are inherently probabilistic, like flipping a coin," said O'Shea. "And since these processes involve small numbers of molecules, they should be significantly affected by chance, just as flipping a coin a few times will be more heavily affected than flipping it many times."

Earlier experiments by Michael Elowitz, who is now at the California Institute of Technology, and his colleagues at The Rockefeller University demonstrated that this type of random noise existed in the common bacterium E. coli. In later experiments, Raser and O'Shea set out to explore the mechanism underlying random noise in gene expression in a higher organism -- choosing the most primitive animal, yeast.

Raser and O'Shea used an indicator technique developed by Elowitz to detect noise in gene expression. They engineered yeast cells to produce blue and yellow fluorescent indicator proteins under the control of the same "promoter" -- the segment
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
27-May-2004


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