TO AN engineer, biological systems can look horribly sloppy. But when it comes to gene activity, a little sloppiness can be the key to survival.
Gene expression is a surprisingly 鈥渘oisy鈥 or variable process: even in a group of seemingly identical cells, there is often huge variation in the activity of a given gene from cell to cell. In recent years, some theorists have used computational models to suggest that this noise helps organisms cope better with environmental stresses, but until now there has been little experimental evidence to back this up.
To fill that gap, researchers led by Jim Collins of Boston University took yeast and mutated a naturally noisy promoter sequence that controls the activity of a particular gene. By also tweaking the culture conditions, they created populations of engineered yeast cells in which the gene controlled by the promoter had the same average activity, but differed in its noise level. While the unmodified promoter caused bursts of activity in the gene, the mutated versions gave a slower, steadier response.
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Next the researchers linked the natural and mutated promoters to an antibiotic resistance gene and inserted them into yeast cells. When they exposed the cells to the antibiotic, only cultures with the noisy unmodified promoter were able to grow (Molecular Cell, vol 24, p 853). They believe some cells in these cultures were able to overcome the antibiotic鈥檚 effects thanks to sudden spurts of gene expression.
Adam Arkin, a systems biologist at the University of California, Berkeley, is impressed with Collins鈥檚 findings. 鈥淗e takes a real engineering approach,鈥 says Arkin. Collins concedes that some biologists may question whether his engineered yeast cells are relevant to the natural situation, but he points out that the noisy promoters like the one he studied control genes that help yeast cells respond to environmental stresses. 鈥淥ur underlying point is reflected in the natural genome,鈥 he says.