Key players among the cell's stress management consultants, some heat shock proteins may spend their down time preventing mutations from turning into physical deformities. A study of fruit flies, reported in tomorrow's Nature, suggests that these silenced mutations--and perhaps helpful ones, too--may surface when one particular heat shock protein is itself mutated or must cope with potentially damaging heat or cold.
Like other heat shock proteins, HSP90 helps other proteins fold into the proper shape to function well. HSP90 works with many of the proteins that guide development, keeping them poised to respond to growth-stimulating messages, for example. HSP90 also lends a hand when stressful conditions threaten to unravel these proteins. Suzanne Rutherford and Susan Lindquist, cell biologists at the University of Chicago, became curious about the role HSP90 might play in evolution when they noticed that about 2% of fruit flies with a mutated HSP90 gene had misshapen wings or legs, abnormal eyes or bristles, or other odd physical flaws. Perhaps, they mused, faulty HSP90 genes might allow existing mutations to wreak havoc.
Breeding experiments tied the deformities to mutations in several genes, but a faulty heat shock protein itself was not responsible for any single problem. However, when the researchers fed young fruit flies a substance that stifled heat shock protein activity, about 8% more flies were deformed as adults than were those on a normal diet. The same proved true when the fruit flies were raised in unusually high or low temperatures, 30° or 18°C--conditions that jack up the stress-reduction activity of HSP90.
Rutherford and Lindquist think that under normal conditions, HSP90 compensates for small genetic glitches that would otherwise alter the stability and function of the proteins used to build the fly. As a result, mutations can accumulate without any apparent effect. "It's the first molecular mechanism [found] for allowing an organism to store up genetic variation," Lindquist says. But if HSP90 itself is abnormal, or if the supply of HSP90 is being exhausted to deal with stresses, then developmental proteins are on their own, and the consequences--either good or bad--of those mutations become apparent.
The finding could help explain how some organisms can cope with changing environments. By harboring a reservoir of mutations, HSP90 "gives [the organism] the capacity to evolve rapidly," comments Marc Kirschner, a cell biologist at Harvard University. At the same time, it shows how these organisms, under normal conditions, are buffered against what otherwise might be detrimental mutations.