Organismal, ecological, and evolutionary aspects of heat-shock proteins and the stress response: Established conclusions and unresolved issues

How heat-shock proteins function in diverse organisms from diverse environm ents, and how this diversification has evolved, is an emerging focus of res earch on molecular chaperones. As molecular chaperones, heat-shock proteins play diverse cellular roles, typically in minimizing dysfunction that may occur when other proteins are in non-native conformations. The standard asp ects of these roles in vitro, in isolated cells, and in typical model organ isms in the laboratory are now well-established, as are the ubiquity of hea t-shock proteins in organisms, the range of stresses that induce heat-shock proteins, the major families of heat-shock proteins, their expression in n ature, and their variation along natural gradients of stress. These aspects may no longer require extensive examination. By contrast, the frequency of natural expression of heat-shock proteins, their exact physiological roles in stress tolerance at levels of biological organization above the cell, t he exact molecular mechanisms by which heat-shock protein expression and fu nction has become tuned to the prevailing level of environmental stress, an d the fitness consequences of heat-shock protein expression in nature are a mong the numerous unresolved issues in this area.