Gene hunting in hypoxia and exercise.

New technologies in genomics and proteomics are revolutionizing the study of adaptation to environmental stress. These approaches provide a comprehensive overview of the responses of thousands of genes/proteins to stress and enormously expand our view of the molecular and metabolic changes that underlie physiological responses. Several new technologies can help physiological labs to become gene hunters. DNA array screening is particularly effective for two purposes: (1) identifying coordinated responses by functional groups of gene/proteins such as multiple members of a signal transduction cascade or enzymes of a metabolic pathway, and (2) highlighting cell functions that have never before been linked with the stress under consideration. We have shown that heterologous screening of DNA arrays can be a highly effective method of gene hunting for the comparative biochemist provided that it is followed up by species-specific analyses including PCR to quantify transcript levels and Western blotting to analyze protein responses. Recent work in my lab has used cDNA array screening to evaluate responses to low oxygen by multiple hypoxia/anoxia tolerant systems, revealing common gene responses across phylogeny. Analysis of vertebrate facultative anaerobiosis in freshwater turtles reveals an interesting mixture of gene responses, including up-regulation of antioxidant enzymes, protease inhibitors, and proteins of iron metabolism; a few of these are coordinated by the hypoxia inducible factor in other systems but most are not. Array screening is also providing new insights into how exercise stimulates the growth of differentiated muscle cells and studies in our lab are identifying the gene responses associated with "anti-exercise"--gene up-regulation that aids hibernating mammals to maintain their muscle mass despite months of inactivity.