UC San Diego

Various lipophilic signals, including ecdysone, retinoic acid, estradiol, cortisol, testosterone and progesterone, act through nuclear receptors, a large group of transcription factors that regulate differentiation and development, which are central to metamorphosis. Here, we focus on environmental factors (e.g. climate, chemicals) in the evolution of nuclear receptors and other signal transduction proteins that interact with heat shock protein 90 (Hsp90), a chaperone that promotes the proper folding and trafficking in cells of proteins. Hsp90 also promotes functional folding of some mutant signal proteins, which would be otherwise destabilized. Stress diverts Hsp90 from stabilizing mutant signal transduction proteins and towards promoting proper folding of stress-damaged proteins and preventing the aggregation of denatured proteins. Reduced Hsp90 levels allow expression of cryptic mutations in signal transduction proteins and new developmental patterns. Thus, environmental stress in the form of extreme climate can influence the evolution of metamorphosis. We discuss how extreme cooling called “Snowball Earth”, which occurred in the late Proterozoic, diverted Hsp90 from chaperoning signal-transduction proteins. As a result, pre-existing mutant signal transduction-proteins were expressed in animals. Some mutations were selectively advantageous in animals that are seen in the Cambrian, when diverse pathways for metamorphosis in metazoans first appear in the fossil record. Other environmental factors, such as biological chemicals (e.g. the antibiotic geldanamycin) can reduce the levels of active HSP90 providing another mechanism for the emergence of mutant signaling pathways.