Highly goes slowly

Rates of protein evolution vary widely. Very little of this variation is explained by dispensability (essential proteins evolving slowly), but up to a third is explained by expression levels. For an entirely mysterious reason, highly expressed proteins evolve slowly.Now, Allan Drummond and colleagues (Caltech, Pasadena, CA; and Keck Graduate Institute, Claremont, CA) argue that this correlation is based on the severe selective pressure on highly expressed proteins to avoid misfolding even when they are mistranslated. More abundant proteins are a greater misfolding threat because even a low misfolding rate would result in many misfolded, potentially toxic proteins—what Drummond calls “glue-covered monkey wrenches.” Genes encoding abundant proteins therefore get stuck, say the authors, in the few sequences that are “translationally robust”: they usually fold correctly even when there are translational errors.

The study...