3 June 2011
Allan Drummond
FAS Centre for Systems Biology
Harvard University
The conversion of genetic information into phenotypic information by transcription and translation is 100,000 times more error-prone than DNA replication. At the canonical rate of one error for every 2000 codons translated, 20% of typical-length proteins will contain errors. Single amino-acid changes can disrupt protein folding, leading to the hypothesis that natural selection will act to reduce the costs of error-induced protein misfolding. It has long been known that misfolded proteins provoke a heat-shock-like response when present at high levels even at normal temperatures (such as following drug treatment that produces widespread misfolding). Our experiments reveal that budding yeast is sensitive to protein misfolding present at far lower levels than previously studied; yeast cells slow growth and mount a targeted chaperone response in the cytosol when misfolded protein represents less than 0.1% of total protein. What does this mean for the architecture of the quality control system, and for the distribution of selective pressures against misfolding across the proteome?