"Drips" -- Susan S. Roberts
“Drips” (Susan S. Roberts. 2007)

A while ago, I posted a brief extract from a 2008 paper from Drummond & Wilke1 that determined that 18% of proteins have at least one misincorporated amino acid, and linked that to my commentary on Yewdell’s “DRiPs” hypothesis here (also see here for more commentary).  At the time, I took the 18% figure as surprisingly good support for Yewdell’s notion that a large fraction of proteins are misfolded (and therefore rapidly degraded) on translation.

Claus Wilke just gave a really interesting seminar here and I had a chance to chat with him about this paper and much more, so I want to clarify that he does not take this finding as support for (or disproof of) the DRiPs hypothesis.  Claus’s point, supported more strongly in subsequent papers,2 is that proteins incorporate this level of aberrant amino acids without experiencing misfolding as a consequence.  He argues that genes have evolved enough robustness in their folding parameters that they can and do tolerate this level of mistranslation.  Since Yewdell’s hypothesis is based on mis-folding, I think Claus’s data are more or less neutral with regard to DRiPs.

  1. Mistranslation-Induced Protein Misfolding as a Dominant Constraint on Coding-Sequence Evolution. D. Allan Drummond and Claus O. Wilke. Cell 134:341-352 (25 July 2008) doi:10.1016/j.cell.2008.05.042[]
  2. For example:  The evolutionary consequences of erroneous protein synthesis. D. Allan Drummond & Claus O. Wilke.  Nature Reviews Genetics 10, 715-724 (October 2009) doi:10.1038/nrg2662[]