On 2015 Jun 25, Donald Forsdyke commented:

In the light of new reviews (Zhang J, 2015 and Forsdyke DR, 2015), the following email to the senior author (May 27 2012) may be of interest:

'Thank you for a very interesting paper in PNAS Early Edition. The "potentially toxic" effect of protein-protein misinteractions forms the basis of our hypothesis of intracellular self/not-self discrimination, which is now receiving support from studies of the predisposition of females to autoimmune disease (J of Autoimmunity 38, J129-J134). Our earlier studies were influenced by the 1982 paper of E. H. McConkey on the "quinary structure" of proteins (PNAS 79, 3236-40). I have added a reference to your new paper as an "end-note" to the web version of a 2001 paper (see http://post.queensu.ca/~forsdyke/theorimm2.htm). I look forward to your future paper on the effect of interaction avoidance on the usage of synonymous codons.'

On 2013 Jul 11, Joshua L Cherry commented:

This article reports very interesting observations about the contributions of different types of sequence positions to the negative correlation between expression level and protein evolutionary rate (the E-R anticorrelation). However, the case for the assertion that is the title of the article is far from convincing. Much of the argument relies on predictions of protein stability made with I-Mutant2.0. The developers of that software report a correlation of only 0.62 between predicted and observed effects of mutations on stability (Capriotti E, 2005), and other assessments report even lower correlations (Potapov V, 2009). This would seem to leave much opportunity for incorrect classification of sequence positions as unimportant for stability. Furthermore, in seeking to explain their results the authors somewhat glibly discard the possibility of selection for protein function as a cause of E-R anticorrelation (in fact they seem to take it as established fact that toxic effects of misfolded proteins are a major, if incomplete, explanation). Surface residues are certainly involved in protein function, and selection for function should not be ruled out as an explanation of the negative correlation of their rate of evolution with expression level.

On 2013 Jul 11, Joshua L Cherry commented:

This article reports very interesting observations about the contributions of different types of sequence positions to the negative correlation between expression level and protein evolutionary rate (the E-R anticorrelation). However, the case for the assertion that is the title of the article is far from convincing. Much of the argument relies on predictions of protein stability made with I-Mutant2.0. The developers of that software report a correlation of only 0.62 between predicted and observed effects of mutations on stability (Capriotti E, 2005), and other assessments report even lower correlations (Potapov V, 2009). This would seem to leave much opportunity for incorrect classification of sequence positions as unimportant for stability. Furthermore, in seeking to explain their results the authors somewhat glibly discard the possibility of selection for protein function as a cause of E-R anticorrelation (in fact they seem to take it as established fact that toxic effects of misfolded proteins are a major, if incomplete, explanation). Surface residues are certainly involved in protein function, and selection for function should not be ruled out as an explanation of the negative correlation of their rate of evolution with expression level.

On 2015 Jun 25, Donald Forsdyke commented:

In the light of new reviews (Zhang J, 2015 and Forsdyke DR, 2015), the following email to the senior author (May 27 2012) may be of interest:

'Thank you for a very interesting paper in PNAS Early Edition. The "potentially toxic" effect of protein-protein misinteractions forms the basis of our hypothesis of intracellular self/not-self discrimination, which is now receiving support from studies of the predisposition of females to autoimmune disease (J of Autoimmunity 38, J129-J134). Our earlier studies were influenced by the 1982 paper of E. H. McConkey on the "quinary structure" of proteins (PNAS 79, 3236-40). I have added a reference to your new paper as an "end-note" to the web version of a 2001 paper (see http://post.queensu.ca/~forsdyke/theorimm2.htm). I look forward to your future paper on the effect of interaction avoidance on the usage of synonymous codons.'