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 (July 2 2012) may be of interest:

'Your fine new paper on dosage compensation in PNAS Early Edition links up nicely with your previous paper on protein misinteraction; that is, if you care to consider the hypothesis I advanced in 1994 (http://post.queensu.ca/~forsdyke/dominanc.htm), which is updated in my textbook (http://post.queensu.ca/~forsdyke/book05.htm). The basic point is that proteins have collective functions (such as the well-known Donnan equilibrium), as well as specific functions. Over evolutionary time protein concentrations have been fine-tuned to serve such collective functions. My 1994 paper postulated a novel collective function – aggregation pressure – through which an individual cell can initiate self/not-self discrimination. Each protein contributes to, and is acted upon by, this aggregation pressure. The more abundant a protein, the more it contributes and is acted upon.

Subsequent work on X chromosome dosage compensation has nicely supported this view ( http://post.queensu.ca/~forsdyke/theorimm7.htm). If a human female fails to compensate to some degree (both Xs expressed so aggregation pressure is high), then autoimmune disease is more likely. From the point of view of evolution, this would be a short-term effect and individuals would be negatively selected. On the other hand, if she were to excessively compensate (say part of a singly expressed X not expressed, so aggregation pressure is lowered), then she would stand an increased risk of getting infections. But since there are many alternatives for combatting infections, this would tend to be a long-term effect from the point of view of evolution. Thus, in your words “chromosome-wide expression halving has been tolerated” because “Y degeneration is stepwise” so that “expression reduction happened gradually to more and more X-linked genes during evolution.”'

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 (July 2 2012) may be of interest:

'Your fine new paper on dosage compensation in PNAS Early Edition links up nicely with your previous paper on protein misinteraction; that is, if you care to consider the hypothesis I advanced in 1994 (http://post.queensu.ca/~forsdyke/dominanc.htm), which is updated in my textbook (http://post.queensu.ca/~forsdyke/book05.htm). The basic point is that proteins have collective functions (such as the well-known Donnan equilibrium), as well as specific functions. Over evolutionary time protein concentrations have been fine-tuned to serve such collective functions. My 1994 paper postulated a novel collective function – aggregation pressure – through which an individual cell can initiate self/not-self discrimination. Each protein contributes to, and is acted upon by, this aggregation pressure. The more abundant a protein, the more it contributes and is acted upon.

Subsequent work on X chromosome dosage compensation has nicely supported this view ( http://post.queensu.ca/~forsdyke/theorimm7.htm). If a human female fails to compensate to some degree (both Xs expressed so aggregation pressure is high), then autoimmune disease is more likely. From the point of view of evolution, this would be a short-term effect and individuals would be negatively selected. On the other hand, if she were to excessively compensate (say part of a singly expressed X not expressed, so aggregation pressure is lowered), then she would stand an increased risk of getting infections. But since there are many alternatives for combatting infections, this would tend to be a long-term effect from the point of view of evolution. Thus, in your words “chromosome-wide expression halving has been tolerated” because “Y degeneration is stepwise” so that “expression reduction happened gradually to more and more X-linked genes during evolution.”'