Journal Watch: MHC and intracellular self

Mon Aug 24 14:16:15 EST 1992

>> Forsdyke:   The evolution of specific function and protein concentration can
>>             be considered independently. The protein has a theoretically
>>             possible maximum specific activity (activity/unit protein).
               ..................................... If so, would you care to
>>             speculate what evolutionary forces would determine that a
>>             particular gene evolve to set a particular protein concentration
>>             within a particular cytosol?
>> Prasad:
>I just bought a copy of "The Selfish Gene" this weekend, and haven't had the
>time to read it yet (yes, I know I should have read it years ago).  Maybe the
>answers to everything are written within.
>The cytosolic concentration of a protein would be determined (teleologically
>speaking) by necessity.  For example, organisms in a certain environment would
>need certain proteins more that organisms in other environments, e.g. DNA-
>repair proteins may be in higher concentration in bacteria exposed to high
>UV rays, or other radiation than in the average lab strain of E. coli.
>could be as simple as selection for those that express the appropriate level
>of that protein to survive.  Let's take UV rays as a speculative example.
>Normally they would damage DNA, but the one-cell-in-a-billion whose
>exposure to UV leads to an up-promoter mutation in the DNA repair operon
>would have a selective advantage over the others, and may eventually survive,

  Forsdyke: When you talk about uv-inducible protein, as example, you are
            still thinking in terms of specific protein FUNCTION. I invite
            you to think in terms of proteins as proteins. They have properties
            as such. For example, they would have some osmotic effect if on
            one side of a semi-permeable membrane. I seem to recall that
            the collective functions of proteins are invoked by the
            physiologists to explain Donnan equilibrium. Now, if these
            collective functions were important from the viewpoint of
            evolutionary selection, then genes would be modified based on
            selection for these functions.
              Turning back to the test-tube model, one collective function
            is the pressure exerted by proteins on each other. That was why in
            my original model I asked you to consider the effect of collective-
            ly increasing protein concentration on the aggregation of
            individual proteins. A given protein, both contributes to the
            pressure to drive proteins from solution, and is acted upon by that
              Now to introduce a Dawkins note, but in our context we are
            talking about "self" genes, which, like "not-self" genes, are also
            "selfish". Self genes jump aboard the chromosome and travel
            together into the next generation. They adapt to each other and
            thus begin to define "self". The particular property of interest
            is that of protein concentration. Throughout evolutionary time
            each gene "fine-tunes" its protein concentration to the collective
            pressure exerted by the other proteins with which it is moving
            through time. At the same time, all the proteins tend to maximize
            the collective pressure to drive individual proteins from solution,
            by pushing their own concentrations to the limit.  In this
            cytosolic environment, a not-self protein might more readily
            exceed its individual solubility limits. Thus is would aggregate
            and mark itself as foreign, thus fulfilling the criterion
            advanced earlier for its being conducted, via proteosomes, to the
            MHC protein complexes.
               This is not the end of the story. There are some flaws to this
            argument. Perhaps you can spot them, and others that I have not
               Sincerely,  Don Forsdyke
>>>>>>>>>>References:   Forsdyke, D. (1992) Bionet.immunology 812 947edt
>>>>>>>>>>              Prasad, S. (1992) Bionet.immunology 814 1516gmt
>>>>>>>>>>              Forsdyke, D. (1992) Bionet.immunology 817 1757edt
>>>>>>>>>>              Prasad, S. (1992) Bionet.immunology 818 133gmt
>>>>>>>>>               Forsdyke, D. (1992) Bionet.immunology 818, 1616edt
>>>>>>>>                Prasad, S. (1992) Bionet.immunology 819, 405gmt
>>>>>>>                 Forsdyke, D. (1992) Bionet.immunology 819 1019edt
>>>>>>>                 Prasad, S. (1992) Bionet.immunology 819, 2019gmt
>>>>>                   Forsdyke, D. (1992) Bionet.immunology 820, 858edt
>>>>>>                  Prasad, S. (1992) Bionet.immunology 821, 56gmt
>>>                     Forsdyke, D. (1992) Bionet.immunology, 821, 858edt
>>>                     Prasad, S. (1992) Bionet.immunology 821, 1544gmt
>                       Forsdyke, D. (1922) Bionet.immunology 824, 918edt
>                       Prasad, S. (1992) Bionet.immunology 824, 1814gmt

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