Journal Watch: MHC and intracellular self

Mon Aug 24 08:18:33 EST 1992

>>Continuing the discussion on intracellular self/not-self discrimination....
>>  Forsdyke:      So, the next question I offer is: What evolutionary forces,
>>              acting by modifying the gene sequence, mould the encoded life-
>>              span of a particular gene product?
>   Prasad:
>For some proteins for which a long half-life is necessary, evolution may have
>selected for mutations that increased stability without severely affecting
>function.  Other ways that protein stability is increased are:
>        1.  Compartmentalization - sequestering that protein away from
>                proteases.
>        2.  Forming complexes - such as ribosomal proteins with rRNA, and
>                protein-protein complexes.
>        3.  Modification - (hand-waving on my part) phosphorylation,
>                glycosylation, or other additions may increase stability.
>                On the other hand, some modifications may "mark" proteins
>                for degradation (and the resulting peptides would be presented
>                by MHC...).
   Forsdyke: So, we agree that parts of the gene, both the protein-
             encoding part and other parts, can be acted upon by
             evolutionary forces to affect (i) specific function, (ii) quant-
             ity, and (iii) distribution (compartments or complexes) of the
             gene product (protein). [The ability to be modified is also a
             function of the protein sequence and this may affect (i) to (iii)]
                For simplicity, as in our initial test-tube model, we can
             consider (i) and (ii) in relationship to the cytosolic compartment
             The evolution of specific function and protein concentration can
             be considered independently. The protein has a theoretically
             possible maximum specific activity (activity/unit protein). There
             is a minimal level of activity needed by the cell. So this sets
             the lower limit on protein quantity. As this quantity rises above
             this lower limit the specific activity can decrease and still
             maintain the same level of function. So gene is free to respond to
             evolutionary forces affecting protein quantity, without compromis-
             ing function. Do you accept all this? 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?
                   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, 858 edt
>                     Prasad, S. (1992) Bionet.immunology 821, 1544gmt

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