Considering the fine-tuning of protein concentration as a proposed mechanism
of intracellular self/not-self discimination:
In article <robison1.714747862 at husc10>, robison1 at husc10.harvard.edu (Keith
Robison) says:
> I would like to point out the following paper (just published):
>> Berg, O.G. 1992. PNAS 89:7501-7505
> The evolutionary selection of DNA base-pairs in gene-regulatory
> binding sites.
>>"The DNA base-pair sequences that serve as gene-regulatory sites have been
>selected to provide an appropriate functional binding for a particular
>protein. In most cases, the function depends on the binding
>probability, which can be influenced both by the binding strength
>and by the abundance of the protein in the cell. As a consequence,
>the same function can be achieved with strong binding sites and
>a small amount of protein or weak binding sites and a strong
>amount of protein. However, increasing the protein burden will
>decrease the growth rate of the cells. Thus, for maximal growth
>the protein levels should be as low as possible and the binding
>correspondingly strong. On the other hand, sequences with a
>weaker binding can be formed in many more ways and are, therefore,
>more probable, and random mutations are more likely to produce them.
>Thus the selection pressure against an increased protein burden
>can be balanced against the random mutational drift in the recognition
>sequences...
>Keith Robison
Forsdyke: Proteins have to be made and degraded and this imposes a "burden"
in metabolic terms. The less synthesis and the less degradation
that is going on, the less will be the burden. The final quantity
of protein within a cell is the result of a balance between these
two. If it wants to increase the quantity of a protein it can
either increase the synthesis rate (burden up), or decrease the
degradation rate (burden down). Thus the final protein quantity
arrived at can be independent of net metabolic burden.
Even if "burden" were one of the factors affecting the
evolution of protein quantity within cells, the ability to
discriminate self from not-self intracellularly would, in my
opinion,constitute a more powerful evolutionary selective force.
Sincerely, Don Forsdyke
References:
Robison, K. (1992) Bionet.immunology 825, 1304gmt
