Abstract
The crowded cytosol is a special environment where weak interactions can be important. Here many macromolecules are close to the limits of their solubility, a condition conducive to weak, but specific, entropy-driven molecular interactions. In addition to being under evolutionary constraint to preserve the functions of their own products, genes encoding specific cytosolic proteins are also under evolutionary constraint, both to support a pressure exerted collectively by proteins to drive other proteins from solution, and to maintain the solubilities of their own proteins in the face of that collective pressure. Thus, genes whose protein products occupy a common cytosol have co-evolved such that product concentrations are fine-tuned to a maximum consistent with avoiding self-aggregation. Cytosolic proteins collectively generate a pressure tending to drive proteins into aggregates. Each individual diffusible protein species both contributes to, and is influenced by, the pressure. Intracellular pathogens must fine-tune the concentrations of their own proteins to the solubility limits so imposed. Aggregates between viral proteins and normal host, antibody-like, ‘immune receptor’ proteins, provide a possible basis for intracellular self/not-self discrimination at the protein level. Molecular chaperones, including heat-shock proteins, modulate this process. In such terms, we can explain Goldschmidt ’s phenocopy phenomenon, and paraneoplastic diseases. During their development there is positive selection of host lymphocytes reactive with near-self antigens (positive repertoire selection). This counters the tendency of pathogens to mutate towards self. Thus, hosts whose immunological forces are poised to attack near-self versions of not-self (a subset of not-self), rather than not-self per se (the entire set of not-self – formidable in range), are at a selective advantage.
If you can talk with crowds and keep your virtue,
Or walk with Kings – nor lose the common touch,
Yours is the Earth and everything that’s in it.”
Rudyard Kipling [1]
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Forsdyke, D.R. (2016). The Crowded Cytosol. In: Evolutionary Bioinformatics. Springer, Cham. https://doi.org/10.1007/978-3-319-28755-3_16
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DOI: https://doi.org/10.1007/978-3-319-28755-3_16
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