Recent works in quantitative evolution have shown that biological structures are constrained by selected phenotypes in unexpected ways . This is also observed in simulations of gene network evolution, where complex realistic traits naturally appear even if they have not been explicitly selected . An important biological example is the absolute discrimination between different ligand "qualities", such as immune decisions based on binding times to T cell receptors (TCRs) or Fc%DIFDELCMD < \epsilonRIs%%% . In evolutionary simulations, the phenomenon of absolute discrimination is not achieved without detrimental ligand antagonism : a "dog in the manger" effect in which ligands unable to trigger response prevent agonists to do so. A priori it seems paradoxical to improve ligand discrimination in a context of increased ligand antagonism, and how such contradictory phenotypes can be disentangled is unclear. Here we establish for the first time a direct mathematical causal link between absolute discriminationand ligand antagonism.Inspired by the famous discussion by Gould and Lewontin, we thus qualify antagonism as a  "phenotypic spandrel": a phenotype existing as a necessary by-product of another phenotype. We exhibit a general model for absolute discrimination , and further show how addition of proofreading steps inverts the expected hierarchy of antagonism without fully cancelling it. Phenotypic spandrels reveal the internal feedbacks and constraints structuring response in signalling pathways, in very similar way to symmetries structuring physical laws\epsilonRIs .
%DIFDELCMD < \epsilonRIs%%% We consider the general problem of absolute discrimination between categories of ligands irrespective of their concentration. An instance of this problem is immune discrimination between self and not-self. We connect this problem to biochemical adaptation, and establish that ligand antagonism - the ability of sub threshold ligands to negatively impact response - is a necessary consequence of absolute discrimination.Thus antagonism constitutes a "phenotypic spandrel": a phenotype existing as a necessary by-product of another phenotype. We exhibit a simple analytic model of absolute discrimination displaying ligand antagonism, where antagonism strength is linear in distance from threshold. This contrasts with proofreading based models, where antagonism vanishes far from threshold and thus displays an inverted hierarchy of antagonism compared to simple model . The phenotypic spandrel studied here is expected to structure many decision pathways such as immune detection mediated by TCRs and Fc\epsilonRIs .
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Recent works in quantitative evolution have shown that biological structures are constrained by selected phenotypes in unexpected ways . This is also observed in simulations of gene network evolution, where complex realistic traits naturally appear even if they have not been explicitly selected . An important biological example is the absolute discrimination between different ligand "qualities", such as immune decisions based on binding times to T cell receptors (TCRs) or Fc
R
. In evolutionary simulations, the phenomenon of absolute discrimination is not achieved without detrimental ligand antagonism : a "dog in the manger" effect in which ligands unable to trigger response prevent agonists to do so. A priori it seems paradoxical to improve ligand discrimination in a context of increased ligand antagonism, and how such contradictory phenotypes can be disentangled is unclear. Here we establish for the first time a direct mathematical causal link between absolute discriminationand ligand antagonism.Inspired by the famous discussion by Gould and Lewontin, we thus qualify antagonism as
We consider the general problem of absolute discrimination between categories of ligands irrespective of their concentration. An instance of this problem is immune discrimination between self and not-self. We connect this problem to biochemical adaptation, and establish that ligand antagonism - the ability of sub threshold ligands to negatively impact response - is
A
necessary consequence of absolute discrimination.Thus antagonism constitutes a
R
general model for absolute discrimination , and further show how addition of proofreading steps inverts the expected
simple analytic model of absolute discrimination displaying ligand antagonism, where antagonism strength is linear in distance from threshold. This contrasts with proofreading based models, where antagonism vanishes far from threshold and thus displays an inverted
R
without fully cancelling it. Phenotypic spandrels reveal the internal feedbacks and constraints structuring response in signalling pathways, in very similar way to symmetries structuring physical laws
compared to simple model . The phenotypic spandrel studied here is expected to structure many decision pathways such as immune detection mediated by TCRs and Fc