title: Phenotypic spandrel: absolute discrimination and ligand antagonism.
abstract: We consider the general problem of sensitive and specific discrimination between biochemical species. An important instance is immune discrimination between self and not-self, where it is also observed experimentally that ligands just below the discrimination threshold negatively impact response, a phenomenon called antagonism. We characterize mathematically the generic properties of such discrimination, first relating it to biochemical adaptation. Then, based on basic biochemical rules, we establish that, surprisingly, antagonism is a generic consequence of any strictly specific discrimination made independently from ligand concentration. Thus antagonism constitutes a 'phenotypic spandrel': a phenotype existing as a necessary by-product of another phenotype. We exhibit a simple analytic model of discrimination displaying antagonism, where antagonism strength is linear in distance from the detection threshold. This contrasts with traditional proofreading based models where antagonism vanishes far from threshold and thus displays an inverted hierarchy of antagonism compared to simpler models. The phenotypic spandrel studied here is expected to structure many decision pathways such as immune detection mediated by TCRs and FCϵRIs, as well as endocrine signalling/disruption.
authors.forename: Paul
authors.initials: P
authors.lastname: François
authors.forename: Mathieu
authors.initials: M
authors.lastname: Hemery
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Johnson
authors.forename: Laura N
authors.initials: LN
authors.lastname: Saunders
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D008962:Models, Theoretical; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*
chemical_list: D008024:Ligands; D011948:Receptors, Antigen, T-Cell