The mammalian complement system as an epitome of host-pathogen genetic conflicts

Rachele Cagliani, Diego Forni, Giulia Filippi, Alessandra Mozzi, L. De Gioia, Chiara Pontremoli, Uberto Pozzoli, Nereo Bresolin, Mario Salvatore Clerici, Manuela Sironi

Research output: Contribution to journalArticlepeer-review


The complement system is an innate immunity effector mechanism; its action is antagonized by a wide array of pathogens and complement evasion determines the virulence of several infections. We investigated the evolutionary history of the complement system and of bacterial-encoded complement-interacting proteins. Complement components targeted by several pathogens evolved under strong selective pressure in primates, with selection acting on residues at the contact interface with microbial/viral proteins. Positively selected sites in CFH and C4BPA account for the human specificity of gonococcal infection. Bacterial interactors, evolved adaptively as well, with selected sites located at interaction surfaces with primate complement proteins. These results epitomize the expectation under a genetic conflict scenario whereby the host's and the pathogen's genes evolve within binding avoidance-binding seeking dynamics. In silico mutagenesis and protein-protein docking analyses supported this by showing that positively selected sites, both in the host's and in the pathogen's interacting partner, modulate binding.

Original languageEnglish
Pages (from-to)1324-1339
Number of pages16
JournalMolecular Ecology
Issue number6
Publication statusPublished - Mar 1 2016


  • complement system
  • host-pathogen genetic conflict
  • human-specific infections
  • positive selection

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics


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