title: Which came first, the lectin/classical pathway or the alternative pathway of complement?
abstract: It is a widely accepted canon of immunology that the alternative pathway is more primitive and hence older in evolutionary terms than the lectin/classical pathway. This idea has been reinforced by the discovery of "C3" and "factor B" proteins in invertebrate species. However, it is clear that the gene duplications which gave rise to C3/C4/C5 and factor B/C2 occurred in the vertebrate lineage. Hence, the naming of the invertebrate proteins may be based on preconceptions rather than on solid structural or functional evidence. Lectins and associated MASP/C1r/C1s-like proteins have been found in invertebrates, while factor D, the defining component of an alternative pathway, has so far been found only in the bony fish and higher species. It is a principle of Darwinian evolution that complex systems develop through small sequential steps. It is possible to imagine such a series of steps for the evolution of a lectin pathway, involving as it does recognition of non-self. It is difficult to see how the alternative pathway, which lacks a recognition molecule, could have evolved without the prior development of control proteins to protect self from attack.
authors.affiliation: Department of Biochemistry, University of Oxford, UK. al@bioch.ox.ac.uk
authors.forename: Alister W
authors.initials: AW
authors.lastname: Dodds
mesh_terms: D000818:Animals; D003170:Complement Pathway, Alternative / Q000235:genetics*; D003171:Complement Pathway, Classical / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D037102:Lectins / Q000276:immunology*; D010802:Phylogeny
chemical_list: D037102:Lectins