title: Fc receptors for immunoglobulins and their appearance during vertebrate evolution.
abstract: Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR γ chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Uppsala, Sweden.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Akula
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Uppsala, Sweden.
authors.forename: Sayran
authors.initials: S
authors.lastname: Mohammadamin
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Hellman
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D023281:Genomics; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011961:Receptors, Fc / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014714:Vertebrates
chemical_list: D007136:Immunoglobulins; D011961:Receptors, Fc