title: Evolution of MDA-5/RIG-I-dependent innate immunity: independent evolution by domain grafting.
abstract: Type I Interferons (IFNs) are requisite components in antiviral innate immunity. Classically, a Toll-like receptor-dependent pathway induces type I interferons. However, recent recognition of melanoma differentiation associated gene-5 (MDA-5) and retinoic acid inducible gene-I (RIG-I) as primary sensors of RNA viruses for type I interferon induction highlights a potentially unique pathway for innate immunity. Our present investigation tracing the phylogenetic origin of MDA-5 and RIG-I domain arrangement (CARD1-CARD2-helicase-DEAD/DEAH) indicates that these proteins originated specifically in mammals, firmly linking this family of proteins with interferons in a highly derived evolutionary development of innate immunity. MDA-5, but not RIG-I, orthologs are found in fish, indicating that MDA-5 might have evolved before RIG-I. Our analyses also reveal that the MDA-5 and RIG-I domain arrangement evolved independently by domain grafting and not by a simple gene-duplication event of the entire four-domain arrangement, which may have been initiated by differential sensitivity of these proteins to viral infection.
authors.affiliation: Department of Human and Molecular Genetics, Institute of Molecular Medicine, Massey Cancer Center, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA. dsarkar@vcu.edu
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
authors.forename: Rob
authors.initials: R
authors.lastname: Desalle
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics; D002454:Cell Differentiation; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
chemical_list: D053468:CARD Signaling Adaptor Proteins; D053487:DEAD-box RNA Helicases