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: Devanand Sarkar, Rob Desalle, Paul B Fisher
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 105 Issue 44 Pg. 17040-5 (Nov 04 2008) ISSN: 1091-6490 [Electronic] United States
• PMID: 18971330 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CARD Signaling Adaptor Proteins
• DEAD-box RNA Helicases

Topics

• Animals
• CARD Signaling Adaptor Proteins (genetics)
• Cell Differentiation
• DEAD-box RNA Helicases (chemistry, classification, genetics)
• Evolution, Molecular
• Humans
• Immunity, Innate (genetics)
• Phylogeny
• Protein Structure, Tertiary
• Signal Transduction