tetano
Editor, Senior Moderator
J Mol Biol. 2013 Nov 6. pii: S0022-2836(13)00698-0. doi: 10.1016/j.jmb.2013.10.040. [Epub ahead of print]
RIG-1-like receptors evolved adaptively in mammals, with parallel evolution at LGP2 and RIG-I.
Cagliani R, Forni D, Tresoldi C, Pozzoli U, Filippi G, Rainone V, De Gioia L, Clerici M, Sironi M.
Source
Scientific Institute IRCCS E. Medea, 23842 Bosisio Parini (LC), Italy.
Abstract
RIG-I-like receptors (RLRs) are nucleic acid sensors that activate antiviral innate immune response. These molecules recognize diverse non-self RNA substrates and are antagonized by several viral inhibitors. We performed an evolutionary analysis of RLR genes (RIG-I, MDA5, and LGP2) in mammals. Results indicated that purifying selection had a dominant role in driving the evolution of RLRs. However, application of maximum-likelihood analyses identified several positions that evolved adaptively. Positively selected sites are located in all domains of MDA5 and RIG-I, whereas in LGP2 they are confined to the helicase domain. In both MDA5 and RIG-I, the linkers separating the CARD and helicase domains represented preferential targets of positive selection. Independent selective events in RIG-I and LGP2 targeted the corresponding site (Asp421 and Asp179, respectively) within a protruding α-helix that grips the V-shaped structure formed by the pincer. Most of the positively selected sites in MDA5 are in regions unique to this RLR, including a characteristic insertion within the helicase domain. Additional selected sites are located at the contact interface between MDA5 monomers, in spatial proximity to a positively selected human polymorphism (Arg843His), and immediately external to the parainfluenza virus 5 V protein (PIV5) binding region. Structural analyses suggested that the positively selected His834 residue is involved in PIV5 binding. Data herein suggest that RLRs have been engaged in host-virus genetic conflict leading to diversifying selection, and indicate parallel evolution at the same site in RIG-I and LGP2, a position likely to be of central importance in antiviral responses.
? 2013.
KEYWORDS:
BEB, BS-REL, Bayes empirical Bayes, C-terminal regulatory domain, CARD, CTD, GARD, HEL, HSV, Herpes simplex virus, IAV, Influenza A virus, LGP2, MDA5, MEME, NLR, NOD-like receptors, PAML, PAMPs, PIV5, PRR, Phylogenetic Analysis by Maximum Likelihood, RIG-I, RIG-I like receptors, RIG-I-like receptors, RLRs, RSV, Retinoic acid-inducible gene 1, SLAC, TLR, TOSV, Toll-like receptors, Toscana virus, branch site-random effects likelihood, caspase activation and recruitment domain, dN/dS, evolution, genetic algorithm recombination detectionFDR, false discovery rate, helicase domain, host-virus genetic conflict, laboratory of genetics and physiology 2, melanoma differentiation associated gene 5, mixed effects model of evolution, non-synonymous substitution/synonymous substitution rate (dN/dS), parainfluenza virus 5 V protein, pathogen-associated molecular patterns, pattern recognition receptors, positive selection, respiratory syncytial virus, single-likelihood ancestor counting
PMID:
24211720
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24211720
RIG-1-like receptors evolved adaptively in mammals, with parallel evolution at LGP2 and RIG-I.
Cagliani R, Forni D, Tresoldi C, Pozzoli U, Filippi G, Rainone V, De Gioia L, Clerici M, Sironi M.
Source
Scientific Institute IRCCS E. Medea, 23842 Bosisio Parini (LC), Italy.
Abstract
RIG-I-like receptors (RLRs) are nucleic acid sensors that activate antiviral innate immune response. These molecules recognize diverse non-self RNA substrates and are antagonized by several viral inhibitors. We performed an evolutionary analysis of RLR genes (RIG-I, MDA5, and LGP2) in mammals. Results indicated that purifying selection had a dominant role in driving the evolution of RLRs. However, application of maximum-likelihood analyses identified several positions that evolved adaptively. Positively selected sites are located in all domains of MDA5 and RIG-I, whereas in LGP2 they are confined to the helicase domain. In both MDA5 and RIG-I, the linkers separating the CARD and helicase domains represented preferential targets of positive selection. Independent selective events in RIG-I and LGP2 targeted the corresponding site (Asp421 and Asp179, respectively) within a protruding α-helix that grips the V-shaped structure formed by the pincer. Most of the positively selected sites in MDA5 are in regions unique to this RLR, including a characteristic insertion within the helicase domain. Additional selected sites are located at the contact interface between MDA5 monomers, in spatial proximity to a positively selected human polymorphism (Arg843His), and immediately external to the parainfluenza virus 5 V protein (PIV5) binding region. Structural analyses suggested that the positively selected His834 residue is involved in PIV5 binding. Data herein suggest that RLRs have been engaged in host-virus genetic conflict leading to diversifying selection, and indicate parallel evolution at the same site in RIG-I and LGP2, a position likely to be of central importance in antiviral responses.
? 2013.
KEYWORDS:
BEB, BS-REL, Bayes empirical Bayes, C-terminal regulatory domain, CARD, CTD, GARD, HEL, HSV, Herpes simplex virus, IAV, Influenza A virus, LGP2, MDA5, MEME, NLR, NOD-like receptors, PAML, PAMPs, PIV5, PRR, Phylogenetic Analysis by Maximum Likelihood, RIG-I, RIG-I like receptors, RIG-I-like receptors, RLRs, RSV, Retinoic acid-inducible gene 1, SLAC, TLR, TOSV, Toll-like receptors, Toscana virus, branch site-random effects likelihood, caspase activation and recruitment domain, dN/dS, evolution, genetic algorithm recombination detectionFDR, false discovery rate, helicase domain, host-virus genetic conflict, laboratory of genetics and physiology 2, melanoma differentiation associated gene 5, mixed effects model of evolution, non-synonymous substitution/synonymous substitution rate (dN/dS), parainfluenza virus 5 V protein, pathogen-associated molecular patterns, pattern recognition receptors, positive selection, respiratory syncytial virus, single-likelihood ancestor counting
PMID:
24211720
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24211720