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 caspase activation and recruitment domain and the helicase domain 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 binding region. Structural analyses suggested that the positively selected His834 residue is involved in parainfluenza virus 5 V protein 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 Elsevier Ltd.
Cagliani, R., Forni, D., Tresoldi, C., Pozzoli, U., Filippi, G., Rainone, V., et al. (2014). RIG-I-like receptors evolved adaptively in mammals, with parallel evolution at LGP2 and RIG-I. JOURNAL OF MOLECULAR BIOLOGY, 426(6), 1351-1365 [10.1016/j.jmb.2013.10.040].
|Citazione:||Cagliani, R., Forni, D., Tresoldi, C., Pozzoli, U., Filippi, G., Rainone, V., et al. (2014). RIG-I-like receptors evolved adaptively in mammals, with parallel evolution at LGP2 and RIG-I. JOURNAL OF MOLECULAR BIOLOGY, 426(6), 1351-1365 [10.1016/j.jmb.2013.10.040].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||RIG-I-like receptors evolved adaptively in mammals, with parallel evolution at LGP2 and RIG-I|
|Autori:||Cagliani, R; Forni, D; Tresoldi, C; Pozzoli, U; Filippi, G; Rainone, V; De Gioia, L; Clerici, M; Sironi, M|
|Data di pubblicazione:||2014|
|Rivista:||JOURNAL OF MOLECULAR BIOLOGY|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.jmb.2013.10.040|
|Appare nelle tipologie:||01 - Articolo su rivista|