TY - JOUR
T1 - Functional evolution of the OAS1 viral sensor
T2 - Insights from old world primates
AU - Fish, Ian
AU - Boissinot, Stéphane
N1 - Funding Information:
The work was conducted in part with equipment from the Core Facilities for Imaging, Cellular and Molecular Biology at Queens College. This research was supported by the Professional Staff Congress- City University of New York grant 66642–00 44 to S.B. This investigation used resources that were supported by the Southwest National Primate Research Center grant P51 RR013986 from the National Center for Research Resources, National Institutes of Health, and that are currently supported by the Office of Research Infrastructure Programs through P51 OD011133. We thank two anonymous reviewers for their comments on an earlier version of the manuscript.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Infections with viral pathogens impose considerable selective pressure on host defensive genes. Those genes at the forefront, responsible for identifying and binding exogenous molecular viral components, will carry the hallmarks of this struggle. Oligoadenylate synthetase (OAS) enzymes play a major role in the innate defense against a large number of viruses by acting as sensors of viral infections. Following their up-regulation by the interferon pathway, OASs bind viral dsRNA and then signal ribonuclease L (RNase L) to degrade RNA, shutting down viral and host protein synthesis. We have investigated the evolution of OAS1 in twenty-two Old World monkey species. We identified a total of 35 codons with the earmarks of positive selection and we performed a comprehensive analysis of their functional significance using in silico modeling of the OAS1 protein. Subdividing OAS1 into functional domains revealed intense purifying selection in the active domain but significant positive directional selection in the RNA-binding domain (RBD), the region where OAS1 binds viral dsRNA. The modeling analysis revealed a concentration of rapidly evolving residues in one region of the RBD suggestive of the sub-functionalization of different regions of the RBD. This analysis also identified several positively selected residues circumscribing the entry to the active site suggesting adaptive evasion of viral antagonism and/or selection for production of oligoadenylate of different length.
AB - Infections with viral pathogens impose considerable selective pressure on host defensive genes. Those genes at the forefront, responsible for identifying and binding exogenous molecular viral components, will carry the hallmarks of this struggle. Oligoadenylate synthetase (OAS) enzymes play a major role in the innate defense against a large number of viruses by acting as sensors of viral infections. Following their up-regulation by the interferon pathway, OASs bind viral dsRNA and then signal ribonuclease L (RNase L) to degrade RNA, shutting down viral and host protein synthesis. We have investigated the evolution of OAS1 in twenty-two Old World monkey species. We identified a total of 35 codons with the earmarks of positive selection and we performed a comprehensive analysis of their functional significance using in silico modeling of the OAS1 protein. Subdividing OAS1 into functional domains revealed intense purifying selection in the active domain but significant positive directional selection in the RNA-binding domain (RBD), the region where OAS1 binds viral dsRNA. The modeling analysis revealed a concentration of rapidly evolving residues in one region of the RBD suggestive of the sub-functionalization of different regions of the RBD. This analysis also identified several positively selected residues circumscribing the entry to the active site suggesting adaptive evasion of viral antagonism and/or selection for production of oligoadenylate of different length.
KW - Cercopithecidae
KW - Immune system evolution
KW - Innate immunity
KW - OAS1
KW - Positive selection
KW - dsRNA sensor
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U2 - 10.1016/j.meegid.2016.07.005
DO - 10.1016/j.meegid.2016.07.005
M3 - Article
C2 - 27393659
AN - SCOPUS:84980361811
VL - 44
SP - 341
EP - 350
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
SN - 1567-1348
ER -