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MBE Advance Access published online on April 15, 2009

Molecular Biology and Evolution, doi:10.1093/molbev/msp074
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© The Author 2009. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

The evolutionarily dynamic IFN-inducible GTPase proteins play conserved immune functions in vertebrates and cephalochordates

Guang Li, Juyong Zhang, Yi Sun, Hua Wang and Yiquan Wang

Key Laboratory of Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, 361005, China

Corresponding author: Yiquan Wang; Address: School of Life Sciences, Xiamen University, Xiamen, Fujian, 361005, China. Tel: +86-592-2184427; Fax: +86-592-2181015. E-mail: wangyq{at}xmu.edu.cn

Received for publication January 22, 2009. Revision received March 8, 2009. Revision received April 5, 2009. Accepted for publication April 8, 2009.

IFN-inducible GTPases currently include four families of proteins: myxovirus resistant proteins (Mxs), guanylate binding proteins (GBPs), immunity-related GTPase proteins (IRGs) and very large inducible GTPase proteins (VLIGs). They are all under conserved regulation by IFNs in humans and mice, and play a critical role in preventing microbial infections. However, differences between vertebrates are poorly characterized and their evolutionary origins have not been studied in detail. In this study, we performed comparative genomic analysis of the four families in eighteen representative animals which yielded several unexpected results. Firstly, we found that Mx, GBP and IRG protein families arose before the divergence of chordate subphyla, but VLIG emerged solely in vertebrates. Secondly, IRG, GBP and VLIG families have experienced a high rate of gene gain and loss during the evolution, with the GBP family being lost entirely in two pufferfish and VLIG family lost in primates and carnivores. Thirdly, the regulation of these genes by IFNs is highly conserved throughout vertebrates although the VLIG protein sequences in fish have lost the first 870 amino acid residues. Finally, amphioxus IFN-inducible GTPase genes are all highly expressed in immune-related organs such as gill, liver and intestine, and are up-regulated after challenge with PolyI:C and pathogens, although no IFNs or their receptors (IFNRs) were detected in the current amphioxus genome database. These results suggest that IFN-inducible GTPase genes play conserved immune functions both in vertebrates and in cephalochordates.

Key Words: IFN-inducible GTPase protein coding genes • immune function • vertebrates • amphioxus • evolution


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