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Gamma Chain Receptor Interleukins: Evidence for Positive Selection Driving the Evolution of Cell-to-Cell Communicators in the Mammalian Immune System

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Abstract

The interleukin-2 receptor (IL-2R) γ chain, or common γ chain (γc), is the hub of a protein interaction network in the mammalia that is central to defense against disease. It is the indispensable subunit of the functional receptor complexes for a group of interleukins known as the γ-chain-dependent interleukins (IL-2, IL-4, -7, -9, -15, and -21). The γc links these proteins through their interaction with it and their competition for its recruitment. The γc-dependent interleukins also interact with each other to either enhance or suppress expression through manipulation of expression of receptor subunits. Given the influence of protein–protein interactions on evolution, such as those documented for many genes including the reproductive proteins of the sperm and egg coat, here we have asked whether there is a common thread in the evolution of these interleukins. Our findings indicate that positive selection has acted by fixing a large number of amino acid replacement mutations in every single one of these interleukins, this adaptive evolution is also observed in a lineage-specific manner. Crucially, however, there does not appear to have ever been an instance of adaptive evolution in the γc chain itself, thereby providing an insight into the evolution of this hub protein. These findings highlight the importance of adaptive evolutionary events in the evolution of this central network in the immune system and suggest underlying causes for differences in defense responses in the mammalia.

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Acknowledgments

We would like to thank the HEA for funding this work under the PRTLI scheme. We would also like to thank Dr. Christopher J. Creevey and Dr. Simon A. Travers for their contribution to the phylogeny reconstruction.

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Authors and Affiliations

  1. Bioinformatics and Molecular Evolution Laboratory, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

    Mary J. O’Connell

  2. Bioinformatics and Pharmacogenomics Laboratory, Department of Biology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland

    James O. McInerney

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  1. Mary J. O’Connell
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  2. James O. McInerney
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Correspondence to James O. McInerney.

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[Reviewing Editor: Dr. Willie J. Swanson]

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O’Connell, M.J., McInerney, J.O. Gamma Chain Receptor Interleukins: Evidence for Positive Selection Driving the Evolution of Cell-to-Cell Communicators in the Mammalian Immune System. J Mol Evol 61, 608–619 (2005). https://doi.org/10.1007/s00239-004-0313-3

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