Computational analyses of an evolutionary arms race between mammalian immunity mediated by immunoglobulin A and its subversion by bacterial pathogens

Ana Pinheiro, Jenny M. Woof, Laurent Abi-Rached, Peter Parham, Pedro J. Esteves

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)

    Abstract

    IgA is the predominant immunoglobulin isotype in mucosal tissues and external secretions, playing important roles both in defense against pathogens and in maintenance of commensal microbiota. Considering the complexity of its interactions with the surrounding environment, IgA is a likely target for diversifying or positive selection. To investigate this possibility, the action of natural selection on IgA was examined in depth with six different methods: CODEML from the PAML package and the SLAC, FEL, REL, MEME and FUBAR methods implemented in the Datamonkey webserver. In considering just primate IgA, these analyses show that diversifying selection targeted five positions of the Ca1 and Ca2 domains of IgA. Extending the analysis to include other mammals identified 18 positively selected sites: ten in Ca1, five in Ca2 and three in Ca3. All but one of these positions display variation in polarity and charge. Their structural locations suggest they indirectly influence the conformation of sites on IgA that are critical for interaction with host IgA receptors and also with proteins produced by mucosal pathogens that prevent their elimination by IgA-mediated effector mechanisms. Demonstrating the plasticity of IgA in the evolution of different groups of mammals, only two of the eighteen selected positions in all mammals are included in the five selected positions in primates. That IgA residues subject to positive selection impact sites targeted both by host receptors and subversive pathogen ligands highlights the evolutionary arms race playing out between mammals and pathogens, and further emphasizes the importance of IgA in protection against mucosal pathogens.

    Original languageEnglish
    Article numbere73934
    Number of pages9
    JournalPLoS ONE
    Volume8
    Issue number9
    DOIs
    Publication statusPublished - 3 Sep 2013

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