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

PLoS One. 2013 Sep 3;8(9):e73934. doi: 10.1371/journal.pone.0073934. eCollection 2013.

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 Cα1 and Cα2 domains of IgA. Extending the analysis to include other mammals identified 18 positively selected sites: ten in Cα1, five in Cα2 and three in Cα3. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacteria / pathogenicity*
  • Biological Evolution*
  • Codon
  • Computational Biology*
  • Immunoglobulin A / chemistry
  • Immunoglobulin A / physiology*
  • Mammals / immunology*
  • Models, Molecular
  • Molecular Sequence Data
  • Selection, Genetic

Substances

  • Codon
  • Immunoglobulin A

Grants and funding

The Portuguese Foundation for Science and Technology (www.fct.pt) supported the doctoral fellowship of Ana Pinheiro (SFRH/BD/71252/2010) and the post-doctoral fellowship of Pedro J. Esteves (SPRH/BPD/27021/2006). This work was also supported by a project of the Portuguese Foundation for Science and Technology (PTDC/BIA-BEC/103158/2008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.