The mouse B cell-specific mb-1 gene encodes an immunoreceptor tyrosine-based activation motif (ITAM) protein that may be evolutionarily conserved in diverse species by purifying selection

Richard Sims, Virginia Oberholzer Vandergon, Cindy S. Malone

The B-lymphocyte accessory molecule Ig-alpha (Ig-α) is encoded by the mouse B cell-specific gene (mb-1), and along with the Ig-beta (Ig-β) molecule and a membrane bound immunoglobulin (mIg) makes up the B-cell receptor (BCR). Ig-α and Ig-β form a heterodimer structure that upon antigen binding and receptor clustering primarily initiates and controls BCR intracellular signaling via a phosphorylation cascade, ultimately triggering an effector response. The signaling capacity of Ig-α is contained within its immunoreceptor tyrosine-based activation motif (ITAM), which is also a key component for intracellular signaling initiation in other immune cell-specific receptors. Although numerous studies have been devoted to the mb-1 gene product, Ig-α, and its signaling mechanism, an evolutionary analysis of the mb-1 gene has been lacking until now. In this study, mb-1 coding sequences from 19 species were compared using Bayesian inference. Analysis revealed a gene phylogeny consistent with an expected species divergence pattern, clustering species from the primate order separate from lower mammals and other species. In addition, an overall comparison of non-synonymous and synonymous nucleotide mutational changes suggests that the mb-1 gene has undergone purifying selection throughout its evolution.