Comparative analysis of bat immunoglobulin constant regions identifies adaptations of bat immunity

Our understanding of bat immunoglobulins (Igs) and their functions remains limited despite the importance of Ig activation in both innate and adaptive immune responses. Positive selection is known to act on other immune genes needed to mount adaptive immune responses, suggesting that selection may also act on bat Ig constant regions. To test whether bat Ig constant regions have evolved adaptations related to immunity, we reconstructed the evolutionary relationships of the constant region of bat IgM, IgA, and IgG genes and analyzed their sequences for signs of selection. Our phylogenies yielded topologies that generally agreed with known evolutionary relationships between bat families and indicated that some branches preceding large species radiation underwent positive selection. At the amino acid level, we found positive selection near sites where IgM and IgG constant regions interact with the C1q complex. Positive signals also clustered around sites where IgM and IgA interact with Fc alpha/mu receptor (Fcα/µR) and where IgG interacts with neonatal Fc receptor (FcrRn) and tripartite motif containing 21 (TRIM21). Because Ig binding to C1q, Fcα/µR, FcrRn, and TRIM21 promotes innate and adaptive immune responses in mice and humans, our findings suggest a similar role for Igs in bat immune responses.