A global analysis of selection at the avian MHC

Recent advancements in sequencing technology have resulted in rapid progress in the study of the major histocompatibility complex (MHC) in non‐model avian species. Here, we analyze a global dataset of avian MHC class I and class II sequences (ca. 11,000 sequences from over 250 species) to gain insight into the processes that govern macroevolution of MHC genes in birds. Analysis of substitution rates revealed striking differences in the patterns of diversifying selection between passerine and non‐passerine birds. Non‐passerines showed stronger selection at MHC class II, which is primarily involved in recognition of extracellular pathogens, while passerines showed stronger selection at MHC class I, which is involved in recognition of intracellular pathogens. Positions of positively selected amino‐acid residues showed marked discrepancies with peptide‐binding residues (PBRs) of human MHC molecules, suggesting that using a human classification of PBRs to assess selection patterns at the avian MHC may be unjustified. Finally, our analysis provided evidence that indel mutations can make a substantial contribution to adaptive variation at the avian MHC.