Palaeognaths Reveal Evolutionary Ancestry of the Avian Major Histocompatibility Complex Class II.

The multigene family of the major histocompatibility complex (MHC) codes for the key antigen-presenting molecules of the vertebrate immune system. In birds, duplicated MHC class II (MHC-II) genes are highly homogenized by concerted evolution, and thus, identification of their orthologous relationships across long evolutionary timescales remains challenging. Relatively low evolutionary rate of avian MHC class IIA genes has been expected to provide a promising avenue to allow such inferences, but availability of MHC-IIA sequences in nonmodel bird species has been limited until recently. Here, taking advantage from accumulating genomic resources, we identified and analyzed MHC-IIA sequences from the most basal lineage of extant birds (Palaeognathae). Conserved region of the MHC-IIA membrane-proximal domain was used to search for orthologous relationships between palaeognath birds and nonavian reptiles. First, analyses of palaeognath sequences revealed the presence of a separate MHC-IIA gene lineage (DAA3) in kiwis, which did not cluster with previously described avian MHC-IIA lineages (DAA1 and DAA2). Next, phylogenetic reconstruction showed that kiwi DAA3 sequences form a single well-supported cluster with turtle MHC-IIA. High similarity of these sequences most likely reflects their remarkable evolutionary conservation and retention of ancient orthologous relationships, which can be traced back to basal archosauromorphs ca. 250 million years ago. Our analyses offer novel insights into macroevolutionary history of the MHC and reinforce the view that rapid accumulation of high-quality genome assemblies across divergent nonmodel species can substantially advance our understanding of gene evolution.