MHC Architecture in Amphibians—Ancestral Reconstruction, Gene Rearrangements, and Duplication Patterns

The hypervariable major histocompatibility complex (MHC) is a crucial component of vertebrate adaptive immunity, but large-scale studies on MHC macroevolution in nonmodel vertebrates have long been constrained by methodological limitations. Here, we used rapidly accumulating genomic data to reconstruct macroevolution of the MHC region in amphibians. We retrieved contigs containing the MHC region from genome assemblies of 32 amphibian species and examined major structural rearrangements, duplication patterns, and gene structure across the amphibian phylogeny. Based on the few available caecilian and urodele genomes, we showed that the structure of ancestral MHC region in amphibians was probably relatively simple and compact, with a close physical linkage between MHC-I and MHC-II regions. This ancestral MHC architecture was generally conserved in anurans, although the evolution of class I subregion proceeded toward more extensive duplication and rapid expansion of gene copy number, providing evidence for dynamic evolutionary trajectories. Although, in anurans, we recorded tandems of duplicated MHC-I genes outside the core subregion, our phylogenetic analyses of MHC-I sequences provided little support for an expansion of nonclassical MHC-Ib genes across amphibian families. Finally, we found that intronic regions of amphibian classical MHC genes were much longer when compared with other tetrapod lineages (birds and mammals), which could partly be driven by the expansion of genome size. Our study reveals novel evolutionary patterns of the MHC region in amphibians and provides a comprehensive framework for further studies on the MHC macroevolution across vertebrates.