Abstract
BackgroundComparison of major histocompatibility complex (MHC) genes across vertebrate species can reveal molecular mechanisms underlying the evolution of adaptive immunity-related proteins. As the first terrestrial tetrapods, amphibians deserve special attention because of their exposure to probably increased spectrum of microorganisms compared with ancestral aquatic fishes. Knowledge regarding the evolutionary patterns and mechanisms associated with amphibian MHC genes remains limited. The goal of the present study was to isolate MHC class I genes from two Rhacophoridae species (Rhacophorus omeimontis and Polypedates megacephalus) and examine their evolution.ResultsWe identified 27 MHC class I alleles spanning the region from exon 2 to 4 in 38 tree frogs. The available evidence suggests that these 27 sequences all belong to classical MHC class I (MHC Ia) genes. Although several anuran species only display one MHC class Ia locus, at least two or three loci were observed in P. megacephalus and R. omeimontis, indicating that the number of MHC class Ia loci varies among anuran species. Recombination events, which mainly involve the entire exons, played an important role in shaping the genetic diversity of the 27 MHC class Ia alleles. In addition, signals of positive selection were found in Rhacophoridae MHC class Ia genes. Amino acid sites strongly suggested by program to be under positive selection basically accorded with the putative antigen binding sites deduced from crystal structure of human HLA. Phylogenetic relationships among MHC class I alleles revealed the presence of trans-species polymorphisms.ConclusionsIn the two Rhacophoridae species (1) there are two or three MHC class Ia loci; (2) recombination mainly occurs between the entire exons of MHC class Ia genes; (3) balancing selection, gene duplication and recombination all contribute to the diversity of MHC class Ia genes. These findings broaden our knowledge on the evolution of amphibian MHC systems.
Highlights
Comparison of major histocompatibility complex (MHC) genes across vertebrate species can reveal molecular mechanisms underlying the evolution of adaptive immunity-related proteins
We constructed a phylogenetic tree using the 27 alleles and all of the published MHC class I genes from anurans with comparable coverage to resolve their phylogenetic status
We found that MHC class Ia genes and MHC class Ib genes clustered separately, and all of the 27 Rhacophoridae alleles belonged to the MHC class Ia gene cluster (Figure 1)
Summary
Comparison of major histocompatibility complex (MHC) genes across vertebrate species can reveal molecular mechanisms underlying the evolution of adaptive immunity-related proteins. Genes of the major histocompatibility complex (MHC) encode cell surface glycoproteins that present self and foreign (e.g., pathogens) peptides to T lymphocytes to trigger the appropriate adaptive immune response. These glycoproteins can be divided into two major subgroups: class I and class II MHC molecules, which recognize intracellular and extracellular antigens, respectively. The heavy chain has a cytoplasmic region, a trans-membrane region, and three extracellular domains designated α1, α2, and α3 that are encoded by exons 2–4 of the MHC class I genes. Non-classical MHC class I (MHC class Ib) genes possess fewer polymorphisms, are expressed at lower levels in fewer tissues, and perform different functions despite having similar sequences [5,6]
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