Evolution by selection, recombination, and gene duplication in MHC class I genes of two Rhacophoridae species

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.

Extensive diversification of MHC in Chinese giant salamanders Andrias davidianus (Anda-MHC) reveals novel splice variants

“…The variability are concentrated in the a1/a2, a1, and b1 domains that correspond to the putative PBR, which allows MHC molecules to present a large array of antigen peptides to T cells. As the first terrestrial tetrapods, amphibians are exposed to a broader range of pathogens compared with ancestral aquatic fishes (Zhao et al, 2013). Therefore, the high level of MHC diversity could increase the ability of individual to combat pathogen infection.…”

Limited polymorphism of the functional MHC class II B gene in the black‐spotted frog (Pelophylax nigromaculatus) identified by locus‐specific genotyping

“…Genetic diversity was investigated using a 279‐bp MHCIA fragment comprising 15 codons coding antigen‐binding sites, which is much less than in the MHCIIB gene. (Gong et al., ; Zhao et al., ).…”

The evolution of the major histocompatibility complex in upstream versus downstream river populations of the longnose dace

“…We were able to test for negative frequency‐dependent selection by inferring an excess of nonsynonymous substitutions, suggesting that nonsynonymous mutations are subject to positive selection, whereas synonymous mutations are often lost due to drift. Most estimates of dN and dS do not accommodate intragenic recombination, which has been shown to shape MHC diversity in a number of systems (e.g., Gómez, Conejeros, Marshall, & Consuegra, ; Lam, Shen, Chia, Chan, & Ren, ; Zhao et al., ). Recombination within a gene can distort any detectable patterns of selection on the gene (Ramírez‐Soriano, Ramos‐Onsins, Rozas, Calafell, & Navarro, ; Wilson & McVean, ) because analyses are based on correlations between polymorphic sites and nucleotide differences, or synonymous and nonsynonymous sites and mutations, along an entire sequence.…”

“…We were able to test for negative frequency-dependent selection by inferring an excess of nonsynonymous substitutions, suggesting that nonsynonymous mutations are subject to positive selection, whereas synonymous mutations are often lost due to drift. Most estimates of dN and dS do not accommodate intragenic recombination, which has been shown to shape MHC diversity in a number of systems (e.g., Gómez, Conejeros, Marshall, & Consuegra, 2010;Lam, Shen, Chia, Chan, & Ren, 2013;Zhao et al, 2013).…”