Balancing selection and recombination drive genetic variation at MHC class I genes in the giant panda

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  • ReceivedOct 13, 2014
  • AcceptedOct 27, 2014
  • PublishedJan 7, 2015


Major histocompatibility complex (MHC) is a family of highly polymorphic genes activating adaptive immunity in vertebrates. However, the underlying mechanism of MHC evolution is still not fully understood. In this study, we investigated genetic variation of three classical MHC class I genes in the giant panda (Ailuropoda melanoleuca) and tested for selection effect and recombination event across exonic and intronic sequences to understand maintenance mechanism of polymorphism at Aime-MHC class I genes. In total, we isolated 21 MHC class I haplotypes (exon 2-intron 2-exon 3) from 46 captive giant pandas, of which eight were for Aime-C, seven for Aime-I and six for Aime-L; however, we only identified six unique sequences from these haplotypes. The subsequent maximum-likelihood and Chi-square analyses both detected evidence of recombination acting on the 21 haplotypes. These results indicate that the giant panda still retains a relatively high adaptive variation at Aime-MHC-I genes, and that the intronic segments have been homogenized along evolutionary time by recombination and subsequent genetic drift. We calculated nucleotide substitution rates of the antigen-binding regions (exons 2 and 3) and the noncoding intron 2, and found two pieces of evidence supporting the presence of balancing selection in the giant panda: an excess of nonsynonymous over synonymous substitutions at the antigen-binding sites, and an obviously higher synonymous substitutions in the exons than nucleotide substitutions in the intron. Thus, this study reveals that balancing selection and recombination together shape the diversity pattern at Aime-MHC-I loci of the giant panda.


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