Genetic diversity, evolution and selection in the major histocompatibility complex DRB and DQB loci in the family Equida
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RESEARCH ARTICLE
Open Access
Genetic diversity, evolution and selection in the major histocompatibility complex DRB and DQB loci in the family Equidae Marie Klumplerova1,2, Petra Splichalova1,2, Jan Oppelt2,3,4, Jan Futas1,2, Aneta Kohutova1,5, Petra Musilova6,7, Svatava Kubickova6,7, Roman Vodicka8, Ludovic Orlando9,10 and Petr Horin1,2*
Abstract Background: The mammalian Major Histocompatibility Complex (MHC) is a genetic region containing highly polymorphic genes with immunological functions. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. The MHC class II sub-region contains genes expressed in antigen presenting cells. The antigen binding site is encoded by the second exon of genes encoding antigen presenting molecules. The exon 2 sequences of these MHC genes have evolved under the selective pressure of pathogens. Interspecific differences can be observed in the class II sub-region. The family Equidae includes a variety of domesticated, and free-ranging species inhabiting a range of habitats exposed to different pathogens and represents a model for studying this important part of the immunogenome. While equine MHC class II DRA and DQA loci have received attention, the genetic diversity and effects of selection on DRB and DQB loci have been largely overlooked. This study aimed to provide the first in-depth analysis of the MHC class II DRB and DQB loci in the Equidae family. Results: Three DRB and two DQB genes were identified in the genomes of all equids. The genes DRB2, DRB3 and DQB3 showed high sequence conservation, while polymorphisms were more frequent at DRB1 and DQB1 across all species analyzed. DQB2 was not found in the genome of the Asiatic asses Equus hemionus kulan and E. h. onager. The bioinformatic analysis of non-zero-coverage-bases of DRB and DQB genes in 14 equine individual genomes revealed differences among individual genes. Evidence for recombination was found for DRB1, DRB2, DQB1 and DQB2 genes. Trans-species allele sharing was identified in all genes except DRB1. Site-specific selection analysis predicted genes evolving under positive selection both at DRB and DQB loci. No selected amino acid sites were identified in DQB3. Conclusions: The organization of the MHC class II sub-region of equids is similar across all species of the family. Genomic sequences, along with phylogenetic trees suggesting effects of selection as well as trans-species polymorphism support the contention that pathogen-driven positive selection has shaped the MHC class II DRB/ DQB sub-regions in the Equidae. Keywords: Major histocompatibility complex, Family Equidae, MHC exon 2, MHC class II loci, Positive selection, Trans-species polymorphism, Selected amino acid sites * Correspondence: [email protected] 1 Department of Animal Genetics, Veterinary and Pharmaceutical University, Brno, Czech Republic 2 Ceitec VFU, RG Animal Immunogenomics, Brno, Czech Republic Full list of author information is available at the end of the article © The Author(s). 2020 Open Access T
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