Abstract
BackgroundThe 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.ResultsThree 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.ConclusionsThe 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.
Highlights
The mammalian Major Histocompatibility Complex (MHC) is a genetic region containing highly polymorphic genes with immunological functions
The potentially functional genes were numbered based on their position on the equine physical map, DRB1DRB3 and DQB1-DQB3, which corresponds to numbering by Viluma et al [24]
A comparison of its flanking regions found in the Burgud genome and the reference genome EquCab3.0 showed that the downstream flanking sequence from Burgud was highly similar (99% sequence identity) to a DQB2 downstream flanking sequence from EquCab3.0
Summary
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 mammalian Major Histocompatibility Complex (MHC) is a large genetic region of approximately 4 Mb containing about 230 protein coding genes, many of them encoding molecules with immunological functions. The MHC class II region is a complex region containing different sub-regions with variable numbers of often highly polymorphic genes. Class II molecules coding for antigen presenting molecules are heterodimeric glycoproteins consisting of an α and a β chain encoded by MHC class II genes DRA/DQA and DRB/DQB, respectively. The exon 2 sequences of the MHC loci encoding antigenpresenting molecules likely evolved under strong selection pressure of pathogens [5]
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