Canine major histocompatibility complex class I (MHC-I) diversity landscape

Abstract

The genes of the Major Histocompatibility Complex class I (MHC-I) are among the most diverse in the mammalian genome, playing a crucial role in immunology. Understanding the diversity landscape of MHC-I is therefore of paramount importance. The dog is a key translational model in various biomedical fields. However, our understanding of the canine MHC-I diversity landscape lags significantly behind that of humans. To address this deficiency, we used our newly developed software, KPR de novo assembler and genotyper, to genotype 1,325 samples from 1,025 dogs with paired-end RNA-seq data from 43 BioProjects, after extensive quality control. Among 926 dogs that pass the QC, 591 dogs (64%) have at least one allele genotyped, and a total of 97 known alleles and 52 putative new alleles were identified. Further analysis reveals that DLA-I gene expression levels vary among the tissues, with lowest for testis and brain tissues and highest for blood, corpus luteum, and spleen. We identified dominant alleles in each of the 17 canine breeds, as well as among the entire canine population. Furthermore, our analysis also identifies breed-specific alleles and mutually co-occurred/exclusive alleles. Our study indicates that canine DLA-88 is as diversified as human HLA-A/B/C genes within the entire population, but less diversified within a breed than with HLA-A/B/C within an ethnic group. Lastly, we examined the hypervariable regions (HVR) within or across human/canine MHC-I alleles and found that 80% of the HVRs overlap between the two species. We further noted that 80% of the HVRs are within 4A contact with the peptides, and that the dog-human difference overlaps with only 20% HVRs. Our research offers valuable insights for immunological studies involving dogs.