International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 22-31 http://animalscipublisher.com/index.php/ijmvr 26 al., 2023). In situations of high host diversity and high rates of interspecies contact, risk of spillover is higher. For instance, CPV-2 and CDV have been identified with evidence of ongoing transmission from pet dogs to free-ranging canids, either recent host jump genetic signatures or ancient ones (Chen et al., 2024). Early warning and risk management require ecological interface monitoring and adaptive mutation tracking. 5 Comparative Analysis of Host Genomes and Immune Systems 5.1 Genomic differences between domestic dogs and wild species and their impact on immune response Whole-genome comparisons indicate that while domestic dogs and free-ranging canids (e.g., wolves) share similar percentages of copy number variation (CNV), domestic dogs and free-ranging canids are very different in loci rich in immune response, sensory perception, and metabolic process (Wang et al., 2018). Structural variants like segmental duplications and insertions are associated with disease-susceptible and immune function genes, and involve both natural and artificial selection in domestication. Species-specific methylation patterns and epigenetic variation also explain immune system variation and, possibly, contribute to disease resistance and phenotypic diversification (Figure 2). Figure 2 Structural variation in the dog genome. (a) Circle diagram showing SVs detected by the dog-dhole alignment (yellow) and the dog-wolf alignment (black). (b) SVs in the dog genome by identified by multiz alignment. Each ring from the inner ring outwards represents translocations, insertions, deletions, repeats and inversions, respectively (Adopted from Wang et al., 2018) 5.2 Diversity and evolution of key immune-related genes Major histocompatibility complex (MHC) and toll-like receptors (TLRs) are highly polymorphic and subject to intense pathogen-directed selection in domestic and wild canids (Vinkler et al., 2023). Wolves possess a high MHC I and TLR diversity with evidence of balancing and positive selection within antigen-binding sites and pathogen recognition sites. Fresh MHC alleles are beneficial by promoting resistance to infection, justifying the function of immunogenetic innovation in coevolution between host and pathogen. MHC diversity is higher in pathogen-exposed wild populations with diverse pathogens and human-induced stresses. 5.3 Co-evolutionary relationships between host and pathogen gene networks Coevolution of host and pathogen diversifies immune gene networks, typically resulting in Red Queen evolution in which hosts and pathogens evolve repeatedly (Vinkler et al., 2023). Disease resistance is typically polygenic, involving both core and peripheral immune genes, and is affected by concurrent exposure to many pathogens exerting various selection pressures (Vinkler et al., 2023). Pathogen-driven selection maintains polymorphism in both adaptive genes, i.e., MHC, and innate immunity genes, i.e., TLRs, with different pathogens exerting antagonistic or synergistic selection.
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