International Journal of Molecular Zoology, 2024, Vol.14, No.6, 297-304 http://animalscipublisher.com/index.php/ijmz 298 2 Genetic Basis of the Canine Immune System 2.1 Overview of the canine immune system The canine immune system, like that of other vertebrates, is composed of innate and adaptive components that work together to protect the host from pathogens (Chen, 2024). The innate immune system provides the first line of defense through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), which detect pathogen-associated molecular patterns (PAMPs) and initiate immediate immune responses (Vaure and Liu, 2014; Vijay, 2018). The adaptive immune system, on the other hand, involves the major histocompatibility complex (MHC) molecules that present antigens to T cells, facilitating a more specific and long-lasting immune response (Migalska et al., 2019). 2.2 Major histocompatibility complex (MHC) in canines The MHC genes are crucial for the adaptive immune response in canines, encoding proteins that present foreign antigens to T cells. These genes exhibit high polymorphism, which is believed to be maintained by pathogen-mediated selection (Bartocillo et al., 2021). In canines, MHC class I molecules, such as DLA-88*50801, have been structurally characterized to reveal diverse peptide-binding modes, which are essential for recognizing a wide array of pathogens (Xiao et al., 2016). Studies on raccoon dogs, a non-model canid species, have shown that MHC class I genes are subject to positive selection and balancing selection, indicating their evolutionary adaptation to pathogen pressures. 2.3 Toll-like receptors (TLRs) and pathogen recognition TLRs are a family of PRRs that play a pivotal role in the innate immune system by recognizing PAMPs and initiating immune responses (Figure 1) (Fitzgerald and Kagan, 2020). In canines, TLRs such as TLR2, TLR4, and TLR5 are involved in recognizing bacterial components and other pathogens (Quéméré et al., 2015). These receptors are highly polymorphic, which allows for a broad recognition spectrum and adaptability to various pathogens (Minias et al., 2021). The expression and functionality of TLR4, for instance, vary across different species, including dogs, which has implications for vaccine development and therapeutic interventions. The evolutionary dynamics of TLRs in canines suggest that these receptors are under continuous selection pressure to maintain their diversity and functionality in pathogen recognition (Quéméré et al., 2021). 3 Impact of Domestication on Immune Genes 3.1 Evolutionary changes in immune genes during domestication Domestication has significantly influenced the evolution of immune genes in canids. Structural variations (SVs) in the genome, such as insertions, deletions, and translocations, have been identified as key factors in the domestication process. These SVs are particularly enriched in genes associated with immune systems, indicating that immune function has been a critical area of adaptation during domestication (Wang et al., 2018). For instance, the insertion of a new copy of the AKR1B1 gene in dogs, which is highly expressed in the small intestine and liver, suggests an enhanced ability for de novo fatty acid synthesis and antioxidant activity, likely in response to dietary changes during the agricultural revolution. 3.2 Adaptation to human-influenced environments The adaptation of canids to human-influenced environments has also shaped their immune systems. The shift from wild habitats to human-dominated landscapes exposed domestic dogs to a new range of pathogens, necessitating changes in their immune responses. This is evident in the increased expression of immune-related genes and the presence of structural variations that enhance immune function. Additionally, the European roe deer, which has expanded into agricultural landscapes, shows that exposure to new pathogens can drive the evolution of immune genes, such as toll-like receptors (TLRs), which continue to evolve dynamically in response to pathogen-mediated positive selection (Quéméré et al., 2015). 3.3 Genetic bottlenecks and immune gene diversity Domestication has also led to genetic bottlenecks, which have had a profound impact on immune gene diversity. Small population sizes during domestication and strong artificial selection for specific traits have increased the
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