International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 22-31 http://animalscipublisher.com/index.php/ijmvr 23 free-ranging canid-domestic dog contact provides an opportunity for the exchange of pathogens and population genetics, which can potentially make the development of new variants with new virulence or new host range more rapid. Their global distribution and close connection with humans make them important sentinels for the monitoring of zoonotic disease patterns and the extrapolation of the potential risk of spillover events of pathogens (Guzmán et al., 2024; Ricardo et al., 2024). Comparative genomics is an important tool to reveal the genetic diversity, evolutionary past, and adaptative processes of pathogens across their range of hosts. By a genomic comparison of domestic dog and ancestor pathogens, scientists are able to identify core and accessory genes, virulence factors, and host-specificity, immune evasion, and cross-transmission genetic determinants. Genomic sequences also facilitate the construction of phylogenies and pathogen networks through which one can reconstruct the source and evolutionary past of the zoonotic agents. Comparative genomics also facilitates easy design of molecular diagnostics, vaccines, and therapeutic targets based on the recognition of conserved genetic signatures and evolutionary constraints. The combination of genomic information with ecological and epidemiological information increases our ability for prediction and control of zoonotic disease transmission (Paz et al., 2024). The study provides a summary of comparative genomics of zoonotic pathogens in domestic dogs and wildlife canids. It presents main classes of pathogens and their evolutionary characteristics, recapitulates genomic progress in studies that shed light on host adaptation mechanisms and cross-species transmission, and briefly discusses the extension of multi-omics to research on canine pathogens. In addition, it addresses genomic variation in host immune and receptor genes influencing infection susceptibility and pathogen coevolution. Through the synthesis of molecular biology advances, evolutionary genomics, and disease ecology, this study demonstrates the relevance of a comparative genomic strategy to the elucidation of pathogen evolution, zoonotic disease surveillance system optimization, and the guidance of effective prevention and control measure implementation under the One Health umbrella. 2 Overview of Major Zoonotic Pathogens in Domestic Dogs and Wild Relatives 2.1 Viral pathogens Viral zoonoses are some of the most general and lethal zoonoses of canids. Rabies virus (RABV) is one, a globally-disseminated Lyssavirus that annually kills close to 60,000 human beings, domestic dogs being the main reservoir. Wild canids such as wolves and foxes maintain also sylvatic cycles of transmission. Comparative genomics reveals the adaptive mutations in the viral glycoprotein (G) gene that enable host receptor attachment and immune evasion. Similarly, canine distemper virus (CDV), which is a Morbillivirus closely related to measles virus, infects domestic and wild carnivores through cross-species transmission events induced by hemagglutinin (H) gene mutations. Canine coronaviruses (CCoV and CRCoV), on the other hand, have high recombination rates and genetic plasticity, which poses threats of emergence of new coronaviruses with zoonotic potential (Cilia et al., 2021). 2.2 Bacterial pathogens Several bacterial pathogens of major zoonotic importance are transmitted by canids. Leptospira interrogans, which causes leptospirosis, lives in infected canids and wildlife reservoir canids in renal tubules that allow for environmental shedding and indirect human-to-human transmission. Gene characterization identified osmotic stress response and adhesion genes allowing host persistence. Brucella canis, the etiologic agent of canine brucellosis, possesses typical genomic deletions compared to smooth-type Brucella species combined with its rough lipopolysaccharide phenotype and range of dog hosts (Guzmán et al., 2024). Genomic analysis of Bartonella species obtained from domestic dogs and wild canids reveals traces of high genome plasticity with mobile genetic elements and secretory machineries allowing for host adaptation and immune evasion, verifying them as long-term reservoirs. 2.3 Parasitic and fungal pathogens Fungal and parasitic infections are the prevalent form of zoonoses underestimated in canids of the wild and dogs. Toxoplasma gondii, which is primarily disseminated by felids, may infect canids as an intermediate host, and
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