International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 22-31 http://animalscipublisher.com/index.php/ijmvr 22 Research Insight Open Access Comparative Genomics of Zoonotic Pathogens in Domestic Dogs and Their Wild Relatives XinghaoLi 1, Shiqiang Huang2 1 Institute of Life Sciences, Jiyang Colloge of Zhejiang A&F University, Zhuji, 311800, Zhejiang, China 2 Tropical Animal Medicine Research Center, Hainan Institute of Tropical Agricultural Resources, Sanya, 572025, Hainan, China Corresponding author: shiqiang.huang.@hitar.org International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1 doi: 10.5376/ijmvr.2025.15.0003 Received: 19 Dec., 2024 Accepted: 27 Jan., 2025 Published: 10 Feb., 2025 Copyright © 2025 Li and Huang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Li X.H., and Huang S.Q., 2025, Comparative genomics of zoonotic pathogens in domestic dogs and their wild relatives, International Journal of Molecular Veterinary Research, 15(1): 22-31 (doi: 10.5376/ijmvr.2025.15.0003) Abstract The domestic dog (Canis lupus familiaris) and its close wild relatives (e.g., the gray wolf, jackal, and coyote) are evolutionarily closely related and ecologically broadly distributed. They are not only major human companion and economic animals and major hosts and agents of transmission for zoonotic pathogens in the world, but also play a central role in the lives of humans. In recent years, benefiting from the speedy development of high-throughput sequencing and comparative genomics, remarkable achievements have been made in characterizing evolutionary properties, host adaptation strategies, and cross-species transmission modes of canine-linked pathogens. Here, the principal types and characteristics of zoonotic pathogens of domestic dogs and their wild counterparts are systematically described, including viruses (e.g., rabies virus, canine distemper virus, coronaviruses), bacteria (e.g., Leptospira spp., Brucella spp., Bartonella spp.), and parasites and fungi (e.g., Toxoplasma gondii, Leishmania spp., Dirofilaria immitis). It places emphasis on the applications of comparative genomics in studying pathogen evolutionary dynamics, core and accessory genome structure, host-specific adaptation, and horizontal gene transfer, and details the molecular mechanisms and risk factors of cross-host transmission. It further compares genomic variation between domestic dogs and their wild relatives in immune gene diversity, receptor recognition pathways, and co-evolutionary interactions. The study also demonstrates the integrative application of multi-omics strategies (genomics, transcriptomics, proteomics, and metabolomics) to study canine pathogen infection and identifies primary research challenges, including sparse coverage of the genome, sampling of wild organisms, host-pathogen interaction model complexity, and the lack of large-scale comparative studies. Overall, comparative genomic characterization of domestic dog and wild ancestor zoonotic pathogens is informative regarding pathogen evolution mechanism and host adaptation, theoretical foundation and data evidence for zoonotic disease surveillance, risk assessment, and prevention under the "One Health" concept. Keywords Domestic dog; Wild relatives; Zoonotic diseases; Comparative genomics; Host adaptation; Cross-species transmission 1 Introduction The domestic dog (Canis lupus familiaris) is a close relative of wild canids such as wolves (Canis lupus), jackals (Canis aureus), and coyotes (Canis latrans). These species all fall within the genus Canis and are characterized by their remarkable genetic, behavioral, and ecological diversity. Domestication of dogs, which is thought to have occurred between 15,000-30,000 years ago, represents one of the most ancient and extreme examples of human-animal coevolution. Despite domestication, domestic dogs retain many of the physiological and immunological features of their wild ancestors that enable them to exist in diverse environments and interact with diverse wildlife and human-associated ecosystems. Wild canids, on the other hand, occupy a broad range of habitats—from forests and grasslands to urban fringes—and do not share overlapping ecological niches with domestic dogs. This close ecological and evolutionary relationship facilitates the possible exchange of pathogens between domestic and wild canids and is a complicating factor in the epidemiology of zoonotic disease. The domestic dog occupies a unique position at the human-animal-environment interface. They have frequent, direct contact with humans and livestock as pet animals, working dogs, and stray dogs, facilitating the transfer of zoonotic pathogens. They are well-established reservoirs or carriers of many zoonotic agents including Rabies virus, Leptospira spp., Brucella canis, Echinococcus granulosus, Leishmania spp., and other coronaviruses. Also,
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