International Journal of Molecular Veterinary Research 2025, Vol.15, No.1 http://animalscipublisher.com/index.php/ijmvr © 2025 AnimalSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved.
International Journal of Molecular Veterinary Research 2025, Vol.15, No.1 http://animalscipublisher.com/index.php/ijmvr © 2025 AnimalSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Publisher AnimalSci Publisher Editedby Editorial Team of International Journal of Molecular Veterinary Research Email: edit@ijmvr.animalscipublisher.com Website: http://animalscipublisher.com/index.php/ijmvr Address: 11388 Stevenston Hwy, PO Box 96016, Richmond, V7A 5J5, British Columbia Canada International Journal of Molecular Veterinary Research (ISSN 1927-5331) is an open access, peer reviewed journal published online by AnimalSci Publisher. The journal is publishing all the latest and outstanding research articles, letters and reviews in all aspects of molecular veterinary research, containing diseases and disease vectors of livestock and wildlife around the world, the epidemiology, diagnosis, case report, prevention and treatment of medical conditions of domestic at molecular level, as well as the biomedical procedures that based on their health. Meanwhile we also publish the articles related to basic research, such as anatomy and histology, which are fundamental to molecular technique’s innovation and development. AnimalSci Publisher is an international Open Access publisher specializing in animal science, and veterinary-related research registered at the publishing platform that is operated by Sophia Publishing Group (SPG), founded in British Columbia of Canada. All the articles published in International Journal of Molecular Veterinary Research are Open Access, and are distributed 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. AnimalSci Publisher uses CrossCheck service to identify academic plagiarism through the world’s leading plagiarism prevention tool, iParadigms, and to protect the original authors’ copyrights.
International Journal of Molecular Veterinary Research (online), 2025, Vol. 15, No.1 ISSN 1927-5331 http://animalscipublisher.com/index.php/ijmvr © 2025 AnimalSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Latest Content The Evolution of Immune System Genes in Canids: A Comparative Genomic Approach Xuezhong Zhang, Jun Wang International Journal of Molecular Veterinary Research, 2025, Vol. 15, No. 1, 1-12 Genomic Selection for Disease Resistance in Chickens and Its Application in Poultry Breeding Jing He, Xiaofang Lin International Journal of Molecular Veterinary Research, 2025, Vol. 15, No. 1, 13-21 Comparative Genomics of Zoonotic Pathogens in Domestic Dogs and Their Wild Relatives Xinghao Li, Shiqiang Huang International Journal of Molecular Veterinary Research, 2025, Vol. 15, No. 1, 22-31 Pathogenesis and Molecular Diagnosis of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Hui Liu, Jia Xuan International Journal of Molecular Veterinary Research, 2025, Vol. 15, No. 1, 32-42 Genetic Diversity and Selection of Disease-Resistant Tilapia Strains Linhua Zhang, Fan Wang International Journal of Molecular Veterinary Research, 2025, Vol. 15, No. 1, 43-50
International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 1-12 http://animalscipublisher.com/index.php/ijmvr 1 Feature Review Open Access The Evolution of Immune System Genes in Canids: A Comparative Genomic Approach Xuezhong Zhang1 , JunWang2 1 Tropical Animal Medicine Research Center, Hainan Institute of Tropical Agricultural Resources, Sanya, 572025, Hainan, China 2 Animal Science Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: xuezhong.zhang@hitar.org International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1 doi: 10.5376/ijmvr.2025.15.0001 Received: 10 Dec., 2024 Accepted: 15 Jan., 2025 Published: 25 Jan., 2025 Copyright © 2025 Zhang and Wang, 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: Zhang X.Z., and Wang J., 2025, The evolution of immune system genes in canids: a comparative genomic approach, International Journal of Molecular Veterinary Research, 15(1): 1-12 (doi: 10.5376/ijmvr.2025.15.0001) Abstract The Canidae family, which includes species such as wolves, foxes, and domestic dogs, inhabits diverse ecological environments and faces a wide range of pathogenic threats. This study employs a comparative genomics approach to explore the genetic diversity, evolutionary trajectories, and functional adaptations of immune genes in canids. It focuses on the structure and function of innate and adaptive immune genes, and on the roles of natural selection, gene duplication, and horizontal gene transfer in shaping the immune gene repertoire, as well as the unique adaptations found in wild and domesticated canids. Advances in next-generation sequencing technology have facilitated the identification and classification of immune genes, revealing mechanisms that are both conserved across mammalian lineages and species-specific. Special emphasis is placed on the critical role of the major histocompatibility complex (MHC) in pathogen recognition and its implications for disease resistance and species conservation. This study holds significant value for understanding mammalian immunity, informing conservation strategies, and guiding the development of veterinary interventions aimed at enhancing pathogen resistance in both wild and domesticated canids. Keywords Immune system evolution; Comparative genomics; Major histocompatibility complex (MHC); Pathogen pressure; Canid adaptation 1 Introduction The Canidae family, with the wolves, foxes, and domestic dog among its members, is an integral part of numerous ecosystems as predators, scavengers, and even human companions. They lead several lives and inhabit various spaces, and thus they are exposed to a multitude of pathogens, and they need to have a robust and adaptable immune system (Bartocillo et al., 2021). These pathogens have exerted evolutionary pressures that have resulted in extensive diversification of the immune genes within canids, and canids thus form a suitable group within which to examine the evolution of the immune system (Vinkler et al., 2023). Raccoon dog MHC genes involve high allelic diversity through pathogen-driven selection, recombination, and long-lasting balancing selection (Bartocillo et al., 2021). Immunogenes, particularly pathogen recognition and response genes, are under intense selective pressures (Larragy et al., 2023). Gene evolution of immune systems is important to the survival and adaptation of raccoon dogs in environments. The gene diversity enhances the efficiency of canids in distinguishing and resisting broad types of pathogens and their fitness and survival (Bradshaw and Valenzano, 2020; Vinkler et al., 2023). The purpose of this study is to research the history of dog immune genes deeply by comparative genomics approaches. According to genetic variation analysis, evolutionary history, and functional constraint of immune genes, this study tries to explore the molecular mechanism of dog immune adaptation. This study will touch on various features, from the discovery of immune genes to selection pressures acting on them and the role of some pathogens on their evolution. Keeping this in mind, we think we shall be more aware of the evolutionary processes of canine immunity and its role in resistance to disease as well as ecological adaptation.
International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 1-12 http://animalscipublisher.com/index.php/ijmvr 2 2 Structure and Function of Immune System Genes in Mammals 2.1 Key immune system components and pathways Mammalian immune responses are made up of two major components: innate and adaptive immunity. Innate immunity is the first line of defense against pathogens and employs pattern recognition receptors (PRRs) such as toll-like receptors (TLRs) to recognize pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) (Nie et al., 2018). TLRs are some of the most conserved and oldest of the PRRs and play a crucial role in initiating immune responses across a wide variety of species, from invertebrates to mammals (Nie et al., 2018). The adaptive immune system is distinguished by its ability to generate a clonally diverse population of lymphocytes, each having unique antigen receptors. This mechanism was evolved in vertebrate ancestors and provides an advantage of survival by enabling the identification and rejection of pathogen intruders through recombinatorial shuffling of immunoglobulin or T cell receptor gene segments (Cooper and Alder, 2006). 2.2 Classification of immune genes: innate vs. adaptive Immune genes may be broadly classified into those that operate in the innate and the adaptive immune systems. The innate immune genes are those that code for PRRs like TLRs to directly cause pathogen recognition and downstream signaling cascades (Nie et al., 2018). The genes are conserved among species, indicative of their critical role in immune defense. Adaptive immune genes do create diverse antigen receptors, though, by processes such as V(D)J recombination in jawed vertebrates or leucine-rich-repeat genetic module assembly in jawless vertebrates like lampreys and hagfish (Cooper and Alder, 2006). The dualism highlights the innovation that has developed in order to allow vertebrates to construct sophisticated pathogen recognition and response mechanisms. 2.3 Comparison of immune gene function across mammals The function of immune genes is varied across different mammalian species and reflects both conserved processes as well as species-specific evolution. TLRs, for instance, have similar domain structure and signaling pathways in organisms as varied as mammals (Nie et al., 2018). However, functional diversification and evolution of new signaling pathways and adaptors has occurred, leading to variations in immune response across different species (Nie et al., 2018). In the adaptive immune system, jawed vertebrates have conserved mechanisms for creating diversity of antigen receptors, but they could be different with regard to distinct genetic changes and pathways. For example, even though all jawed vertebrates use recombinatorial rearrangement of T cell receptor or immunoglobulin gene segments, jawless vertebrates like lampreys and hagfish possess a different system using leucine-rich-repeat genetic modules (Cooper and Alder, 2006). These differences unveil the evolutionary diversity and imagination in immune gene function across mammals. 3 Genomic Advances in Studying Canid Immunity 3.1 Sequencing and annotation of canid genomes Evolution of next-generation sequencing (NGS) technologies has revolutionized canid genome studies with the ability to perform high-throughput sequencing and detailed annotation of genetic information. The technologies enabled sequencing a number of species of canids and provide immense amounts of genomic data that may be used to examine the genetic basis of immune response. For instance, NGS has been central in annotating and identifying immune genes in different species so that scientists can compare and gain insights on the evolutionary dynamics of the immune genes (Clark and Greenwood, 2016). The application of NGS in model organisms, such as canids, has also hinted at the challenges in gene annotation, particularly for rapidly evolving immune genes that may not be well captured in available databases. 3.2 Identification and cataloging of immune genes Canid immune gene characterization and classification have also been significantly facilitated by comparative transcriptomics and genomics. Comparative approaches have enabled immune gene repertoires in various species to be revealed with hints of conserved and divergent immune aspects. For clarification, it has already been shown in studies that genes that are involved in the recognition of pathogens and direct pathogen inhibition are under
International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 1-12 http://animalscipublisher.com/index.php/ijmvr 3 positive selection, that is, these are involved in defending the host (Figure 1) (Jax et al., 2022). In addition, RNA-seq application has made it possible for infection-regulated transcriptomes to be extensively explored and has provided insight into the differential immune response mounted by various pathogens (Sackton, 2019). All this extensive cataloging of immune genes is required so that canid immunologic molecular mechanisms may be unraveled and their evolutionary history understood. Figure 1 Ratio of nonsynonymous to synonymous changes (dN/dS) mapped on the Toll-like receptor signaling pathway from the KEGG database (Kanehisa 2019; Kanehisa and Goto 2000; Kanehisa et al. 2021). Each box represents one gene in the pathway and the color within the box shows dN/dS for that particular gene. dN/dS was estimated from a total of 26 species of waterfowl using PAML. Small boxes without a color indication were not included in the hybrid capture, usually because they were not annotated in the mallard genome at the start of the study (Adopted from Jax et al., 2022) 3.3 Limitations and challenges in canid genomics Despite the huge advances in canid genomics, challenges and limitations remain. One among them is the quality and completeness of genomic data, which may be undermined by errors in sequencing and gaps in genome assemblies (Sackton, 2020). In addition, immune gene annotation tends to be complicated because of their rapid evolutionary rate and the prevalence of species-specific adaptations, thus leading to incomplete or erroneous annotations (Clark and Greenwood, 2016). A further complication is that additional, larger population resequencing data are required to fully resolve the evolutionary pressures acting on immune genes and uncover rare variants with potentially significant roles in immunity (Sackton, 2020). These challenges will be met by the application of increasingly sophisticated bioinformatic software and the generation of high-quality genomic data from a broader array of canid species. 4 Evolutionary Mechanisms Shaping Immune Genes 4.1 Natural selection and immune gene variability Natural selection is also a significant force that drives canid immune gene diversity. Positive selection, in particular, has been identified as one of the key forces shaping the evolution of immune system genes in species. For instance, it is already established by research that immunity genes and pathogen recognition genes, such as the major histocompatibility complex (MHC) genes, experience diversifying selection of high intensity since they are engaged in host-pathogen interactions (Fornůsková et al., 2013; Dearborn et al., 2022). This selective pressure
International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 1-12 http://animalscipublisher.com/index.php/ijmvr 4 renders the rates of polymorphism high, which increases the immune system's capacity to identify and react to an extensive range of pathogens (Dearborn et al., 2022). Additionally, balanced polymorphisms, whereby several alleles are maintained in a population, have been identified in immune-related genes, elevating the degree of genetic diversity and adaptability (Rottschaeffer et al., 2014). 4.2 Gene duplication and diversification in canids Gene duplication is another important process that has been responsible for diversification of immune genes in canids. Gene duplication may lead to the creation of gene families with multiple copies, each of which may develop new functions or become specialized in a different function of immunity. For example, MHC class I and II genes are extensively duplicated and diversified, which results in an extensive array of alleles that expand immunity recognition abilities (Kiemnec-Tyburczy et al., 2012; Dearborn et al., 2022). It is not limited to MHC genes; other immune genes, such as those coded for in the Toll-like receptor (TLR) pathways, also demonstrate signs of duplication followed by functional diversification (Fornůsková et al., 2013). These duplications allow for the generation of novel immune functions and improvement of immune responses to specific pathogens. 4.3 Horizontal gene transfer and immune system evolution Horizontal gene transfer (HGT) has been discovered to be a major force in the evolution of the immune system, including in canids. HGT involves the passing of genetic material from one species to another, where it can introduce new genes and functions to a genome. This has been particularly seen in the example of microbial and viral interactions, where immune-supportive genes can be received from the external environment (Marchalonis and Schluter, 1998; Lawrence, 1999). For instance, the rapid evolution of phylogenetically specialized immune responses in vertebrates has been explained by horizontal transfers of recombination signal sequences and site-specific recombinases from bacterial sources, which facilitated the evolution of sophisticated immune gene repertoires (Marchalonis and Schluter, 1998). Such events are able to cause profound evolutionary change, providing adaptive advantage simultaneously in the face of new or rising pathogens. 5 Immune System Adaptations in Wild Canids 5.1 Immune challenges in wolves and coyotes Wolves and coyotes are subjected to a variety of immune challenges in the wild, prompted by their exposure to a variety of pathogens. Their canid immune system has developed to optimize defense against pathogens. For instance, molecular characterization of MHC class I genes in a close wolf and coyote relative, the raccoon dog, has high allelic diversity and positive selection due to pathogen pressure, suggesting similar evolutionary pressures in coyotes and wolves (Bartocillo et al., 2021). Additionally, the complex history of introgression and admixture among canids, as witnessed in the case of Himalayan and Tibetan wolves, is used to highlight the role of genetic diversity in immune responses to environmental stresses (Wang et al., 2020). 5.2 Unique immune traits in arctic and desert canids Arctic and desert canids possess unique immune features that reflect their special adaptation for survival in extreme conditions. Tibetan wolves and Himalayan wolves, for example, possess a very high frequency of EPAS1 haplotypes, which confer an adaptive advantage at high elevation by enhanced oxygen delivery and possibly an effect on immunity. Such an adaptation testifies to the role of unique genetic traits in supporting survival in adverse conditions. Similarly, desert canids may have evolved specific immune mechanisms in order to acclimatize to the environment of the desert and desert pathogens, although few direct studies on desert canids exist (Wang et al., 2020) (Figure 2). 5.3 Role of pathogen pressure in shaping immune genes Pathogen pressure represents a strong force in shaping the evolution of canid immune genes. The fact that MHC class I genes in raccoon dogs possess high allelic diversity, driven by pathogen-driven positive selection, recombination, and long-term balancing selection, is an illustration of how pathogen pressure may shape the evolution of immune genes (Bartocillo et al., 2021). This phenomenon would also hold true for other canids, wolves, and coyotes, where frequent exposure to diverse pathogens necessitates a robust and adaptable immune
International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 1-12 http://animalscipublisher.com/index.php/ijmvr 5 system. Co-evolution with pathogens is the pressure for the immunogenetic variation seen among the canid species, optimizing their immune response to the specific pathogens that they are exposed to in their habitat (Vinkler et al., 2023). Figure 2 High-altitude wolves likely carry ancestries from a diverged novel lineage (Adopted from Wang et al., 2020) Image caption: (A) Pairwise FST showed that high-altitude wolf (merging Tibetan wolf and Himalayan wolf) is more diverged with dog than is lowland. In this analysis, ten randomly selected samples for each population were used. Statistical significance was measured by Wilcoxon signed-rank test. (B) Best fitted model (without any f4 outliers) inferred by qpGraph shows that high-altitude wolf could be modeled as a population carrying 39% of ancestry from a diverged lineage that is basal to dog and lowland wolves (one Chinese wolf and one European wolf). African wild dog (AFD) was used as an outgroup. Branch lengths are shown in units of FST × 1,000 and dashed lines indicate inferred admixture events with admixture proportion reported beside the dashed lines. HAWs, high-altitude wolves; LDs, lowland dogs; TDs, Tibetan dogs; LWs, lowland wolves. Because this analysis assumed no gene flow between outgroup and inside population, and dhole and golden jackal have been reported to have gene flow with dog and gray wolf, we selected African wild dog to construct the admixture graph. (C) Neighbor-Joining tree constructed for genomic regions in high-altitude wolf showing of signal of "divergent" origin revealed by HMM with a cutoff of 0.8 posterior probability. Values at nodes indicate support in 1 000 bootstrap analyses (Adopted from Wang et al., 2020) 6 Immune System Genes in Domestic Dogs 6.1 Evolutionary history of domestication and immune function Domestication of dogs from wolf is a process that has taken approximately 32 000 years, and through evidence, it has been suggested that dogs have been under human selection for more than anticipated (Wang et al., 2013). Domestication for so long has caused deep genetic changes, such as those for genes related to the immune system. Domestication has also affected the immune system's ability to cope in diverse environments, including the African tropical environment. As a case in point, African indigenous dogs have developed genetic alterations that enhance their resistance against tropical parasites and encompass genes like ADGRE1, which plays a critical role in mediating protective host defense against infection (Liu et al., 2018).
International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 1-12 http://animalscipublisher.com/index.php/ijmvr 6 6.2 Influence of artificial selection on immune genes Artificial selection has extensively shaped the genetic foundation of the domestic dog, including their genes for the immune system. The intense trait-targeted selection during the process of domestication has led to the forthcoming rebuilding of genomic regulatory element structure and sequence with an eventual impact on immune function (Koch et al., 2016). Copy number variations (CNVs) and structural variations (SVs) have also been recognized as primary determinants of phenotypic variation and disease susceptibility in domestic dogs. For instance, CNVs in immune response gene-related regions have been found to differ largely among breeds, and this differentiation indicates that these parts have been under artificial selection to enhance some immune features (Serres-Armero et al., 2017; 2021). 6.3 Comparative analysis of wild vs. domestic canid immunity Comparative genomic analysis of domestic dogs and their wild counterparts, viz., wolves and raccoon dogs, reveals widespread distinction in immune genes. The personalized structural patterns and methylation observed in domestic dogs are not found in wild canids, and this points to the fact that domestication has led to unique immunogenetic profiles (Koch et al., 2016; Wang et al., 2018). For instance, MHC class I gene research in raccoon dogs demonstrates the extensive allelic diversity under positive pathogen selection, as in domestic dogs, to indicate long-term balancing selection in dogs (Bartocillo et al., 2021). In addition, genomic areas under selection in domestic dogs overlap with areas linked to immune response, reflecting the influence of natural and artificial selection on domestic dog immune systems (Plassais et al., 2019). 7 Comparative Genomics of Canids and Other Mammals 7.1 Insights from comparative studies with non-canid carnivores Comparative genomic investigations with non-canid carnivores have also provided useful insights into the evolution of immune system genes. MHC class I genes in the sable (Martes zibellina), for instance, revealed signs of balancing selection and recombination in their evolution. This study also reported a potential nonclassical MHC class I family in Carnivora that would have existed before the divergence of Caniformia and Feliformia approximately 52~57 million years ago (Zhao et al., 2020). Similarly, comparisons of the Leukocyte Receptor Complex (LRC) of certain of these carnivores, such as felids and mustelids, have shown that LRC structure is relatively conserved in them. However, felids and canids vary to some extent in terms of the LILR gene sub-region, exhibiting different evolutionary histories (Figure 3) (Jelínek et al., 2023). 7.2 Immune gene evolution across carnivoran lineages Immune gene evolution in carnivoran lineages is marked by extensive adaptation and diversity. In raccoon dogs (Nyctereutes procyonoides), the MHC class I genes have wide allelic diversity owing to pathogen-driven positive selection, recombination, and long-term balancing selection. The diversity is an indicator of the high frequency of non-synonymous substitutions and positively selected sites in the MHC class I protein domains (Bartocillo et al., 2021). Additionally, the rapid evolution of HERC6 and the doubling of a rodent- and bat-specific chimeric HERC5/6 gene suggest that the genes have experienced powerful adaptive evolution likely due to genetic arms races with viral pathogens (Jacquet et al., 2020). This rapid evolution is also observed in bats, in which reduction of interferon (IFN)-α genes and enlargement of IFN-ω genes may be contributing to their particular immune responses as well as heightened viral tolerance (Scheben et al., 2023). 7.3 Broader implications for mammalian immunity Comparative genomics between canids and other mammals is of great importance in the understanding of mammalian immunity. The occurrence of conserved and divergent immune gene families in all mammalian lineages indicates the complex evolution of the immune system. For example, the comparison of the opossum immune genome suggests that the increase in mammalian immune system complexity occurred before the marsupial-eutherian divergence, approximately 180 million years ago. This indicates that early mammals likely possessed all large immune gene families and lineage-specific expansion and contraction occurred under fluctuating pathogen pressures (Belov et al., 2007). Further, the evolutionary data gained by host-pathogen
International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 1-12 http://animalscipublisher.com/index.php/ijmvr 7 coevolutionary analysis in mammals could provide insights into the genetic susceptibility to infection and the progression of many diseases (Sironi et al., 2015). Figure 3 Phylogeny of putatively functional LILR genes in Carnivora (Adopted from Jelínek et al., 2023) Image caption: Coding sequences were compared to bovine, caprine, and human LILRs (Supplementary Data 1) by the Neighbor-Joining method and Tamura 3-parameter model in MEGA X. A bootstrap consensus tree is presented with branches reproduced in over 50% of 1000 replicates. The tree was rooted to the novel Ig-like gene sequences. Four Carnivora families are highlighted: Felidae (yellow)-the domestic cat (Felcat), jungle cat (Felcha), Bengal cat (Priben), fishing cat (Priviv), cheetah (Acijub), Geoffroy’s cat (Leogeo), Canada lynx (Lyncan), clouded leopard (Neoneb), lion (Panleo), tiger (Pantig); Canidae (green)-wolf (Canlup), domestic dog (Canfam), dingo (Candin), Tibetan sand fox (Vulfer), arctic fox (Vullag); Mustelidae (brown)-ermine (Muserm), European badger (Melmel), American mink (Neovis), Eurasian otter (Lutlut); and Otariidae (blue)-California sea lion (Zalcal) (Adopted from Jelínek et al., 2023) 8 Genomic Responses to Emerging Pathogens in Canids 8.1 Historical pathogen outbreaks and genomic signatures Historical pathogen outbreaks have left deep genomic signatures in canids, and these are signs of the evolutionary forces exerted by such pathogens. Comparative genomics has shown that immune genes are among the most
International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 1-12 http://animalscipublisher.com/index.php/ijmvr 8 quickly evolving since they are at play in host-pathogen interactions (Sironi et al,. 2015; Sackton, 2019). For instance, the analysis of waterfowl immune systems unveiled genes involved in innate immunity and pathogen recognition and inhibition, such as toll-like receptors and antimicrobial peptides, to often be under positive selection, indicating that they have been significant during past resistance to pathogens (Jax et al., 2022). Similarly, evolutionary history of mammalian immune genes highlights the role of ancient infection in shaping genetic diversity and immune response (Sironi et al., 2015). 8.2 Modern threats: rabies, distemper, and zoonotic diseases New canids are also severely susceptible to rabies, distemper, and other zoonoses. Their quick immune gene evolution to the pathogens has been documented in various scientific studies. In one such study, for example, genomic analysis of the dolphin epidemic as a result of a morbillivirus outbreak isolated several candidate immunity-involving genes indicating the significance of genetic diversity in resisting viral invasion (Batley et al., 2021). In addition, studies on zoonotic pathogens like Bordetella hinzii in immunocompromised animals have shown how pathogens can rapidly adapt to novel hosts and the fluidity of host-pathogen dynamics (Launay et al., 2021). Bat comparative genomes have also revealed special immune adaptations that may be the cause of their reservoir status of zoonotic viruses and illuminated possible mechanisms for pathogen resistance among canids (Tian et al., 2023). 8.3 Potential for genomic monitoring of pathogen resistance The future for genomic monitoring of canid pathogen resistance is bright with the evolution of genomic technology. Whole genome sequencing and comparative genomics can exhibit genetic variation associated with immune response, facilitating surveillance of pathogen resistance through time (Batley et al., 2021). For instance, genomic patterns of immune genes can be employed to track resistance evolution to certain pathogens, as also seen in insect immune genes where fast evolution and positive selection are the rule (Sackton, 2019; Ngo et al., 2022). Moreover, the integration of population genetics and systems immunology can better establish determinants of variation in the immune response such that the conservation strategy can be adapted (Quintana-Murci, 2019). 9 Case Study: Evolution of the Major Histocompatibility Complex (MHC) in Canids 9.1 Overview of the MHC and its role in immune response Major Histocompatibility Complex (MHC) is one of the main components of the vertebrate immune system, with a focus on presenting peptide antigens to T-cells and triggering an adaptive immune response. MHC genes are some of the most polymorphic in the vertebrate genome, with extensive allelic diversity required to be able to recognize a wide variety of pathogens (Kaufman, 2018; Radwan et al., 2020; Abualrous et al., 2021). This polymorphism is maintained by balancing selection pressures such as heterozygote advantage and frequency-dependent selection, which depend on pathogen-mediated forces (Hedrick, 1994; Sommer, 2005; Dearborn et al., 2022). MHC is divided into class I and class II genes, with different roles in immune function. Class I MHC molecules present intracellular antigens, typically viruses, to CD8+ T cells, while class II MHC molecules present extracellular antigens to CD4+ T cells (Kaufman, 2018; Abualrous et al., 2021) (Figure 4). 9.2 Comparative analysis of MHC genes in wolves, coyotes, and dogs Comparative genomic studies have given good insights into the evolution and diversity of MHC genes in canids like wolves (Canis lupus), coyotes (Canis latrans), and domestic dogs (Canis familiaris). These studies have demonstrated that MHC genes in these canids have high polymorphism and are subjected to strong positive selection pressures (Kelley et al., 2004; Lapalombella, 2016; Bartocillo et al., 2021). For instance, research on Italian wolves has reported extensive genetic polymorphism of MHC class II genes that are critical for their survival and fitness to different environments (Lapalombella, 2016). Similarly, research on raccoon dogs, a non-model canid, has reported high allelic polymorphism of MHC class I genes with proof of long-term balancing selection and pathogen-mediated positive selection (Bartocillo et al., 2021). These findings emphasize the importance of MHC polymorphism to provide immune competence and versatility in natural populations.
International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 1-12 http://animalscipublisher.com/index.php/ijmvr 9 Figure 4 Key processes shaping MHC polymorphism in populations and within-individual antigen-binding range (Adopted from Radwan et al., 2020) 9.3 Implications for conservation and disease resistance Genetic variation of the MHC gene plays a significant role in canid population conservation and immunity against disease. Enhanced variability of the MHC has been found to be associated with stronger immune perception and resistance against numerous pathogens, crucial for species survival in nature (Hedrick, 1994; Sommer, 2005; Piertney and Oliver, 2006). Conservation efforts targeting the maintenance of MHC diversity for long-term canid population viability should therefore ensue. But this can be achieved through undertaking activities such as habitat conservation, evasion of human-created genetic bottlenecks, and facilitation of gene exchange across fragmented populations (Sommer, 2005; Lapalombella, 2016). Also, understanding of the MHC gene evolutionary process has been used in the development of breeding programs for enhancing disease resistance in domestic dogs, hence enhancing their longevity and health (Kelley et al., 2004; Bartocillo et al., 2021). 10 Conclusion and Future Directions Canid immune system gene evolution has been influenced by a complex interplay of environmental and genetic pressures. Recent genomic and transcriptomic technologies have illuminated molecular mechanisms underlying the evolutionary process. For instance, the immunome has been suggested to circumscribe immune defense genes within a comparative context, highlighting multi-dimensional selection pressures acting on different classes of immune genes. Comparative genomics revealed an elaborate network of nucleotide-based mechanisms that are key to biological conflict, immunity, and signaling and further indicative of the multi-dimensionality of immune gene evolution. Moreover, the studies of DNA-editing enzymes like activation-induced cytidine deaminase (AID) indicated that the enzymes were key to diversify the antigen receptor genes to combat viral infection. These observations collectively bring our understanding of the evolutionary dynamics between the host and pathogen closer, setting us much better positioned to fully enjoy immune gene evolution in canids.
International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 1-12 http://animalscipublisher.com/index.php/ijmvr 10 Although substantial advances have been achieved, some lingering gaps in the understanding of canid immune gene evolution remain. Such a gap is that there has been largely a lack of focus on evolutionarily divergent species that might provide rich insights into the broad evolutionary trends in immune genes. Additionally, although the genetic basis of interspecies variability in immune responses has been explored, the intricate protein-protein interaction network that defines the immune system is not yet well understood. Further detailed investigations of the macro- and microevolutionary heterogeneity of immune genes are also needed. Technologically, more advanced tools and strategies for probing the real-time conformations and evolutionary time displacements of immune-related proteins are also necessary, which may unveil a more profound insight into their biological roles. These findings of immune gene evolution research in canids also have various possible implications for veterinary medicine and conservation. An understanding of the genetics of the immune response may assist in the design of specific conservation plans for endangered canid populations by the detection of animals with resistant genetic composition against certain pathogens. This data can be employed in veterinary medicine to produce more effective vaccines and therapies for infectious disease in domestic and wildlife canids. The discovery of candidate genes for pathogen recognition and inhibition can also lead to the discovery of new drug targets, which will expand the potential for controlling and treating disease in canid populations. Collectively, additional research in immune gene evolution can improve the well-being and survival of canid species by enlightened veterinary and conservation practice. Acknowledgments We would like to express our sincere gratitude to Ms. Yan from the project team for her thoughtful guidance and strong support, which played a crucial role in the successful progress of this study. Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Abualrous E., Sticht J., and Freund C., 2021, Major histocompatibility complex (MHC) class I and class II proteins: impact of polymorphism on antigen presentation, Current Opinion in Immunology, 70: 95-104. https://doi.org/10.1016/j.coi.2021.04.009 Bartocillo A., Nishita Y., Abramov A., and Masuda R., 2021, Evolution of MHC class I genes in Japanese and Russian raccoon dogs, Nyctereutes procyonoides (Carnivora: Canidae), Mammal Research, 66: 371-383. https://doi.org/10.1007/s13364-021-00561-y Batley K., Sandoval-Castillo J., Kemper C., Zanardo N., Tomo I., Beheregaray L., and Möller L., 2021, Whole genomes reveal multiple candidate genes and pathways involved in the immune response of dolphins to a highly infectious virus, Molecular Ecology, 30: e15873. https://doi.org/10.1111/mec.15873 Belov K., Sanderson C., Deakin J., Wong E., Assange D., McColl K., Gout A., Bono B., Barrow A., Speed T., Trowsdale J., and Papenfuss A., 2007, Characterization of the opossum immune genome provides insights into the evolution of the mammalian immune system, Genome Research, 17(7): 982-991. https://doi.org/10.1101/GR.6121807 Bradshaw W., and Valenzano D., 2020, Extreme genomic volatility characterizes the evolution of the immunoglobulin heavy chain locus in cyprinodontiform fishes, Proceedings of the Royal Society B: Biological Sciences, 287: 20200489. https://doi.org/10.1098/rspb.2020.0489 Clark K., and Greenwood S., 2016, Next-generation sequencing and the crustacean immune system: the need for alternatives in immune gene annotation, Integrative and Comparative Biology, 56(6): 1113-1130. https://doi.org/10.1093/ICB/ICW023 Cooper M., and Alder M., 2006, The evolution of adaptive immune systems, Cell, 124: 815-822. https://doi.org/10.1016/j.cell.2006.02.001 Dearborn D., Warren S., and Hailer F., 2022, Meta-analysis of major histocompatibility complex (MHC) class IIA reveals polymorphism and positive selection in many vertebrate species, Molecular Ecology, 31: 6390-6406. https://doi.org/10.1111/mec.16726 Fornůsková A., Vinkler M., Pagés M., Galan M., Jousselin E., Cerqueira F., Morand S., Charbonnel N., Bryja J., and Cosson J., 2013, Contrasted evolutionary histories of two Toll-like receptors (Tlr4 and Tlr7) in wild rodents (MURINAE), BMC Evolutionary Biology, 13: 194. https://doi.org/10.1186/1471-2148-13-194
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International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 13-21 http://animalscipublisher.com/index.php/ijmvr 13 Research Insight Open Access Genomic Selection for Disease Resistance in Chickens and Its Application in Poultry Breeding JingHe1, Xiaofang Lin2 1 Animal Science Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China 2 Tropical Animal Medicine Research Center, Hainan Institute of Tropical Agricultural Resources, Sanya, 572025, Hainan, China Corresponding author: xiaofang.lin@hitar.org International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1 doi: 10.5376/ijmvr.2025.15.0002 Received: 10 Dec., 2024 Accepted: 16 Jan., 2025 Published: 25 Jan., 2025 Copyright © 2025 He and Lin, 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: He J., and Lin X.F., 2025, Genomic selection for disease resistance in chickens and its application in poultry breeding, International Journal of Molecular Veterinary Research, 15(1): 13-21 (doi: 10.5376/ijmvr.2025.15.0002) Abstract Poultry diseases continue to pose a serious threat to the livestock industry. Traditional disease-resistant breeding methods are limited by selection efficiency and genetic gain. This study expounds the principle, technical approach and practical application of genomic selection (GS) in chicken disease resistance breeding, and explores its advantages in enhancing disease resistance, shortening the breeding cycle, and improving the efficiency of multi-trait improvement. Studies have shown that, GS can integrate whole-genome markers and phenotypic data to predict genomic breeding values (GEBV) of complex disease resistance traits, and has been successfully applied to the improvement of disease resistance in Newcastle disease, avian leukemia and other diseases. By combining case analysis and multi-variety research, the complementarity between GS and traditional selection methods was discovered, indicating its potential in enhancing genetic diversity protection and reducing the use of antibiotics. However, in the implementation of GS, it still faces challenges, such as high cost of phenotypic data and errors, in genotype inference. This study provides a precise, efficient and sustainable development path for disease-resistant chicken breeding, which has certain practical guiding significance. Keywords Chicken; Disease resistance; Genomic selection; Genetic basis; Breeding strategy 1 Introduction Poultry production is a vital component of world animal agriculture, contributing substantially to good quality protein supply and food and economic security and prosperity. The most widely produced poultry species are chicken (Gallus gallus domesticus), and their performance is largely decided by genetic, environment, and management factors. Among these, disease resistance is a significant factor in influencing flock health, survivability, and overall production efficiency. Building disease resistance in chickens is therefore crucial to enhance production stability and economic returns, reduce antibiotics and veterinary reliance (Weng et al., 2020). Certain infectious diseases perennially afflict poultry production. Specifically, Newcastle disease, infectious bronchitis, and Marek's disease cause high morbidity and mortality rates, impaired growth performance, and reduced egg production. Outbreaks of these diseases not only undermine animal welfare but also exact enormous economic costs through lost productivity, increased treatment costs, and trade embargos. Effective management of these diseases requires multi-faceted control measures, including vaccination, biosecurity measures, and genetic improvement of host resistance (Zhou et al., 2024). Traditional breeding techniques for disease resistance are largely based on phenotypic selection and family schemes of breeding. While these have yielded measurable progress, they are handicapped by long generation periods, low precision of selection against multigenic traits, and the predominance of environmental influences on phenotypes. In addition, polygenic control of disease resistance and the presence of low-effect genes limit the effectiveness of conventional selection to realize entirely all available genetic variation, causing a consequent lag in overall genetic advance (Li et al., 2025b).
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