Abstract:Species differences in the structure and function of the immune system of laboratory animals are known to exist and have been reviewed extensively. However, the number and diversity of wild and exotic species, along with their associated viruses, that come into contact with humans has increased worldwide sometimes with lethal consequences. Far less is known about the immunobiology of these exotic and wild species. Data suggest that species differences of the mechanisms of inflammation, innate immunity and adap… Show more
“…A similar hypothesis can be drawn regarding genes related to skin protection against external dangers (i.e., microbial infection)—the gasdermin family, responsible for host defense and cell death (Tamura and Shiroishi 2015 ). In effect, pangolins display an innate immune gene repertoire that is strikingly variable as compared to other mammalian lineages (Haley 2022 ), and events of pseudogenization have been described for various genes (e.g., viral DNA sensors cGAS and STING; Fisher et al 2020 ). Fig.…”
The mammalian skin exhibits a rich spectrum of evolutionary adaptations. The pilosebaceous unit, composed of the hair shaft, follicle, and the sebaceous gland, is the most striking synapomorphy. The evolutionary diversification of mammals across different ecological niches was paralleled by the appearance of an ample variety of skin modifications. Pangolins, order Pholidota, exhibit keratin-derived scales, one of the most iconic skin appendages. This formidable armor is intended to serve as a deterrent against predators. Surprisingly, while pangolins have hair on their abdomens, the occurrence of sebaceous and sweat glands is contentious. Here, we explore various molecular modules of skin physiology in four pangolin genomes, including that of sebum production. We show that genes driving wax monoester formation, Awat1/2, show patterns of inactivation in the stem pangolin branch, while the triacylglycerol synthesis gene Dgat2l6 seems independently eroded in the African and Asian clades. In contrast, Elovl3 implicated in the formation of specific neutral lipids required for skin barrier function is intact and expressed in the pangolin skin. An extended comparative analysis shows that genes involved in skin pathogen defense and structural integrity of keratinocyte layers also show inactivating mutations: associated with both ancestral and independent pseudogenization events. Finally, we deduce that the suggested absence of sweat glands is not paralleled by the inactivation of the ATP-binding cassette transporter Abcc11, as previously described in Cetacea. Our findings reveal the sophisticated and complex history of gene retention and loss as key mechanisms in the evolution of the highly modified mammalian skin phenotypes.
“…A similar hypothesis can be drawn regarding genes related to skin protection against external dangers (i.e., microbial infection)—the gasdermin family, responsible for host defense and cell death (Tamura and Shiroishi 2015 ). In effect, pangolins display an innate immune gene repertoire that is strikingly variable as compared to other mammalian lineages (Haley 2022 ), and events of pseudogenization have been described for various genes (e.g., viral DNA sensors cGAS and STING; Fisher et al 2020 ). Fig.…”
The mammalian skin exhibits a rich spectrum of evolutionary adaptations. The pilosebaceous unit, composed of the hair shaft, follicle, and the sebaceous gland, is the most striking synapomorphy. The evolutionary diversification of mammals across different ecological niches was paralleled by the appearance of an ample variety of skin modifications. Pangolins, order Pholidota, exhibit keratin-derived scales, one of the most iconic skin appendages. This formidable armor is intended to serve as a deterrent against predators. Surprisingly, while pangolins have hair on their abdomens, the occurrence of sebaceous and sweat glands is contentious. Here, we explore various molecular modules of skin physiology in four pangolin genomes, including that of sebum production. We show that genes driving wax monoester formation, Awat1/2, show patterns of inactivation in the stem pangolin branch, while the triacylglycerol synthesis gene Dgat2l6 seems independently eroded in the African and Asian clades. In contrast, Elovl3 implicated in the formation of specific neutral lipids required for skin barrier function is intact and expressed in the pangolin skin. An extended comparative analysis shows that genes involved in skin pathogen defense and structural integrity of keratinocyte layers also show inactivating mutations: associated with both ancestral and independent pseudogenization events. Finally, we deduce that the suggested absence of sweat glands is not paralleled by the inactivation of the ATP-binding cassette transporter Abcc11, as previously described in Cetacea. Our findings reveal the sophisticated and complex history of gene retention and loss as key mechanisms in the evolution of the highly modified mammalian skin phenotypes.
“…Pangolins, when compared to other mammals, display significant changes in innate immune gene repertoires due to pseudogenization events (Fischer et al. 2020a,b; Haley 2022; Pinto et al. 2023).…”
Pangolins (Pholidota, Manidae) are classified as an evolutionarily distinct and globally endangered mammal due to their unique morphology (nail‐like scales and a myrmecophagous diet) and being the victim of heavy poaching and worldwide trafficking. As such, pangolins serve as a textbook example for studying the special phenotypic evolutionary adaptations and conservation genetics of an endangered species. Recent years have demonstrated significant advancements in the fields of molecular genetics and genomics, which have translated to a series of important research achievements and breakthroughs concerning the evolution and conservation genetics of pangolins. This review comprehensively presents the hitherto advances in phylogeny, adaptive evolution, conservation genetics, and conservation genomics that are related to pangolins, which will provide an ample understanding of their diversity, molecular adaptation mechanisms, and evolutionary potentials. In addition, we highlight the priority of investigating species/population diversity among pangolins and suggest several avenues of research that are highly relevant for future pangolin conservation.
“…Comparative genomic studies have revealed a high diversity of innate immune genes in mammals with striking cases of gene degeneration in bats and pangolins [ 22 , 23 , 24 , 25 , 26 ]. Genes involved in the sensing of cytoplasmic DNA, such as CGAS and STING1 , and cytoplasmic RNA, such as IFIH1 /MDA5 and ZBP1 , have been lost during the evolution of pangolins [ 23 , 24 ].…”
One of the main mechanisms of inducing an antiviral response depends on 2′-5′-oligoadenylate synthetases (OAS), which sense double-stranded RNA in the cytoplasm and activate RNase L. Mutations leading to the loss of functional OAS1 and OAS2 genes have been identified as important modifiers of the human immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we performed comparative genomics to search for inactivating mutations of OAS genes in other species of mammals and to establish a model for the diversifying evolution of the OAS gene family. We found that a recombination of the OAS and OAS-like (OASL) loci has led to the loss of OAS2 in camelids, which also lack OAS3. Both paralogs of OASL and OAS3 are absent in Asian pangolins. An evolutionarily ancient OAS paralog, which we tentatively name OAS4, has been lost in pangolins, bats and humans. A previously unknown OAS gene, tentatively named OAS5, is present in Yangochiroptera, a suborder of bats. These differences in the OAS gene repertoire may affect innate immune responses to coronaviruses and other RNA viruses.
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