Department of Migration, Max Planck Institute of Animal Behavior, Radolfzell, Germany.
Department of Biology, University of Konstanz, Konstanz, Germany.
Mol Biol Evol. 2022 Aug 3;39(8). doi: 10.1093/molbev/msac160.
Animal species differ considerably in their ability to fight off infections. Finding the genetic basis of these differences is not easy, as the immune response is comprised of a complex network of proteins that interact with one another to defend the body against infection. Here, we used population- and comparative genomics to study the evolutionary forces acting on the innate immune system in natural hosts of the avian influenza virus (AIV). For this purpose, we used a combination of hybrid capture, next- generation sequencing and published genomes to examine genetic diversity, divergence, and signatures of selection in 127 innate immune genes at a micro- and macroevolutionary time scale in 26 species of waterfowl. We show across multiple immune pathways (AIV-, toll-like-, and RIG-I -like receptors signalling pathways) that genes involved genes in pathogen detection (i.e., toll-like receptors) and direct pathogen inhibition (i.e., antimicrobial peptides and interferon-stimulated genes), as well as host proteins targeted by viral antagonist proteins (i.e., mitochondrial antiviral-signaling protein, [MAVS]) are more likely to be polymorphic, genetically divergent, and under positive selection than other innate immune genes. Our results demonstrate that selective forces vary across innate immune signaling signalling pathways in waterfowl, and we present candidate genes that may contribute to differences in susceptibility and resistance to infectious diseases in wild birds, and that may be manipulated by viruses. Our findings improve our understanding of the interplay between host genetics and pathogens, and offer the opportunity for new insights into pathogenesis and potential drug targets.
动物物种在抵御感染的能力上有很大差异。要找到这些差异的遗传基础并不容易，因为免疫反应是由一系列相互作用的蛋白质组成的复杂网络，以保护身体免受感染。在这里，我们使用群体和比较基因组学来研究在禽流感病毒（AIV）的自然宿主中先天免疫系统的进化力量。为此，我们使用杂交捕获、下一代测序和已发表的基因组的组合，在 26 种水禽中，在微观和宏观进化时间尺度上，检查了 127 个先天免疫基因的遗传多样性、分化和选择特征。我们跨越多个免疫途径（AIV-、toll 样受体-和 RIG-I 样受体信号途径）表明，参与病原体检测的基因（即 toll 样受体）和直接病原体抑制（即抗菌肽和干扰素刺激基因），以及宿主蛋白被病毒拮抗剂蛋白（即线粒体抗病毒信号蛋白，[MAVS]）靶向的基因比其他先天免疫基因更容易多态、遗传分化和受到正选择。我们的研究结果表明，选择压力在水禽的先天免疫信号通路中是不同的，我们提出了候选基因，这些基因可能导致野生鸟类对传染病的易感性和抵抗力的差异，并且可能被病毒操纵。我们的研究结果提高了我们对宿主遗传学和病原体之间相互作用的理解，并为发病机制和潜在药物靶点提供了新的见解。
