哺乳动物AIM-2样受体(ALR)蛋白结合核酸并启动I型干扰素或炎症小体组装的产生,从而有助于宿主先天免疫。在老鼠身上,Alr基因座在序列和拷贝数水平上具有高度多态性,我们在这里展示了它是基因组中最具活力的区域之一。这个区域内一个快速进化的基因,Ifi207在数百万年前通过基因转换或不等重组事件被引入Mus基因组。Ifi207有一个很大的,独特的重复区域,在Mus物种甚至紧密相关的近交Musmusculus品系之间在序列和长度上有所不同。我们显示IFI207在体内控制鼠白血病病毒(MLV)感染,并且在STING介导的对cGAMP的反应中起作用,dsDNA,DMXXA,MLV。IFI207与STING结合,并且包含其重复区似乎可以稳定STING蛋白。Alr基因座和Ifi207为基因功能的进化创新提供了一个清晰的例子,可能是宿主-病原体共同进化的结果。重要提示红皇后假说预测,病原体与宿主之间的军备竞赛可能会加速双方的进化,因此导致毒力因子和免疫相关蛋白的多样性更高,分别。小鼠中的Alr基因家族在过去的几百万年中经历了快速进化,包括两个新成员的创造,MndaL和Ifi207。特别是Ifi207,变得高度分歧,高度相关的近交系小鼠之间有显著的遗传变化。IFI207蛋白在STING途径中起作用,并通过一种新机制促进抗逆转录病毒抗性。数据表明,在宿主-病原体共同进化的压力下,在动态基因座中,基因家族成员之间的基因转换和重组创造了具有新颖和基本功能的新基因,这些基因在生物过程中发挥着不同的作用。
Mammalian AIM-2-like receptor (ALR) proteins bind nucleic acids and initiate production of type I interferons or inflammasome assembly, thereby contributing to host innate immunity. In mice, the Alr locus is highly polymorphic at the sequence and copy number level, and we show here that it is one of the most dynamic regions of the genome. One rapidly evolving gene within this region, Ifi207, was introduced to the Mus genome by gene conversion or an unequal recombination event a few million years ago. Ifi207 has a large, distinctive repeat region that differs in sequence and length among Mus species and even closely related inbred Mus musculus strains. We show that IFI207 controls murine leukemia virus (MLV) infection in vivo and that it plays a role in the STING-mediated response to cGAMP, dsDNA, DMXXA, and MLV. IFI207 binds to STING, and inclusion of its repeat region appears to stabilize STING protein. The Alr locus and Ifi207 provide a clear example of the evolutionary innovation of gene function, possibly as a result of host-pathogen co-evolution.IMPORTANCEThe Red Queen hypothesis predicts that the arms race between pathogens and the host may accelerate evolution of both sides, and therefore causes higher diversity in virulence factors and immune-related proteins, respectively . The Alr gene family in mice has undergone rapid evolution in the last few million years and includes the creation of two novel members, MndaL and Ifi207. Ifi207, in particular, became highly divergent, with significant genetic changes between highly related inbred mice. IFI207 protein acts in the STING pathway and contributes to anti-retroviral resistance via a novel mechanism. The data show that under the pressure of host-pathogen coevolution in a dynamic locus, gene conversion and recombination between gene family members creates new genes with novel and essential functions that play diverse roles in biological processes.