Abstract:
The innate immune system of mammals is formed by a complex web of interacting proteins, which together constitute the first barrier of entry for infectious pathogens. Genes from the E3-ubiquitin ligase tripartite motif (TRIM) family have been shown to play an important role in the innate immune system by restricting the activity of different retrovirus species. For example, TRIM5 and TRIM22 have both been associated with HIV restriction and are regarded as crucial parts of the antiretroviral machinery of mammals. Our analyses of positive selection corroborate the great significance of these genes for some groups of mammals. However, we also show that many species lack TRIM5 and TRIM22 altogether. By analyzing a large number of mammalian genomes, here we provide the first comprehensive view of the evolution of these genes in eutherians, showcasing that the pattern of accumulation of TRIM genes has been dissimilar across mammalian orders. Our data suggest that these differences are caused by the evolutionary plasticity of the immune system of eutherians, which have adapted to use different strategies to combat retrovirus infections. Altogether, our results provide insights into the dissimilar evolution of a representative family of restriction factors, highlighting an example of adaptive and idiosyncratic evolution in the innate immune system.
摘要:
哺乳动物的先天免疫系统是由相互作用的蛋白质组成的复杂网络,它们共同构成了传染性病原体进入的第一道屏障。E3-泛素连接酶三方基序(TRIM)家族的基因已被证明通过限制不同逆转录病毒物种的活性在先天免疫系统中起重要作用。例如,TRIM5和TRIM22都与HIV限制有关,被认为是哺乳动物抗逆转录病毒机制的关键部分。我们对正选择的分析证实了这些基因对某些哺乳动物群体的重大意义。然而,我们还表明,许多物种完全缺乏TRIM5和TRIM22。通过分析大量的哺乳动物基因组,在这里,我们提供了这些基因在异教徒中进化的第一个全面观点,显示TRIM基因的积累模式在哺乳动物中不同。我们的数据表明,这些差异是由异教徒免疫系统的进化可塑性引起的,他们已经适应了使用不同的策略来对抗逆转录病毒感染。总之,我们的结果提供了对代表性限制因子家族的不同进化的见解,突出了先天免疫系统适应性和特质进化的一个例子。