干扰素是脊椎动物抗病毒免疫系统的关键因子。干扰素家族包括I型、II型和III型干扰素。在爬行类,鸟类和哺乳类中,I型和III型干扰素的结构和功能极为相似,但它们需要与不同受体的结合,且在基因结构上具有明显的差异。
I型干扰素基因不含内含子,III型干扰素基因则具有4个内含子。近年来在低等脊椎动物鱼类中发现的干扰素基因具有与III型干扰素相同的基因结构,但是氨基酸序列和功能方面则类似于I型干扰素。鱼类的干扰素基因是属于I型还是III型干扰素,以及I型和III型干扰素基因在脊椎动物中的分化是在该领域研究中的受到关注的问题之一。
在中国科学院水生生物研究所聂品研究员和苏格兰鱼类免疫研究中心邹钧博士的联合指导下,齐志涛博士通过对脊椎动物基因组进行分析,结合基因功能研究,发现两栖动物蟾蜍中同时具有功能性的含有内含子的I型和III型干扰素基因,证实它们在逆转座进化事件以前就已经分化,提出了“逆转座事件发生在脊椎动物由水生转向陆生环境的过渡时期,这一事件造成爬行类、鸟类和哺乳类中I型干扰素基因内含子的丢失”的学术观点。
这一研究成果为全面揭示干扰素系统的演化提供了关键的信息,相关研究结果发表在The Journal of Immunology 。>
生物谷推荐原文出处:
The Journal of Immunology doi:10.4049/jimmunol.0903374
Intron-Containing Type I and Type III IFN Coexist in Amphibians: Refuting the Concept That a Retroposition Event Gave Rise to Type I IFNs
Zhitao Qi,*, Pin Nie,* Chris J. Secombes, and Jun Zou
*State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei; Chemical and Biological Engineering College, Yancheng Institute of Technology, Jiangsu, China; and Scottish Fish Immunology Research Centre, Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, United Kingdom
Type I and III IFNs are structurally related cytokines with similar antiviral functions. They have different genomic organizations and bind to distinct receptor complexes. It has been vigorously debated whether the recently identified intron containing IFN genes in fish and amphibians belong to the type I or III IFN family or diverged from a common ancestral gene, that subsequently gave rise to both types. In this report, we have identified intron containing type III IFN genes that are tandemly linked in the Xenopus tropicalis genome and hence demonstrate for the first time that intron containing type I and III genes diverged relatively early in vertebrate evolution, and at least by the appearance of early tetrapods, a transition period when vertebrates migrated from an aquatic environment to land. Our data also suggest that the intronless type I IFN genes seen in reptiles, birds, and mammals have originated from a type I IFN transcript via a retroposition event that led to the disappearance of intron-containing type I IFN genes in modern vertebrates. In vivo and in vitro studies in this paper show that the Xenopus type III IFNs and their cognate receptor are ubiquitously expressed in tissues and primary splenocytes and can be upregulated by stimulation with synthetic double-stranded RNA, suggesting they are involved in antiviral defense in amphibians.