Krause Christopher D, Pestka Sidney
Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
Pharmacol Ther. 2005 Jun;106(3):299-346. doi: 10.1016/j.pharmthera.2004.12.002. Epub 2005 Apr 14.
The sequencing of a wide variety of genomes and their transcripts has allowed researchers to determine how proteins or protein families evolved and how strongly during evolution a protein has been conserved. In this report, we analyze the evolution of the Class 2 ligands and their cognate receptors by analyzing Class 2 ligand and receptor chain gene sequences from a variety of DNA sequence databases. Both the Class 2 cytokines and receptor chains appear to have developed during the evolution of the chordate phyla: distant homologues of type I interferon (IFN) receptors are the only Class 2 cytokine receptors identified in the Ciona genomes, while a wide variety of Class 2 ligands and receptor chains are encoded in the currently available genomes of bony vertebrates (teleost fish, amphibians, reptiles, birds, mammals). Phylogenetic trees of ligands and ligand-binding receptor chains demonstrate that proteins involved in conferring antiviral activity diverged before those involved in adaptive immunity. Genes encoding IFNs and IFN receptors duplicated multiple times during chordate evolution, suggesting that duplication of genes encoding IFN activity conveyed an evolutionary advantage. Altogether, these data support a model whereby the original Class 2 cytokines and receptors evolved and duplicated during the evolution of the chordate innate immune response system; new receptor and ligand duplications evolved into signaling molecules to fulfill communication requirements of a highly specialized and differentiated vertebrate immune system. In addition, the genomic analysis led to the discovery of some new members of this family.
对多种基因组及其转录本进行测序，使研究人员能够确定蛋白质或蛋白质家族是如何进化的，以及在进化过程中一种蛋白质的保守程度如何。在本报告中，我们通过分析来自各种DNA序列数据库的2类配体和受体链基因序列，来分析2类配体及其同源受体的进化。2类细胞因子和受体链似乎都是在脊索动物门的进化过程中产生的：I型干扰素（IFN）受体的远亲同源物是在海鞘基因组中鉴定出的唯一2类细胞因子受体，而在目前可用的硬骨脊椎动物（硬骨鱼、两栖动物、爬行动物、鸟类、哺乳动物）基因组中编码了多种2类配体和受体链。配体和配体结合受体链的系统发育树表明，参与赋予抗病毒活性的蛋白质在参与适应性免疫的蛋白质之前就发生了分化。在脊索动物进化过程中，编码IFN和IFN受体的基因多次复制，这表明编码IFN活性的基因复制传递了一种进化优势。总之，这些数据支持了一个模型，即最初的2类细胞因子和受体在脊索动物先天免疫反应系统的进化过程中进化并复制；新的受体和配体复制进化为信号分子，以满足高度专业化和分化的脊椎动物免疫系统的通讯需求。此外，基因组分析还发现了该家族的一些新成员。
