Krause Christopher D, Pestka Sidney
Department of Biochemistry and Molecular Biology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ, USA; Center for Molecular Biology and Biotechnology, Florida Atlantic University, Boca Raton, FL, USA.
Department of Biochemistry and Molecular Biology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ, USA; PBL Assay Sciences, Piscataway, NJ, USA.
Cytokine. 2015 Dec;76(2):480-495. doi: 10.1016/j.cyto.2015.07.019. Epub 2015 Jul 27.
Interferons (IFNs) are rapidly evolving cytokines released when viral infections are detected in cells. Previous research suggests that genes encoding IFNs and their receptors duplicated extensively throughout vertebrate evolution. We present molecular genetic evidence that supports the use of nonallelic homologous recombination (NAHR) to expand select IFN genes during amniote evolution. The duplication of long regions of genome (encompassing at least one functional IFN gene) followed by the insertion of this genome fragment near its parent's location, is commonly observed in many amniote genomes. Duplicates inserted away from duplication hotspots are not as frequently perturbed with new duplicates, and tend to survive long periods of evolution, sometimes becoming new IFN subtypes. Although most duplicates are inserted parallel to and near the original sequence, the insertion of the Kelch-like 9 gene within the Type I IFN locus of placental mammals promoted antiparallel insertion of gene duplicates between the Kelch-like 9 and IFN-ε loci. Genetic exchange between highly similar Type I gene duplicates as well as between Type III IFN gene duplicates homogenized their diversification. Oddly, Type III IFN genes migrated long distances throughout the genome more frequently than did Type I IFN genes. The inter-chromosomal movement of Type I IFN genes in amniotes correlated with complete intron loss in their gene structure, and repeatedly occurred with occasional Type III IFN genes.
干扰素（IFNs）是细胞在检测到病毒感染时释放的快速进化的细胞因子。先前的研究表明，编码IFN及其受体的基因在整个脊椎动物进化过程中广泛复制。我们提供了分子遗传学证据，支持在羊膜动物进化过程中使用非等位基因同源重组（NAHR）来扩展特定的IFN基因。在许多羊膜动物基因组中普遍观察到基因组的长区域复制（包含至少一个功能性IFN基因），随后该基因组片段插入其亲本位置附近。远离复制热点插入的重复序列不太容易受到新重复序列的干扰，并且倾向于在长时间的进化中存活下来，有时会成为新的IFN亚型。尽管大多数重复序列是与原始序列平行并在其附近插入的，但胎盘哺乳动物I型IFN基因座内的Kelch样9基因的插入促进了基因重复序列在Kelch样9和IFN-ε基因座之间的反平行插入。高度相似的I型基因重复序列之间以及III型IFN基因重复序列之间的基因交换使其多样化趋于一致。奇怪的是，III型IFN基因在整个基因组中远距离迁移的频率比I型IFN基因更高。羊膜动物中I型IFN基因的染色体间移动与其基因结构中内含子的完全丢失相关，并且偶尔会与III型IFN基因一起反复发生。
