Woelk Christopher H, Frost Simon D W, Richman Douglas D, Higley Prentice E, Kosakovsky Pond Sergei L
Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA.
Gene. 2007 Aug 1;397(1-2):38-50. doi: 10.1016/j.gene.2007.03.018. Epub 2007 Apr 3.
Interferon alpha (IFNA) genes code for proteins with important signaling roles during the innate immune response. Phylogenetically, IFNA family members in eutherians (placental mammals) cluster together in a species-specific manner except for closely related species (i.e. Homo sapiens and Pan troglodytes) where gene-specific clustering is evident. Previous research has been unable to clarify whether gene conversion or recent gene duplication accounts for gene-specific clustering, partly because the similarity of members of the IFNA family within species has made it historically difficult to identify the exact composition of IFNA gene families. IFNA gene families were fully characterized in recently available genomes from Canis familiaris, Macaca mulatta, P. troglodytes and Rattus norvegicus, and combined with previously characterized IFNA gene families from H. sapiens and Mus musculus, for the analysis of both whole and partial gene conversion events using a variety of statistical methods. Gene conversion was inferred in every eutherian species analyzed and comparison of the IFNA gene family locus between primate species revealed independent gene duplication in M. mulatta. Thus, both gene conversion and gene duplication have shaped the evolution of the IFNA gene family in eutherian species. Scenarios may be envisaged whereby the increased production of a specific IFN-alpha protein would be beneficial against a particular pathogenic infection. Gene conversion, similar to duplication, provides a mechanism by which the protein product of a specific IFNA gene can be increased.
α干扰素(IFNA)基因编码的蛋白质在先天性免疫反应中具有重要的信号传导作用。在系统发育上,真兽亚纲(胎盘哺乳动物)中的IFNA家族成员以物种特异性的方式聚集在一起,但关系密切的物种(即智人和黑猩猩)除外,在这些物种中基因特异性聚集很明显。先前的研究无法阐明基因转换或近期基因复制是否导致了基因特异性聚集,部分原因是物种内IFNA家族成员的相似性使得历史上难以确定IFNA基因家族的确切组成。IFNA基因家族在最近获得的犬、猕猴、黑猩猩和大鼠的基因组中得到了充分表征,并与先前表征的智人和小鼠的IFNA基因家族相结合,使用各种统计方法分析全基因和部分基因转换事件。在分析的每个真兽亚纲物种中都推断出了基因转换,灵长类物种之间IFNA基因家族位点的比较揭示了猕猴中的独立基因复制。因此,基因转换和基因复制都塑造了真兽亚纲物种中IFNA基因家族的进化。可以设想这样的情况,即特定α干扰素蛋白产量的增加对特定的病原体感染可能是有益的。与基因复制类似,基因转换提供了一种增加特定IFNA基因蛋白质产物的机制。