Evolution of the multifaceted eukaryotic akirin gene family.
Evolution of the multifaceted eukaryotic akirin gene family.
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DOI：
10.1186/1471-2148-9-34
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发表时间：
2009-02-06
影响因子：
3.4
通讯作者：
Johnston IA
中科院分区：
文献类型：
--
作者：
Macqueen DJ;Johnston IA
Akirins是形成果蝇和小鼠中保守的先天免疫应答途径的一部分的核蛋白。本研究的目的是探讨Akirin基因结构和蛋白功能在真核生物中的进化。Akirin基因存在于整个后生动物中，并且在动物、植物和真菌谱系分离之前出现。使用全面的系统发育分析，再加上保守的同线性和基因组组织的比较，我们表明，后生动物akirin基因的内含子-外显子结构的建立之前的bilateria和一个单一的原直向同源物复制的脊椎动物，前颚口agnathan分离，生产akirin 1和akirin 2。系统发育分析的7个脊椎动物基因家族的成员在染色体上接近akirin1和akirin2是兼容的一个共同的重复事件影响基因组邻里的akirin原直系同源物。进一步重复的akirins发生在硬骨鱼谱系，其次是谱系特定模式的paradenosloss。值得注意的是，Akirins已经被五个研究小组以不同的别名独立表征，并且对现有文献的比较揭示了不同的功能，通常在调节基因表达方面。例如，Akirin在节肢动物中被表征为subolesin，一种重要的生长因子，在果蝇中被表征为bhringi，其具有重要的生肌作用。在脊椎动物中，akirin1在小鼠中被命名为mighty，并被证明可调节肌发生，而akirin2在大鼠中被表征为FBI1，并促进癌发生，当与14 - 3 - 3蛋白结合时，作为转录抑制因子。这两种脊椎动物Akirins都是在严格的纯化选择限制下进化的，尽管似然比检验预测在旁系同源物之间发生了功能分歧。贝叶斯和最大似然检验确定了进化速率在旁系同源物之间发生显著变化的氨基酸位置。有趣的是，最高得分位置在14 - 3 - 3蛋白的保守的、经验证的结合位点内。这项工作提供了一个进化的框架，以促进未来的真核细胞Akirins的研究，并提供了深入了解他们的多方面和保守的生化功能。
Akirins are nuclear proteins that form part of an innate immune response pathway conserved in Drosophila and mice. This studies aim was to characterise the evolution of akirin gene structure and protein function in the eukaryotes. akirin genes are present throughout the metazoa and arose before the separation of animal, plant and fungi lineages. Using comprehensive phylogenetic analysis, coupled with comparisons of conserved synteny and genomic organisation, we show that the intron-exon structure of metazoan akirin genes was established prior to the bilateria and that a single proto-orthologue duplicated in the vertebrates, before the gnathostome-agnathan separation, producing akirin1 and akirin2. Phylogenetic analyses of seven vertebrate gene families with members in chromosomal proximity to both akirin1 and akirin2 were compatible with a common duplication event affecting the genomic neighbourhood of the akirin proto-orthologue. A further duplication of akirins occurred in the teleost lineage and was followed by lineage-specific patterns of paralogue loss. Remarkably, akirins have been independently characterised by five research groups under different aliases and a comparison of the available literature revealed diverse functions, generally in regulating gene expression. For example, akirin was characterised in arthropods as subolesin, an important growth factor and in Drosophila as bhringi, which has an essential myogenic role. In vertebrates, akirin1 was named mighty in mice and was shown to regulate myogenesis, whereas akirin2 was characterised as FBI1 in rats and promoted carcinogenesis, acting as a transcriptional repressor when bound to a 14-3-3 protein. Both vertebrate Akirins have evolved under comparably strict constraints of purifying selection, although a likelihood ratio test predicted that functional divergence has occurred between paralogues. Bayesian and maximum likelihood tests identified amino-acid positions where the rate of evolution had shifted significantly between paralogues. Interestingly, the highest scoring position was within a conserved, validated binding-site for 14-3-3 proteins. This work offers an evolutionary framework to facilitate future studies of eukaryotic akirins and provides insight into their multifaceted and conserved biochemical functions.
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