Manuel Seefelder, Vikram Alva, Bin Huang, Tatjana Engler, Wolfgang Baumeister, Qiang Guo, Rubén Fernández-Busnadiego, Andrei N Lupas, Stefan Kochanek
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引用次数: 0
摘要
背景:亨廷顿相关蛋白40(huntingtin-associated protein 40,HAP40)与亨廷顿病(Huntington's disease,HD)中发生改变的亨廷顿蛋白(huntingtin,HTT)有大量相互作用。因此,我们分析了HAP40的进化及其与HTT的相互作用:结果:我们发现,在羊膜动物中,HAP40由单外显子基因编码,而在所有其他生物中,它由多外显子基因表达。HAP40与HTT共存于单子叶动物中,包括丝虫(如Capsaspora owczarzaki)和变形虫(Dictyostelium discoideum),但真菌中不存在这两种蛋白质。在单孔菌之外,少数物种,如自由生活的变形虫Naegleria gruberi,含有推测的HTT和HAP40直向同源物。我们的生物化学研究表明,HTT 和 HAP40 之间的相互作用延伸到了鱼类,生物信息学分析为这种相互作用的进化保护提供了证据。在目前的蛋白质数据库中,与HAP40最接近的同源物是可溶性N-乙基马来酰亚胺敏感因子附着蛋白(SNAPs)家族:我们的研究结果表明,从多外显子基因到单外显子基因的转变似乎是在两栖类和羊膜类的分化过程中通过逆位发生的,随后亲代多外显子基因丢失。此外,这两种蛋白质似乎可能起源于真核生物的根部。HAP40和HTT之间相互作用的保守性及其可能的共同进化有力地表明了这种相互作用在功能上的重要性。
The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin.
Background: The huntingtin-associated protein 40 (HAP40) abundantly interacts with huntingtin (HTT), the protein that is altered in Huntington's disease (HD). Therefore, we analysed the evolution of HAP40 and its interaction with HTT.
Results: We found that in amniotes HAP40 is encoded by a single-exon gene, whereas in all other organisms it is expressed from multi-exon genes. HAP40 co-occurs with HTT in unikonts, including filastereans such as Capsaspora owczarzaki and the amoebozoan Dictyostelium discoideum, but both proteins are absent from fungi. Outside unikonts, a few species, such as the free-living amoeboflagellate Naegleria gruberi, contain putative HTT and HAP40 orthologs. Biochemically we show that the interaction between HTT and HAP40 extends to fish, and bioinformatic analyses provide evidence for evolutionary conservation of this interaction. The closest homologue of HAP40 in current protein databases is the family of soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAPs).
Conclusion: Our results indicate that the transition from a multi-exon to a single-exon gene appears to have taken place by retroposition during the divergence of amphibians and amniotes, followed by the loss of the parental multi-exon gene. Furthermore, it appears that the two proteins probably originated at the root of eukaryotes. Conservation of the interaction between HAP40 and HTT and their likely coevolution strongly indicate functional importance of this interaction.
期刊介绍:
BMC Evolutionary Biology is an open access, peer-reviewed journal that considers articles on all aspects of molecular and non-molecular evolution of all organisms, as well as phylogenetics and palaeontology.