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Origin Recognition Complex (ORC) Evolution Is Influenced by Global Gene Duplication/Loss Patterns in Eukaryotic Genomes

机译:起源识别复合体(ORC)进化受真核基因组中全局基因复制/丢失模式的影响。

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摘要

The conservation of orthologs of most subunits of the origin recognition complex (ORC) has served to propose that the whole complex is common to all eukaryotes. However, various uncertainties have arisen concerning ORC subunit composition in a variety of lineages. Also, it is unclear whether the ancestral diversification of ORC in eukaryotes was accompanied by the neofunctionalization of some subunits, for example, role of ORC1 in centriole homeostasis. We have addressed these questions by reconstructing the distribution and evolutionary history of ORC1-5/CDC6 in a taxon-rich eukaryotic data set. First, we identified ORC subunits previously undetected in divergent lineages, which allowed us to propose a series of parsimonious scenarios for the origin of this multiprotein complex. Contrary to previous expectations, we found a global tendency in eukaryotes to increase or decrease the number of subunits as a consequence of genome duplications or streamlining, respectively. Interestingly, parasites show significantly lower number of subunits than free-living eukaryotes, especially those with the lowest genome size and gene content metrics. We also investigated the evolutionary origin of the ORC1 role in centriole homeostasis mediated by the PACT region in human cells. In particular, we tested the consequences of reducing ORC1 levels in the centriole-containing green alga . We found that the proportion of centrioles to flagella and nuclei was not dramatically affected. This, together with the PACT region not being significantly more conserved in centriole-bearing eukaryotes, supports the notion that this neofunctionalization of ORC1 would be a recent acquisition rather than an ancestral eukaryotic feature.
机译:起源识别复合体(ORC)的大多数亚基的直系同源物的保守已经提出,整个复合体是所有真核生物所共有的。但是,关于各种谱系中的ORC亚基组成已经出现了各种不确定性。同样,还不清楚真核生物中ORC的祖先多样性是否伴随着某些亚基的新功能化,例如,ORC1在中心粒体内稳态中的作用。我们已经通过在富含分类群的真核数据集中重建ORC1-5 / CDC6的分布和进化史解决了这些问题。首先,我们鉴定了以前在差异谱系中未检测到的ORC亚基,这使我们能够为该多蛋白复合物的起源提出一系列简化方案。与以前的预期相反,我们发现,由于基因组重复或精简,真核生物普遍倾向于增加或减少亚基的数量。有趣的是,与自由活动的真核生物相比,寄生虫显示出的亚基数量要少得多,尤其是那些具有最低基因组大小和基因含量指标的真核生物。我们还研究了人类细胞中PACT区域介导的中心细胞稳态中ORC1作用的进化起源。特别是,我们测试了降低含中心粒绿藻中ORC1水平的后果。我们发现,中心粒与鞭毛和细胞核的比例没有受到显着影响。这与PACT区域在带有中心粒的真核生物中并未显着保守相比,支持了ORC1的这种新功能化将是最近获得的而不是祖先的真核生物特征的观点。

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