Phylogenetic and structural analysis of centromeric DNA and kinetochore proteins.
Phylogenetic and structural analysis of centromeric DNA and kinetochore proteins.
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DOI：
10.1186/gb-2006-7-3-r23
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发表时间：
2006
期刊：
影响因子：
12.3
通讯作者：
Sorger PK
中科院分区：
文献类型：
--
作者：
Meraldi P;McAinsh AD;Rheinbay E;Sorger PK
对着丝粒DNA和动粒蛋白的分析表明，从酵母到人类，动粒的关键结构特征一直很好地保守。动粒是大型多蛋白质结构，组装在着丝粒DNA（CEN DNA）上，并介导染色体与微管的结合。酿酒酵母动粒由125个CEN DNA碱基对和70种或更多蛋白质组分组成，是人们最了解的动粒之一。相比之下，大多数真菌、植物和动物细胞在更长、更复杂的CEN上组装动粒，这就提出了一个问题：尽管CEN序列存在相当大的差异，但动粒结构是否在进化过程中得到了保护。使用计算方法，从序列相似性搜索到隐马尔可夫模型为基础的建模，我们表明，生物体的CEN类似于那些在S。酿酒酵母（点CEN）是非常密切相关的，都含有一组11个动粒蛋白质没有发现在生物体与复杂的CEN。相反，具有复杂CEN（区域CEN）的生物体含有似乎不存在于点CEN生物体中的蛋白质。然而，至少四分之三的已知动粒蛋白存在于所有真菌中，无论CEN组织如何。这些蛋白质中至少有六种具有先前未鉴定的人类直系同源物。当比较真菌和后生动物时，几乎所有的都有围绕Spc105和三个保守的多蛋白质接头复合物（MIND，COMA和NDC 80复合物）构建的动粒。我们的数据表明，动粒的关键结构特征已经很好地保存从酵母到人。令人惊讶的是，系统发育分析表明，人类动粒蛋白序列相似，他们的酵母同行假定果蝇或秀丽隐杆线虫直系同源。这一发现与动粒蛋白相对于其他复杂细胞结构的组分进化非常迅速的证据相一致。
Analysis of centromeric DNA and kinetochore proteins suggests that critical structural features of kinetochores have been well conserved from yeast to man. Kinetochores are large multi-protein structures that assemble on centromeric DNA (CEN DNA) and mediate the binding of chromosomes to microtubules. Comprising 125 base-pairs of CEN DNA and 70 or more protein components, Saccharomyces cerevisiae kinetochores are among the best understood. In contrast, most fungal, plant and animal cells assemble kinetochores on CENs that are longer and more complex, raising the question of whether kinetochore architecture has been conserved through evolution, despite considerable divergence in CEN sequence. Using computational approaches, ranging from sequence similarity searches to hidden Markov model-based modeling, we show that organisms with CENs resembling those in S. cerevisiae (point CENs) are very closely related and that all contain a set of 11 kinetochore proteins not found in organisms with complex CENs. Conversely, organisms with complex CENs (regional CENs) contain proteins seemingly absent from point-CEN organisms. However, at least three quarters of known kinetochore proteins are present in all fungi regardless of CEN organization. At least six of these proteins have previously unidentified human orthologs. When fungi and metazoa are compared, almost all have kinetochores constructed around Spc105 and three conserved multi-protein linker complexes (MIND, COMA, and the NDC80 complex). Our data suggest that critical structural features of kinetochores have been well conserved from yeast to man. Surprisingly, phylogenetic analysis reveals that human kinetochore proteins are as similar in sequence to their yeast counterparts as to presumptive Drosophila melanogaster or Caenorhabditis elegans orthologs. This finding is consistent with evidence that kinetochore proteins have evolved very rapidly relative to components of other complex cellular structures.