CYNTENATOR: progressive gene order alignment of 17 vertebrate genomes.
CYNTENATOR: progressive gene order alignment of 17 vertebrate genomes.
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DOI：
10.1371/journal.pone.0008861
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发表时间：
2010-01-28
期刊：
影响因子：
3.7
通讯作者：
Dieterich C
中科院分区：
文献类型：
--
作者：
Rödelsperger C;Dieterich C
高等真核生物的全基因组基因顺序进化最初被认为是一个随机过程。基因顺序保守或保守同线性被视为共同血统的特征，并不意味着功能限制的存在。这种观点必须根据数十种脊椎动物基因组测序的结果进行修正。很明显，在漫长的进化过程中，存在其他因素限制某些基因组区域的基因顺序。在这些区域之外，基因组在基因内容和顺序方面的分歧更快。我们开发了 CYNTENATOR，一种渐进式基因顺序比对软件，用于识别大量不同物种中保守同线性的基因组区域。 CYNTENATOR 不依赖于核苷酸水平比对和先验同源性分配。我们的软件利用底层系统发育实现了改进的评分功能。在这份手稿中，我们报告了我们的渐进式基因顺序比对方法，并与以前的软件进行了比较，并对 17 个脊椎动物基因组进行了基因顺序保护的分析。 CYNTENATOR 的运行时间复杂度为 ，空间复杂度为 ，其中基因组中的基因编号为 。 CYNTENATOR 在模拟成对基因顺序比较方面的表现与最先进的软件一样好，但它是唯一在实践中可用于比对数十个脊椎动物大小的基因顺序的算法。 17 个脊椎动物基因组的基因顺序的谱系特异性表征揭示了维持保守同线性的机制，例如增强子和双向启动子的共调节。在灵长类基因组比较中，保守同线性块之外的基因显示出参与对外部刺激、免疫和嗅觉反应等刺激的反应的基因的富集。我们甚至看到靠近系统发育根的祖先节点断点区域的基因本体术语显着丰富。此外，我们对转座元件的分析揭示了哺乳动物断点区域中 LINE-1 元件的显着积累。总之，CYNTENATOR 是一种灵活且可扩展的工具，用于识别多个物种在长进化距离上的保守基因顺序。
Whole genome gene order evolution in higher eukaryotes was initially considered as a random process. Gene order conservation or conserved synteny was seen as a feature of common descent and did not imply the existence of functional constraints. This view had to be revised in the light of results from sequencing dozens of vertebrate genomes. It became apparent that other factors exist that constrain gene order in some genomic regions over long evolutionary time periods. Outside of these regions, genomes diverge more rapidly in terms of gene content and order. We have developed CYNTENATOR, a progressive gene order alignment software, to identify genomic regions of conserved synteny over a large set of diverging species. CYNTENATOR does not depend on nucleotide-level alignments and a priori homology assignment. Our software implements an improved scoring function that utilizes the underlying phylogeny. In this manuscript, we report on our progressive gene order alignment approach, a and give a comparison to previous software and an analysis of 17 vertebrate genomes for conservation in gene order. CYNTENATOR has a runtime complexity of and a space complexity of with being the gene number in a genome. CYNTENATOR performs as good as state-of-the-art software on simulated pairwise gene order comparisons, but is the only algorithm that works in practice for aligning dozens of vertebrate-sized gene orders. Lineage-specific characterization of gene order across 17 vertebrate genomes revealed mechanisms for maintaining conserved synteny such as enhancers and coregulation by bidirectional promoters. Genes outside conserved synteny blocks show enrichments for genes involved in responses to external stimuli, stimuli such as immunity and olfactory response in primate genome comparisons. We even see significant gene ontology term enrichments for breakpoint regions of ancestral nodes close to the root of the phylogeny. Additionally, our analysis of transposable elements has revealed a significant accumulation of LINE-1 elements in mammalian breakpoint regions. In summary, CYNTENATOR is a flexible and scalable tool for the identification of conserved gene orders across multiple species over long evolutionary distances.
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