Complex genomic rearrangements lead to novel primate gene function
Complex genomic rearrangements lead to novel primate gene function
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DOI：
10.1101/gr.3266405
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发表时间：
2005-03-01
期刊：
影响因子：
7
通讯作者：
Bork, P
中科院分区：
文献类型：
--
作者：
Ciccarelli, FD;von Mering, C;Bork, P
在大范围物种中保持单拷贝状态的直向同源基因可能表明对基因复制的选择。如果是这样的话，那么存活下来的基因的复制品可能已经通过其功能的快速和相当大的变化而逃脱了剂量控制。为了验证这一假设，并制定一个新的基因功能的识别策略，我们分析了22灵长类动物特异性染色体内重复的基因与所有其他完全测序后生动物的单拷贝直系同源物。当将这组基因与不受单拷贝状态约束的基因进行比较时，我们观察到前者更倾向于修改其基因结构，通常是通过复杂的基因组重排。对影响人类2号染色体10%的最引人注目的重复的分析，使得能够详细地重建导致新基因家族出现的事件。该家族的八个成员起源于高度保守的核孔蛋白RanBP 2，通过几种遗传重排，如片段复制、倒位、易位、外显子丢失和结构域增加。我们已经通过实验证实，至少有一个新形成的蛋白质具有不同于RanBP2的细胞定位，我们表明，积极的选择在进化过程中的特定领域的作用。
Orthologous genes that maintain a single-copy status in a broad range of species may indicate a selection against gene duplication. If this is the case, then duplicates of such genes that do survive may have escaped the dosage control by rapid and sizable changes in their function. To test this hypothesis and to develop a strategy for the identification of novel gene functions, we have analyzed 22 primate-specific intrachromosomal duplications of genes with a single-copy ortholog in all other completely sequenced metazoans. When comparing this set to genes not exposed to the single-copy status constraint, we observed a higher tendency of the former to modify their gene structure, often through complex genomic rearrangements. The analysis of the most dramatic of these duplications, affecting similar to10% of human Chromosome 2, enabled a detailed reconstruction of the events leading to the appearance of a novel gene family. The eight members of this family originated from the highly conserved nucleoporin RanBP2 by several genetic rearrangements such as segmental duplications, inversions, translocations, exon loss, and domain accretion. We have experimentally verified that at least one of the newly formed proteins has a cellular localization different from RanBP2's, and we show that positive selection did act on specific domains during evolution.