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首页> 外文期刊>BMC Molecular Biology >Biased exonization of transposed elements in duplicated genes: A lesson from the TIF-IA gene
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Biased exonization of transposed elements in duplicated genes: A lesson from the TIF-IA gene

机译：重复基因中转座元素的偏性外显子化：来自TIF-IA基因的教训

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Background Gene duplication and exonization of intronic transposed elements are two mechanisms that enhance genomic diversity. We examined whether there is less selection against exonization of transposed elements in duplicated genes than in single-copy genes. Results Genome-wide analysis of exonization of transposed elements revealed a higher rate of exonization within duplicated genes relative to single-copy genes. The gene for TIFIA, an RNA polymerase I transcription initiation factor, underwent a humanoidspecific triplication, all three copies of the gene are active transcriptionally, although only one copy retains the ability to generate the TIF-IA protein. Prior to TIF-IA triplication, an Alu element was inserted into the first intron. In one of the non-protein coding copies, this Alu is exonized. We identified a single point mutation leading to exonization in one of the gene duplicates. When this mutation was introduced into the TIF-IA coding copy, exonization was activated and the level of the protein-coding mRNA was reduced substantially. A very low level of exonization was detected in normal human cells. However, this exonization was abundant in most leukemia cell lines evaluated, although the genomic sequence is unchanged in these cancerous cells compared to normal cells. Conclusions The definition of the Alu element within the TIF-IA gene as an exon is restricted to certain types of cancers; the element is not exonized in normal human cells. These results further our understanding of the delicate interplay between gene duplication and alternative splicing and of the molecular evolutionary mechanisms leading to 3 genetic innovations. This implies the existence of purifying selection against exonization in single copy genes, with duplicate genes free from such constrains.
机译：背景基因内含子转座元件的基因复制和外显子化是增强基因组多样性的两种机制。我们检查了是否有比单拷贝基因更少的针对复制基因中转座子外显子化的选择。结果转座子外显子化的全基因组分析表明，与单拷贝基因相比，重复基因中外显子发生率更高。 TIFIA的基因是一种RNA聚合酶I转录起始因子，经历了类人生物特异性的复制，该基因的所有三个副本都有转录活性，尽管只有一个副本保留了生成TIF-IA蛋白的能力。在进行TIF-IA复制之前，将Alu元件插入第一个内含子。在一种非蛋白质编码拷贝中，该Alu被外显子化。我们确定了一个单点突变，导致其中一个基因重复的外显子化。当将该突变引入TIF-IA编码拷贝中时，外显子被激活并且蛋白质编码mRNA的水平大大降低。在正常人细胞中检测到非常低的外显子水平。然而，尽管与正常细胞相比，这些癌细胞中的基因组序列没有变化，但在大多数评估的白血病细胞系中这种外显子化作用都很丰富。结论TIF-IA基因中作为外显子的Alu元素的定义仅限于某些类型的癌症。正常人细胞中该元素未被外显子化。这些结果使我们进一步了解了基因复制和选择性剪接之间的微妙相互作用，以及导致3种遗传创新的分子进化机制。这意味着在单拷贝基因中存在针对外显子化的纯化选择，而重复基因没有这种限制。

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