Naturally occurring antisense: Transcriptional leakage or real overlap?
Naturally occurring antisense: Transcriptional leakage or real overlap?
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DOI：
10.1101/gr.3308405
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发表时间：
2005-03-01
期刊：
影响因子：
7
通讯作者：
Sorek, R
中科院分区：
文献类型：
--
作者：
Dahary, D;Elroy-Stein, O;Sorek, R
自然发生的反义转录通过多种生物学机制与基因表达调控有关。最近的几项全基因组研究报道了数千种哺乳动物基因的潜在反义转录物的鉴定，其中许多是由选择性聚腺苷化转录物或异质转录起始位点产生的。然而，目前尚不清楚这种转录可塑性是有意的，导致转录物之间有调控的重叠，还是代表RNA转录机制的“泄漏”。为了通过所有进化方法解决这个问题，我们比较了人类，小鼠和河豚之间的基因基因组组织，有或没有反义。我们的假设是，如果两个相邻的基因重叠，并具有正反义关系，我们将期望负选择作用于它们之间的进化分离。我们发现反义基因对在整个脊椎动物进化过程中保持其基因组组织的可能性是非反义基因对的两倍，这意味着祖先基因组中存在所有重叠。此外，我们发现增加具有正反义关系的基因对之间的基因组距离是被选择的。这些发现表明，至少在一定程度上，观察到不良表达数据的反义转录物的丰度代表了真正的重叠，而不是转录泄漏。此外，我们的研究结果表明，自然反义转录在很大程度上影响了脊椎动物基因组的进化。
Naturally occurring antisense transcription is associated with the regulation of gene expression through a Variety of biological mechanisms. Several recent genome-wide studies reported the identification of potential antisense transcripts for thousands of mammalian genes, many of them resulting from alternatively polyadenylated transcripts or heterogeneous transcription start sites. However, it is not clear whether this transcriptional plasticity is intentional, leading to regulated overlap between the transcripts, or, alternatively, represents a "leakage" of the RNA transcription machinery. To address this question through all evolutionary approach, we compared the genomic organization of genes, with or without antisense, between human, mouse, and the pufferfish Fugu rubripes. Our hypothesis was that if two neighboring genes overlap and have a sense-antisense relationship, we would expect negative selection acting oil the evolutionary separation between them. We found that antisense gene pairs are twice as likely to preserve their genomic organization throughout vertebrates' evolution compared to nonantisense pairs, implying all overlap existence in the ancestral genome. In addition, we show that increasing the genomic distance between pairs of genes having a sense-antisense relationship is selected against. These findings indicate that, at least in part, the abundance of antisense transcripts observed ill expressed data represents real overlap rather than transcriptional leakage. Moreover, Our results imply that natural antisense transcription has considerably affected vertebrate genome evolution.