Sense-antisense gene pairs: sequence, transcription, and structure are not conserved between human and mouse.
Sense-antisense gene pairs: sequence, transcription, and structure are not conserved between human and mouse.
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DOI：
10.3389/fgene.2013.00183
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发表时间：
2013
影响因子：
3.7
通讯作者：
Lipovich L
中科院分区：
文献类型：
--
作者：
Wood EJ;Chin-Inmanu K;Jia H;Lipovich L
以前的努力，以表征人类和小鼠基因组之间的保守性主要集中在序列比较。这些研究本质上是有限的，因为它们没有考虑基因结构差异，尽管基因组序列保守，但基因结构差异可能存在。最近的高通量转录组研究已经揭示了基因和转录本之间广泛和广泛的重叠，在基因组序列的两条链上编码。这种重叠的基因组织，产生有义-反义（SAS）基因对，能够通过已建立的机制影响调控级联反应。我们提出了一个进化的保守性评估SAS对，在三个层面上：基因组，转录组和结构。从人类SAS对的全基因组数据集，我们首先确定了小鼠基因组中的orthopathy位点，然后评估了它们在小鼠中的转录，最后比较了两个物种中表达的SAS对的基因组结构。我们发现，大约一半的人SAS基因座在小鼠基因组中具有单一的orthopathic位置，然而，只有一半的orthopathic位置在小鼠中具有SAS转录活性。这表明高的人-小鼠基因保守性忽略了SAS对发生率和表达的广泛差异。我们比较了在orthopathy SAS位点的基因结构，发现人类和orthopathy小鼠SAS对成员之间的基因结构经常存在差异。我们对人类SAS对小鼠表达保守性以及结构的分类指出了小鼠模型的局限性。基因结构的差异，包括在SAS基因座，可能占灵长类动物和啮齿类动物之间的一些表型差异。非保守SAS对中的基因可能有助于进化谱系特异性调控结果。
Previous efforts to characterize conservation between the human and mouse genomes focused largely on sequence comparisons. These studies are inherently limited because they don't account for gene structure differences, which may exist despite genomic sequence conservation. Recent high-throughput transcriptome studies have revealed widespread and extensive overlaps between genes, and transcripts, encoded on both strands of the genomic sequence. This overlapping gene organization, which produces sense-antisense (SAS) gene pairs, is capable of effecting regulatory cascades through established mechanisms. We present an evolutionary conservation assessment of SAS pairs, on three levels: genomic, transcriptomic, and structural. From a genome-wide dataset of human SAS pairs, we first identified orthologous loci in the mouse genome, then assessed their transcription in the mouse, and finally compared the genomic structures of SAS pairs expressed in both species. We found that approximately half of human SAS loci have single orthologous locations in the mouse genome; however, only half of those orthologous locations have SAS transcriptional activity in the mouse. This suggests that high human-mouse gene conservation overlooks widespread distinctions in SAS pair incidence and expression. We compared gene structures at orthologous SAS loci, finding frequent differences in gene structure between human and orthologous mouse SAS pair members. Our categorization of human SAS pairs with respect to mouse conservation of expression as well as structure points to limitations of mouse models. Gene structure differences, including at SAS loci, may account for some of the phenotypic distinctions between primates and rodents. Genes in non-conserved SAS pairs may contribute to evolutionary lineage-specific regulatory outcomes.