Extensive compensatory cis-trans regulation in the evolution of mouse gene expression.
Extensive compensatory cis-trans regulation in the evolution of mouse gene expression.
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DOI：
10.1101/gr.142281.112
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发表时间：
2012-12
期刊：
影响因子：
7
通讯作者：
Marioni JC
中科院分区：
文献类型：
--
作者：
Goncalves A;Leigh-Brown S;Thybert D;Stefflova K;Turro E;Flicek P;Brazma A;Odom DT;Marioni JC
基因表达水平的差异被认为主要是通过物种内反式和物种间顺式调控突变来实现的。为了在哺乳动物身上验证这一假设，我们使用RNA测序来测量C57BL/6J和CAST/EIJ小鼠品系之间的基因表达差异，以及它们的F1后代中的等位基因特异性表达。我们确定了具有亲本来源特异性表达模式的基因，尽管这些基因中很少有完全等位基因沉默。这表明，在典型的小鼠体细胞组织中，印记基因的数量相对较少。在这组非印记基因中，32%的人显示出两个菌株之间表达差异的证据。其中，2%可完全归因于反式作用的变体，而43%仅可归因于作用于顺式作用的变体。反式突变导致表达差异的基因表现出明显的序列约束，而表达差异由顺式作用的变异体解释的基因则显示出更高的序列约束。其余具有不同表达模式的基因(55%)由顺式作用的变体和反式作用的变体共同调控。有趣的是，顺式和反式变体诱导的表达变化比偶然预期的更频繁地朝着相反的方向变化，这意味着稳定基因表达水平的补偿调节是普遍存在的。我们认为，受这一机制调控的基因的表达水平受到反式调控变化后出现的顺式变体的微调，这表明许多顺式变体不是自然选择的主要目标。
Gene expression levels are thought to diverge primarily via regulatory mutations in trans within species, and in cis between species. To test this hypothesis in mammals we used RNA-sequencing to measure gene expression divergence between C57BL/6J and CAST/EiJ mouse strains and allele-specific expression in their F1 progeny. We identified 535 genes with parent-of-origin specific expression patterns, although few of these showed full allelic silencing. This suggests that the number of imprinted genes in a typical mouse somatic tissue is relatively small. In the set of nonimprinted genes, 32% showed evidence of divergent expression between the two strains. Of these, 2% could be attributed purely to variants acting in trans, while 43% were attributable only to variants acting in cis. The genes with expression divergence driven by changes in trans showed significantly higher sequence constraint than genes where the divergence was explained by variants acting in cis. The remaining genes with divergent patterns of expression (55%) were regulated by a combination of variants acting in cis and variants acting in trans. Intriguingly, the changes in expression induced by the cis and trans variants were in opposite directions more frequently than expected by chance, implying that compensatory regulation to stabilize gene expression levels is widespread. We propose that expression levels of genes regulated by this mechanism are fine-tuned by cis variants that arise following regulatory changes in trans, suggesting that many cis variants are not the primary targets of natural selection.
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通过RNA-Seq对印迹基因表达的批判性评估：一种新的观点。
影响因子：
4.5
作者：
DeVeale B;van der Kooy D;Babak T
通讯作者：
Babak T
DOI：
10.1073/pnas.0805160105
发表时间：
2008-09-23
影响因子：
11.1
作者：
Lemos, Bernardo;Araripe, Luciana O.;Hartl, Daniel L.
通讯作者：
Hartl, Daniel L.
影响因子：
7
作者：
Blekhman, Ran;Marioni, John C.;Gilad, Yoav
通讯作者：
Gilad, Yoav
影响因子：
7
作者：
Vilella, Albert J.;Severin, Jessica;Birney, Ewan
通讯作者：
Birney, Ewan
影响因子：
7
作者：
Emerson, J. J.;Hsieh, Li-Ching;Li, Wen-Hsiung
通讯作者：
Li, Wen-Hsiung