Multi-species microarrays reveal the effect of sequence divergence on gene expression profiles

Multi-species microarrays reveal the effect of sequence divergence on gene expression profiles
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DOI:
10.1101/gr.3335705
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发表时间:
2005-05-01
期刊:
影响因子:
7
通讯作者:
White, KP
White, KP
中科院分区:
生物学1区
文献类型:
--
作者:
Gilad, Y;Rifkin, SA;White, KP

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基因表达水平的种间比较将增加我们对转录机制进化的理解,并有助于识别自然选择的靶标。这种方法对猿类有特殊的希望,因为许多人类特异性适应被认为是由于基因表达而不是不良编码顺序引起的。但是,迄今为止,所有直接比较种间基因表达的研究均在单物种阵列上进行,因此由于序列不匹配而与潜在的表达差异,不可能区分差异杂交。为了评估该潜在问题的严重程度,我们使用人,黑猩猩,猩猩和若斯氏菌的探针构建了一个新的多气候cDNA阵列。我们发现序列发散油杂交信号的效果很大,即使在最接近的物种,人类和黑猩猩中也是如此。通过将单物种阵列分析与多种阵列的结果进行比较,我们研究了差异基因表达的估计值如何受序列差异的影响。我们的结果表明,在直接种间比较中幼稚地使用单物种阵列可以产生虚假的结果。
Interspecies comparisons of gene expression levels will increase Our understanding of the evolution of transcriptional mechanism and help to identify targets of natural selection. This approach holds particular promise for apes, as many human-specific adaptations are thought to result from differences in gene expression rather than ill coding sequence. To date, however, all Studies directly comparing interspecies gene expression have been performed on single-species arrays, so that it has been impossible to distinguish differential hybridization due to sequence mismatches from underlying expression differences. To evaluate the severity of this potential problem, we constructed a new multiprimate cDNA array using probes from human, chimpanzee, orangutan, and rheSLIS. We find a large effect of sequence divergence oil hybridization signal, even in the closest pair of species, human and chimpanzee. By comparing single-species array analyses with results from multispecies arrays, we examine how estimates of differential gene expression are affected by sequence divergence. Our results indicate that naive use of single-species arrays in direct interspecies comparisons can yield Spurious results.