Sex-specific and lineage-specific alternative splicing in primates
Sex-specific and lineage-specific alternative splicing in primates
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DOI：
10.1101/gr.099226.109
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发表时间：
2010-02-01
期刊：
影响因子：
7
通讯作者：
Gilad, Yoav
中科院分区：
文献类型：
--
作者：
Blekhman, Ran;Marioni, John C.;Gilad, Yoav
基因调控的比较研究表明，自然选择在塑造物种内和物种间的基因表达模式方面起着重要作用。然而，这些研究大多使用微阵列探针来估计基因表达水平，而这些探针仅设计用于与每个基因的一小部分进行杂交。在此，我们利用最近开发的RNA测序技术，避开了这一局限，比以往更详细地评估了基因调控过程中的种内和种间变异。具体而言，我们使用RNA - seq研究人类、黑猩猩和恒河猴的转录水平，使用来自每个物种的三只雄性和三只雌性的肝脏RNA样本。我们的方法使我们能够识别出大量在灵长类动物中其表达水平可能在自然选择下进化的基因。其中包括在这三个物种中具有保守的性别二态性表达模式的一部分基因，我们发现这些基因在脂质代谢相关基因中富集。我们的数据还表明，虽然可变剪接在物种内和物种间受到严格调控，但不同剪接形式表达的性别特异性和谱系特异性变化也很频繁。有趣的是，在那些外显子使用发生变化仅出现在人类谱系的基因中，我们发现参与解剖结构和形态发生的基因富集，这增加了一种可能性，即可变剪接调控的差异是人类进化的一种重要力量。
Comparative studies of gene regulation suggest an important role for natural selection in shaping gene expression patterns within and between species. Most of these studies, however, estimated gene expression levels using microarray probes designed to hybridize to only a small proportion of each gene. Here, we used recently developed RNA sequencing protocols, which sidestep this limitation, to assess intra- and interspecies variation in gene regulatory processes in considerably more detail than was previously possible. Specifically, we used RNA-seq to study transcript levels in humans, chimpanzees, and rhesus macaques, using liver RNA samples from three males and three females from each species. Our approach allowed us to identify a large number of genes whose expression levels likely evolve under natural selection in primates. These include a subset of genes with conserved sexually dimorphic expression patterns across the three species, which we found to be enriched for genes involved in lipid metabolism. Our data also suggest that while alternative splicing is tightly regulated within and between species, sex-specific and lineage-specific changes in the expression of different splice forms are also frequent. Intriguingly, among genes in which a change in exon usage occurred exclusively in the human lineage, we found an enrichment of genes involved in anatomical structure and morphogenesis, raising the possibility that differences in the regulation of alternative splicing have been an important force in human evolution.