Merkin Jason J, Chen Ping, Alexis Maria S, Hautaniemi Sampsa K, Burge Christopher B
Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Research Programs Unit, Genome-Scale Biology and Institute of Biomedicine, University of Helsinki, 00014 Helsinki, Finland.
Cell Rep. 2015 Mar 31;10(12):1992-2005. doi: 10.1016/j.celrep.2015.02.058. Epub 2015 Mar 19.
Mammalian genes are composed of exons, but the evolutionary origins and functions of new internal exons are poorly understood. Here, we analyzed patterns of exon gain using deep cDNA sequencing data from five mammals and one bird, identifying thousands of species- and lineage-specific exons. Most new exons derived from unique rather than repetitive intronic sequence. Unlike exons conserved across mammals, species-specific internal exons were mostly located in 5' UTRs and alternatively spliced. They were associated with upstream intronic deletions, increased nucleosome occupancy, and RNA polymerase II pausing. Genes containing new internal exons had increased gene expression, but only in tissues in which the exon was included. Increased expression correlated with the level of exon inclusion, promoter proximity, and signatures of cotranscriptional splicing. Altogether, these findings suggest that increased splicing at the 5' ends of genes enhances expression and that changes in 5' end splicing alter gene expression between tissues and between species.
哺乳动物基因由外显子组成，但新的内部外显子的进化起源和功能却知之甚少。在这里，我们利用来自五种哺乳动物和一种鸟类的深度cDNA测序数据，分析了外显子获得模式，鉴定出数千个物种特异性和谱系特异性外显子。大多数新外显子源自独特的而非重复的内含子序列。与在哺乳动物中保守的外显子不同，物种特异性内部外显子大多位于5'非翻译区（UTR）且存在可变剪接。它们与上游内含子缺失、核小体占据增加以及RNA聚合酶II暂停有关。含有新内部外显子的基因表达增加，但仅在包含该外显子的组织中如此。表达增加与外显子包含水平、启动子接近程度以及共转录剪接特征相关。总之，这些发现表明基因5'端剪接增加会增强表达，并且5'端剪接的变化会改变组织间和物种间的基因表达。
