Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues

被引:683
作者
Merkin, Jason [1 ]
Russell, Caitlin [1 ]
Chen, Ping [1 ,3 ,4 ]
Burge, Christopher B. [1 ,2 ]
机构
[1] MIT, Dept Biol, Cambridge, MA 02142 USA
[2] MIT, Dept Biol Engn, Cambridge, MA 02142 USA
[3] Univ Helsinki, Syst Biol Lab, Res Programs Unit, FIN-00014 Helsinki, Finland
[4] Univ Helsinki, Inst Biomed Biochem & Dev Biol, FIN-00014 Helsinki, Finland
基金
芬兰科学院;
关键词
TIGHT JUNCTIONS; TRANSCRIPTOME; CONSERVATION; EXPRESSION; ERK;
D O I
10.1126/science.1228186
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Most mammalian genes produce multiple distinct messenger RNAs through alternative splicing, but the extent of splicing conservation is not clear. To assess tissue-specific transcriptome variation across mammals, we sequenced complementary DNA from nine tissues from four mammals and one bird in biological triplicate, at unprecedented depth. We find that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is frequently lineage-specific. Thousands of previously unknown, lineage-specific, and conserved alternative exons were identified; widely conserved alternative exons had signatures of binding by MBNL, PTB, RBFOX, STAR, and TIA family splicing factors, implicating them as ancestral mammalian splicing regulators. Our data also indicate that alternative splicing often alters protein phosphorylatability, delimiting the scope of kinase signaling.
引用
收藏
页码:1593 / 1599
页数:7
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