title: Evolutionary dynamics of gene and isoform regulation in Mammalian tissues.
abstract: 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.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Merkin
authors.forename: Caitlin
authors.initials: C
authors.lastname: Russell
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Burge
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D005075:Biological Evolution; D002417:Cattle; D002645:Chickens; D017124:Conserved Sequence; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism; D019143:Evolution, Molecular; D005091:Exons; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007438:Introns; D008253:Macaca mulatta; D008297:Male; D008322:Mammals / Q000235:genetics*; D051379:Mice; D008957:Models, Genetic; D010766:Phosphorylation; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017422:Sequence Analysis, DNA; D059467:Transcriptome
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C479922:Mbnl1 protein, mouse; D020033:Protein Isoforms; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins; D011494:Protein Kinases