Evolutionary dynamics of gene and isoform regulation in mammalian tissues

Most mammalian genes produce multiple distinct mRNAs through alternative splicing, but the extent of splicing conservation is not clear. To assess tissue-specific transcriptome variation across mammals, we sequenced cDNA from 9 tissues from 4 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 novel, 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 indicates that alternative splicing is often used to alter protein phosphorylatability, delimiting the scope of kinase signaling. Tissue transcriptomes from 9 tissues from 5 species, 3 individuals per species, were sequenced and compared (two samples for mouse_heart). Curation note: E-GEOD-41637 (9 tissues, 5 organisms) has been split into five artefactual ArrayExpress experiments, one experiment per species for inclusion in Expression Atlas. Each artefactual experiment omits the processed data files (which are still available via the original E-GEOD-41637 records). Chicken: E-MTAB-2797; Cow: E-MTAB-2798; Rhesus monkey: E-MTAB-2799; Rat: E-MTAB-2800; Mouse: E-MTAB-2801