The study investigates the evolutionary dynamics of gene and isoform regulation in mammalian tissues by analyzing transcriptome sequencing data from nine tissues across four mammals and one bird. The researchers found that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is often lineage-specific. They identified thousands of novel, lineage-specific, and conserved alternative exons, which were associated with binding by splicing factors such as MBNL, PTB, RBFOX, STAR, and TIA. These findings suggest that alternative splicing can alter protein phosphorylatability, influencing kinase signaling. The study also revealed that tissue-specific alternative splicing is often used to control the scope of signaling networks, connecting specific kinases to specific targets in a cell- or tissue-restricted manner.The study investigates the evolutionary dynamics of gene and isoform regulation in mammalian tissues by analyzing transcriptome sequencing data from nine tissues across four mammals and one bird. The researchers found that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is often lineage-specific. They identified thousands of novel, lineage-specific, and conserved alternative exons, which were associated with binding by splicing factors such as MBNL, PTB, RBFOX, STAR, and TIA. These findings suggest that alternative splicing can alter protein phosphorylatability, influencing kinase signaling. The study also revealed that tissue-specific alternative splicing is often used to control the scope of signaling networks, connecting specific kinases to specific targets in a cell- or tissue-restricted manner.