The splice of life: how alternative splicing shapes regulatory and phenotypic evolution

Alternative splicing (AS) is a key mechanism for generating regulatory and phenotypic diversity in multicellular eukaryotes. Large-scale comparative transcriptomic studies have revealed that AS leads to lineage-specific and tissue-specific transcriptomic and proteomic changes, underscoring its contribution to the evolution of gene products and functions. In this review, we highlight the patterns and mechanisms of AS evolution across species, exploring how technological advancements are transforming our understanding of splicing evolution. Furthermore, we discuss mechanistic and functional insights from recent studies, including groundbreaking discoveries on how AS has shaped phenotypic evolution in mammals.