Alternative Splicing Across the Tree of Life: A Comparative Study

Abstract

There is a growing understanding of how alternative splicing contributes to functional specialization and adaptation, especially in well-studied model organisms. However, its large-scale evolutionary dynamics remain poorly understood. Through a comparative analysis of alternative splicing across 1,494 species spanning the entire tree of life, this study integrates numerous lines of prior evidence to provide a unified view of alternative splicing. We propose a novel genome-scale metric designed to support cross-species comparison. Our findings indicate that alternative splicing is highly variable across lineages. While unicellular eukaryotes and prokaryotes display minimal splicing, mammals and birds exhibit the highest levels of alternative splicing. Despite sharing a conserved intron-rich genomic architecture, mammals and birds show considerable interspecies divergence in splicing activity. In contrast, plants display moderate levels of alternative splicing but exhibit high variability of genomic composition. Furthermore, a strong negative correlation is observed between alternative splicing and the proportion of coding content in genes, with the highest levels of alternative splicing observed in genomes containing approximately 50% intergenic DNA.