Evolutionary impact of limited splicing fidelity in mammalian genes

The functional significance of most alternative splicing (AS) events, especially frame-shifting ones, has been controversial. Using human–mouse comparison, we demonstrate that frame-preserving AS events adapt and get fixed more rapidly than frame-shifting AS events; selection for smaller exon size is stronger in frame-preserving exons than in frame-shifting ones. These results suggest AS events introducing mild changes are generally favored during evolution and explain the excess of shorter, frame-preserving cassette exons in present mammalian genomes.