Widespread and subtle: alternative splicing at short-distance tandem sites

Alternative splicing at donor or acceptor sites located just a few nucleotides apart is widespread in many species. It results in subtle changes in the transcripts and often in the encoded proteins. Several of these tandem splice events contribute to the repertoire of functionally different proteins, whereas many are neutral or deleterious. Remarkably, some of the functional events are differentially spliced in tissues or developmental stages, whereas others exhibit constant splicing ratios, indicating that function is not always associated with differential splicing. Stochastic splice site selection seems to play a major role in these processes. Here, we review recent progress in understanding functional and evolutionary aspects as well as the mechanism of splicing at short-distance tandem sites.