Finding the rules of splicing, and using them … alternatively

The last 20 years have witnessed a convergence of efforts aimed at understanding how genes produce biological complexity. In 2001, the discovery that only 25,000 genes were required to produce a human being came as a surprise because less complex organisms such as worms and flies have a similar number of genes. Recalling that the first splicing events to be documented involved the use of alternative splice sites led some to anticipate the contribution of alternative splicing to biological complexity. Although we have now reached the upper limit of close to 95%, in terms of the number of genes using alternative splicing, one exciting challenge ahead remains to describe this diversity when associated with processes such as organismal and organ development using, for example, 3D model systems. Another critical task is to continue describing the role of alternative splicing in disease and aging, and how the production of splice variants …