Lightning strikes twice: Intron–intein coincidence

“Multiple introns, and the prospect that these occur within several genes in the same metabolic pathway, suggest a regulatory role for splicing … ” (1). That statement was made more than a decade ago by our colleagues and ourselves in reference to the phage T4 group I introns, all three of which reside in genes involved in nucleotide metabolism. The intervening years were distinguished by a striking absence of any demonstration of a regulatory role for these introns. Furthermore, they seem not to confer any selective advantage to T4 phage, and, despite the discovery of more introns in genes of DNA metabolism, the question of “why exclusively in those genes?” has been all but forgotten. Now we are faced with a report in this issue of the Proceedings of an unrelated phage and a different type of splicing element, an intein; not only does this element coexist with a group I intron in the same gene but also the gene is one of nucleotide metabolism (2). With lightning apparently striking twice in the same place, we are again forced to confront our doubts about pure chance. What might account for the colocalization of two different types of intervening sequence in the same gene on the same metabolic pathway?