An Overview of the Introns-First Theory

David Penny, Marc P. Hoeppner, Anthony M. Poole, Daniel C. Jeffares

We review the introns-first hypothesis a decade after it was first proposed. It is that exons emerged from non-coding regions interspersed between RNA genes in an early RNA world, and is a subcomponent of a more general 'RNA-continuity' hypothesis. The latter is that some RNA-based systems, especially in RNA processing, are 'relics' that can be traced back either to the RNA world that preceded both DNA and encoded protein synthesis or to the later ribonucleoprotein (RNP) world (before DNA took over the main coding role). RNA-continuity is based on independent evidence-in particular, the relative inefficiency of RNA catalysis compared with protein catalysis-and leads to a wide range of predictions, ranging from the origin of the ribosome, the spliceosome, small nucleolar RNAs, RNases P and MRP, and mRNA, and it is consistent with the wide involvement of RNA-processing and regulation of RNA in modern eukaryotes. While there may still be cause to withhold judgement on intron origins, there is strong evidence against introns being uncommon in the last eukaryotic common ancestor (LECA), and expanding only within extant eukaryotic groups-the 'very-late' intron invasion model. Similarly, it is clear that there are selective forces on numbers and positions of introns; their existence may not always be neutral. There is still a range of viable alternatives, including introns first, early, and 'latish' (i.e. well established in LECA), and regardless of which is ultimately correct, it pays to separate out various questions and to focus on testing the predictions of sub-theories.