The expression enhancing effect of introns was first recognized in the experiment using simian virus 40 constructs with or without introns, showing that their protein products were significantly diminished without their introns [15]. Subsequently, Buchman and Berg [48] showed that, in a certain condition, constructs with introns were expressed up to 400 times higher than constructs without introns, suggesting that introns can strongly enhance gene expression. In fact, some introns are designed to be included to construct expression vectors for guaranteeing a higher level of expression [49]. A large-scale analysis performed in yeast also confirmed that genes with introns tend to have a higher level of gene expression compared to genes without introns [50]. A similar observation was made in mammals, as well [51].
