Minigenes were first described as the somatic assembly of DNA segments and consisted of DNA regions known to encode the protein and the flanking regions required to express the protein. The term was first used in a paper in 1977 to describe the cloning of two minigenes that were designed to express a peptide.
RNA splicing was discovered in the late 1970s through the study of adenoviruses that invade mammals and replicate inside them. Researchers identified RNA molecules that contained sequences from noncontiguous parts of the virus’s genome. This discovery led to the conclusion that regulatory mechanisms existed which affected mature RNA and the genes it expresses. Using minigenes as a splice reporting vector to explore the effects of RNA splicing regulation naturally followed and remains the major use of minigenes to date.