Exon Shuffling - History

History

Exon shuffling was first introduced in 1978 when Walter Gilbert discovered that the existence of introns could play a major role in the evolution of proteins. It was noted that recombination within introns could help assort exons independently and that repetitive segments in the middle of introns could create hotspots for recombination to shuffle the exonic sequences. However, the presence of these introns in eukaryotes and absence in prokaryotes created a debate about the time in which these introns appeared. Two theories arose: the “introns early” theory and the “introns late” theory. Supporters of the “introns early theory” believed that introns and RNA splicing were the relics of the RNA world and therefore both prokaryotes and eukaryotes had introns in the beginning. However, prokaryotes eliminated their introns in order to obtain a higher efficiency, while eukaryotes retained the introns and the genetic plasticity of the ancestors. On the other hand supporters of the “introns late” theory believe that prokaryotic genes resemble the ancestral genes and introns were inserted later in the genes of eukaryotes. What is clear now is that the eukaryotic exon-intron structure is not static, introns are continually inserted and removed from genes and the evolution of introns evolves parallel to exon shuffling. In order for exon shuffling to start to play a major role in protein evolution the appearance of spliceosomal introns had to take place. This was due to the fact that the self-splicing introns of the RNA world were unsuitable for exon-shuffling by intronic recombination. These introns had an essential function and therefore could not be recombined. In addition it has been proven that spliceosomal introns evolved fairly recently and are restricted in their evolutionary distribution. Therefore exon shuffling became a major role in the construction of younger proteins. Moreover, to define more precisely the time when exon shuffling became significant in eukaryotes, the evolutionary distribution of modular proteins that evolved through this mechanism were examined in different organisms (i.e., Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana, etc.) These studies suggested that there was an inverse relationship between the genome compactness and the proportion of intronic and repetitive sequences. As well as the fact that exon shuffling became significant after metazoan radiation.