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. Additionally there is strong evidence 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 such as Escherichia coli, Saccharomyces cerevisiae, and Arabidopsis thaliana. These studies suggested that there was an inverse relationship between the genome compactness and the proportion of intronic and repetitive sequences, and that exon shuffling became significant after metazoan radiation. Mechanisms Crossover during sexual recombination of parental genomes Evolution of eukaryotes is mediated by sexual recombination of parental genomes and since introns are longer than exons most of the crossovers occur in noncoding regions. In these introns there are large numbers of transposable elements and repeated sequences which promote recombination of nonhomologous genes. In addition it has also been shown that mosaic proteins are composed of mobile domains which have spread to different genes during evolution and which are capable of folding themselves. There is a mechanism for the formation and shuffling of said domains, this is the modularization hypothesis. This mechanism is divided into three stages. The first stage is the insertion of introns at positions that correspond to the boundaries of a protein domain. The second stage is when the "protomodule" undergoes tandem duplications by recombination within the inserted introns. The third stage is when one or more protomodules are transferred to a different nonhomologous gene by intronic recombination. All states of modularization have been observed in different domains such as those of hemostatic proteins. Transposon mediated Long interspersed element (LINE)-1 A potential mechanism for exon shuffling is the long interspersed element (LINE) -1 mediated 3' transduction. However it is important first to understand what LINEs are. LINEs are a group of genetic elements that are found in abundant quantities in eukaryotic genomes. LINE-1 is the most common LINE found in humans. It is transcribed by RNA polymerase II to give an mRNA that codes for two proteins: ORF1 and ORF2, which are necessary for transposition. Upon transposition, L1 associates with 3' flanking DNA and carries the