Exonization of transposed elements: A challenge and opportunity for evolution

Protein-coding genes are composed of exons and introns flanked by untranslated regions. Before the mRNA of a gene can be translated into protein, the splicing machinery removes all the intronic regions and joins the protein-coding exons together. Exonization is a process, whereby genes acquire new exons from non-protein-coding, primarily intronic, DNA sequences. Genomic insertions or point mutations within DNA sequences often generate alternative splice sites, causing the splicing system to include new sequences as exons or to elongate existing exons. Because the alternative splice sites are not as efficient as the originals the new variants usually constitute a minor fraction of mature mRNAs. While the prevailing original splice variant maintains functionality, the additional sequence, free from selection pressure, evolves a new function or eventually vanishes. If the new splice variant is advantageous, selection might operate to optimize the new splice sites and consequently increase the proportion of the alternative splice variant. In some instances, the original splice variant is completely replaced by constitutive splicing of the new form. Because of the fortuitous presence of internal splice site-like structures within their sequences, portions of transposed elements frequently serve as modules of exonization. Their recruitment requires a long and versatile optimization process involving multiple changes over a time span of millions, even hundreds of millions, of years. Comparisons of corresponding genes and mRNAs in phylogenetically related species enables one to chronologically reconstruct such changes, from ancient ancestors to living species, in a stepwise manner. We will review this process using three different exemplary cases: (1) the evolution of a constitutively spliced mammalian-wide repeat (MIR), (2) the evolution of an alternative exon 1 from an alternative 5'-extended primary transcript containing an Alu element, and (3) a rare case of the stepwise exoniztion of an Alu element-derived sequence mediated by A-to-I RNA editing. (C) 2011 Elsevier Masson SAS. All rights reserved.