Elongated exons encoding disordered regions expedited eukaryotic evolution

Most prokaryotic proteins consist of one structural domain (SD), while a typical eukaryotic protein is comprised of multiple SDs and intrinsically disordered regions (IDRs) that by themselves do not adopt stable structures. In eukaryotes IDRs are especially prevalent in transcription factors and are involved in condensates that regulate diverse cellular functions. How eukaryotic proteins evolved to differ from prokaryotic proteins has not been fully elucidated. Here we find that the longer internal exons are, the more frequently they encode IDRs in general. Moreover, the boundaries of long internal exons tend to fall outside of structural domains. These findings are consistent with the idea that some internal exons whose boundaries were aligned outside of structural domains acquired sections encoding IDRs. Most of the internal exon segments that probably lengthened after the rat-mouse divergence encode IDRs, supporting the view. We surmise that many exons whose boundaries were not aligned to the inside of structural domains elongated to add IDRs to the encoded proteins, often conferring new functions. Some of the IDRs possibly served as spacers in acquiring structural domains through recombination. We propose that the "small bang" that lengthened exons facilitated the evolution that led to the last common ancestor of eukaryotes. ### Competing Interest Statement The authors have declared no competing interest.