Domestication of self-splicing introns during eukaryogenesis: the rise of the complex spliceosomal machinery

Abstract

ᅟ: The spliceosome is a eukaryote-specific complex that is essential for the removal of introns from pre-mRNA. It consists of five small nuclear RNAs (snRNAs) and over a hundred proteins, making it one of the most complex molecular machineries. Most of this complexity has emerged during eukaryogenesis, a period that is characterised by a drastic increase in cellular and genomic complexity. Although not fully resolved, recent findings have started to shed some light on how and why the spliceosome originated. In this paper we review how the spliceosome has evolved and discuss its origin and subsequent evolution in light of different general hypotheses on the evolution of complexity. Comparative analyses have established that the catalytic core of this ribonucleoprotein (RNP) complex, as well as the spliceosomal introns, evolved from self-splicing group II introns. Most snRNAs evolved from intron fragments and the essential Prp8 protein originated from the protein that is encoded by group II introns. Proteins that functioned in other RNA processes were added to this core and extensive duplications of these proteins substantially increased the complexity of the spliceosome prior to the eukaryotic diversification. The splicing machinery became even more complex in animals and plants, yet was simplified in eukaryotes with streamlined genomes. Apparently, the spliceosome did not evolve its complexity gradually, but in rapid bursts, followed by stagnation or even simplification. We argue that although both adaptive and neutral evolution have been involved in the evolution of the spliceosome, especially the latter was responsible for the emergence of an enormously complex eukaryotic splicing machinery from simple self-splicing sequences.

Reviewers: This article was reviewed by W. Ford Doolittle, Eugene V. Koonin and Vivek Anantharaman.

Keywords: Eukaryogenesis; Evolution of complexity; Introns; Spliceosome; Splicing.

Fig. 1

Resemblance between group II introns, and spliceosomal introns and snRNAs. a Simplified secondary structure of a group II intron (IIA) with its intron-encoded protein (IEP). The largest part of domain I has been omitted. The catalytic triad and adenosine branch point are explicitly depicted. The structures are coloured based on their similarity to spliceosomal structures (b). The black RNA domains do not have homologous structures in the spliceosome. b Simplified secondary structure of a spliceosomal intron with the snRNAs and Prp8. U1 and U4 snRNA are not homologous to group II intron domains

Fig. 2

Evolution of the Sm and Lsm rings. a Tree depicting the scenario on the evolution of the spliceosomal Lsm and Sm proteins, as proposed in [90]. b Possible scenario for the evolution of the Lsm and Sm rings. A homoheptameric Lsm ring interacted with the trans-acting U6 snRNA, thereby facilitating splicing of degenerating self-splicing introns. While the Lsm ring became heteromeric upon duplication and subfunctionalisation of the Lsm protein, the trans-acting U2 and U5, which all originated from the introns, and U1 and U4 snRNAs formed RNP complexes with the Lsm ring. Upon duplication of the ring, U6 snRNA was bound by the Lsm ring, whereas the other snRNAs formed a complex with the newly formed Sm ring, followed by the addition of other proteins

Fig. 3

Evolution of the spliceosome. a Origin of the spliceosome during eukaryogenesis. The major steps resulting in the domestication of self-splicing introns in the early eukaryotes are depicted. b Subsequent evolution after eukaryogenesis resulting in the more complex or simple spliceosomes in five diverse eukaryotes. Besides the gain or loss of notable proteins the net loss or gain of introns is depicted for each lineage. The internal branches seemed to have experienced no large change of intron density [25]. The circles, except Snu114 and Brr2, represent an arbitrary number of proteins. The question marks in Giardia’s Lsm and Sm rings reflect the ambiguity about their exact composition [22, 90]