Abstract
Introns are a prevalent feature of eukaryotic genomes, yet their origins and contributions to genome function and evolution remain mysterious. In budding yeast, repression of the highly transcribed intron-containing ribosomal protein genes (RPGs) globally increases splicing of non-RPG transcripts through reduced competition for the spliceosome. We show that under these “hungry spliceosome” conditions, splicing occurs at more than 150 previously unannotated locations we call protointrons that do not overlap known introns. Protointrons use a less constrained set of splice sites and branchpoints than standard introns, including in one case AT-AC in place of GT-AG. Protointrons are not conserved in all closely related species, suggesting that most are not under positive selection and are fated to disappear. Some are found in non-coding RNAs (e. g. CUTs and SUTs), where they may contribute to the creation of new genes. Others are found across boundaries between noncoding and coding sequences, or within coding sequences, where they offer pathways to the creation of new protein variants, or new regulatory controls for existing genes. We define protointrons as (1) nonconserved intron-like sequences that are (2) infrequently spliced, and importantly (3) are not currently understood to contribute to gene expression or regulation in the way that standard introns function. A very few protointrons in S. cerevisiae challenge this classification by their increased splicing frequency and potential function, consistent with the proposed evolutionary process of “intronization”, whereby new standard introns are created. This snapshot of intron evolution highlights the important role of the spliceosome in the expansion of transcribed genomic sequence space, providing a pathway for the rare events that may lead to the birth of new eukaryotic genes and the refinement of existing gene function.
Highlights
Eukaryotic genes are often split by intervening sequences called introns that are removed during and after transcription by the spliceosome and associated splicing proteins
Deeper RNA sequencing of a nonsense-mediated decay deficient strain confirms a class of rare splicing events in Saccharomyces cerevisiae
In addition to the standard introns, we observe more than 600 splicing events that result from use of alternative 3’ or 5’ splice sites overlapping the standard introns
Summary
Eukaryotic genes are often split by intervening sequences called introns that are removed during and after transcription by the spliceosome and associated splicing proteins. One allows diversification of the structure and function of the RNA and protein products of a gene by producing multiple distinct mRNAs through alternative splicing [2]. The complex gene architecture of multicellular organisms, as contrasted with the simpler gene architecture in many single-celled eukaryotes, has prompted widespread speculation that alternative splicing is responsible for emergent complexity in metazoans. It contributes in complex and critical ways to gene function and regulation in extant eukaryotes, how splicing came to reside so pervasively in the eukaryotic lineage remains to be explained [4,5,6]
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