Origin, conservation, and loss of alternative splicing events that diversify the proteome in Saccharomycotina budding yeasts

Abstract

Many eukaryotes use RNA processing, including alternative splicing, to express multiple gene products from the same gene. The budding yeast Saccharomyces cerevisiae has been successfully used to study the mechanism of splicing and the splicing machinery, but alternative splicing in yeast is relatively rare and has not been extensively studied. Alternative splicing of SKI7/HBS1 is widely conserved, but yeast and a few other eukaryotes have replaced this one alternatively spliced gene with a pair of duplicated, unspliced genes as part of a whole genome doubling (WGD). We show that other examples of alternative splicing known to have functional consequences are widely conserved within Saccharomycotina. A common mechanism by which alternative splicing has disappeared is by replacement of an alternatively spliced gene with duplicate unspliced genes. This loss of alternative splicing does not always take place soon after duplication, but can take place after sufficient time has elapsed for speciation. Saccharomycetaceae that diverged before WGD use alternative splicing more frequently than S. cerevisiae, suggesting that WGD is a major reason for infrequent alternative splicing in yeast. We anticipate that WGDs in other lineages may have had the same effect. Having observed that two functionally distinct splice-isoforms are often replaced by duplicated genes allowed us to reverse the reasoning. We thereby identify several splice isoforms that are likely to produce two functionally distinct proteins because we find them replaced by duplicated genes in related species. We also identify some alternative splicing events that are not conserved in closely related species and unlikely to produce functionally distinct proteins.

Natural trait variation across Saccharomycotina species

“…In compiling this review, our goal has been to complement recent landmark genomic surveys of the subphylum and its variation in genome content, splicing, codon usage, and genetic parasites (Steinberg-Neifach and Lue 2015 , Dujon and Louis 2017 , Shen et al 2018 , LaBella et al 2019 , 2021 , Hurtig et al 2020 , Fredericks et al 2021 , Parker et al 2023 ). That is, since Saccharomycotina genomes have been covered so thoroughly and so recently, we focus on phenotypes instead.…”

To RNA‐binding and beyond: Emerging facets of the role of Rbfox proteins in development and disease

“…Alternative splicing is remarkably ancient and conserved, and may be traced back, albeit in a rudimentary form, to the unicellular ancestor of plants, fungi, and animals (Hurtig et al, 2020; Irimia et al, 2007). This delicate process is orchestrated by an array of factors which bind to the nascent RNA, and determine its fate.…”