Charalampos Rallis | Search bioRxiv

bioRxiv2016

Transient structural variations alter gene expression and quantitative traits in Schizosaccharomyces pombe.

Large structural variations (SVs) in the genome are harder to identify than smaller genetic variants but may substantially contribute to phenotypic diversity and evolution. Here we analyze the effects of SVs on gene expression, quantitative traits, and intrinsic reproductive isolation in the yeast Schizosaccharomyces pombe. We establish a high-quality curated catalog of SVs in the genomes of a worldwide library of S. pombe strains, including duplications, deletions, inversions and translocations. We show that copy number variants (CNVs) frequently segregate within closely related clonal populations, are weakly linked to single nucleotide polymorphisms (SNPs), and show other genetic signals consistent with rapid turnover. These transient CNVs produce stoichiometric effects on gene expression both within and outside the duplicated regions. CNVs make substantial contributions to quantitative traits such as cell shape, cell growth under diverse conditions, sugar utilization in winemaking, whereas rearrangements are strongly associated with reproductive isolation. Collectively, these findings have broad implications for evolution and for our understanding of quantitative traits including complex human diseases.

Genomics↗

bioRxiv2014

Skip and bin: pervasive alternative splicing triggers degradation by nuclear RNA surveillance in fission yeast

Exon-skipping is considered a principal mechanism by which eukaryotic cells expand their transcriptome and proteome repertoires, creating different slice varaiants with distinct cellular functions. Here we analyze RNA-seq data from 116 transcriptomes in fission yeast (Schizosaccharomyces pombe), covering multiple physiological conditions as well as transcriptional and RNA processing mutants. We applied brute-force algorithms to detect all possible exon-skipping events, which were ubiquitous but rare compared to canonical splicing events. Exon-skipping events increased in cells deficient for the nuclear exosome or the 5-3 exonuclease Dhp1, and also at late stages of meiotic differentiation when nuclear-exosome transcripts were down-regulated. The pervasive exon-skipping transcripts were stochastic, did not increase in specific physiological conditions, and were mostly present at below 1 copy per cell, even in the absence of nuclear RNA surveillance and late during meiosis. These exon-skipping transcripts are therefore unlikely to be functional and may reflect splicing errors that are actively removed by nuclear RNA surveillance. The average splicing error-rate was [~]0.24% in wild-type and [~]1.75% in nuclear exonuclease mutants. Using an exhaustive search algorithm, we also uncovered thousands of previously unknown splice sites, indicating pervasive splicing, yet most of these novel splicing events were rare and targeted for nuclear degradation. Analysis of human transcriptomes revealed similar, albeit much weaker trends for pervasive exon-skipping transcripts, some of which being degraded by the nuclear exosome. This study highlights widespread, but low frequency alternative splicing which is targeted by nuclear RNA surveillance.

Genomics↗