Transient structural variations have strong effects on quantitative traits and reproductive isolation in fission yeast

Abstract

Large structural variations (SVs) within genomes are more challenging to identify than smaller genetic variants but may substantially contribute to phenotypic diversity and evolution. We analyse the effects of SVs on gene expression, quantitative traits and intrinsic reproductive isolation in the yeast Schizosaccharomyces pombe. We establish a high-quality curated catalogue 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) show a variety of 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, most notably intracellular amino acid concentrations, growth under stress and 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.

Veni, vidi, vici: the success of wtf meiotic drivers in fission yeast

“…Despite the similarity, it is common to observe reproductive isolation between different S. pombe isolates. Hybridization between S. pombe strains often yields <50% viable offspring (Avelar, Perfeito, Gordo, & Ferreira, ; Hu et al, ; Jeffares et al, ; Zanders et al, ). This is in sharp contrast with Saccharomyces sensu stricto yeast where crosses for genotypes with >99% similarity generally have high fertility (Hou, Friedrich, de Montigny, & Schacherer, ).…”

“…The other verified cause of S. pombe hybrid infertility is chromosome rearrangements (Avelar et al, 2013;Hu et al, 2015;Jeffares et al, 2017;Zanders et al, 2014). Karyotype changes are common in S. pombe: changes dramatic enough to be detected on pulse-field gels were present in~20% of natural isolates (Brown et al, 2011;Jeffares et al, 2017). The high level of karyotype diversity in the S. pombe population is remarkable because of the high reproductive costs of chromosome rearrangements when heterozygous.…”

“…There are several, non-mutually exclusive explanations for this paradox. One is that rearrangements can give rise to beneficial phenotypes and be maintained by selection (Avelar et al, 2013;Jeffares et al, 2017). Another explanation is that S. pombe could infrequently outcross, minimizing the fertility costs of rearrangements.…”

DangerTrack: A scoring system to detect difficult-to-assess regions

“…These Variant Call Format (VCF) datasets were converted into BED files using SURVIVOR ( Jeffares et al , 2017) (available from https://github.com/fritzsedlazeck/SURVIVOR). Each SV was represented by two entries in the BED file, listing the breakpoints of each reported SV.…”

Nanopore sequencing of complex genomic rearrangements in yeast reveals mechanisms of repeat-mediated double-strand break repair

“…More recently, whole-genome and exome sequencing has been used to detect structural variation in model systems, human populations, cancer, and other settings (Kidd et al 2008;Stephens et al 2009; The 1000 Genomes Project Consortium et al 2010;Macintyre et al 2016;Jeffares et al 2017). Copy number changes are represented by changes in read depth, and the sequences themselves can reveal junctions.…”