142 telomere-to-telomere assemblies reveal the genome structural landscape inSaccharomyces cerevisiae

Abstract

As population genomics is transitioning from single reference genomes to pangenomes, major improvements in terms of genome contiguity, phylogenetic sampling, haplotype phasing and structural variant (SV) calling are required. Here, we generated the Saccharomyces cerevisiae Reference Assembly Panel (ScRAP) comprising 142 reference-quality genomes from strains of various geographic and ecological origins that faithfully represent the genomic diversity and complexity of the species. The ca. 4,800 independent SVs we identified impact the expression of genes near the breakpoints and contribute to gene repertoire evolution through disruptions, duplications, fusions and horizontal transfers. We discovered frequent cases of complex aneuploidies, preferentially involving large chromosomes that underwent large SVs. We also characterized the evolutionary dynamics of complex genomic regions that classically remain unassembled in short read-based projects, including the 5 Ty families and the 32 individual telomeres. Overall, the ScRAP represents a crucial step towards establishing a high-quality, unified and complete S. cerevisiae pangenome.

Experimental approaches to study evolutionary cell biology using yeasts

“…While traditionally considered suboptimal for the imaging of intracellular features, super‐resolution techniques were recently developed (Chen et al, 2021; Hinterndorfer et al, 2022; Korovesi et al, 2022), and used (Dey et al, 2020) in yeast to study cellular processes at higher resolution, and new tools have been provided for the imaging of several subcellular structures (Akhuli et al, 2022; Zhu et al, 2019). A large number of telomere‐to‐telomere assemblies recently revealed the landscape of structural variants of S. cerevisiae natural isolates (O'Donnell et al, 2022). Finally, synthetic biology approaches such as The Synthetic Yeast Genome Project (S. M. Richardson et al, 2017) continue to provide novel tools to generate synthetic cellular conditions.…”

Ancient and recent origins of shared polymorphisms in yeast

“…The red blocks represent homozygous introgressions while the blue blocks are homozygous for S. cerevisiae. d-f, Neighbour-Join phylogenies (kimura 2-parameter substitution model) of the sequences spanning the genes YKR064W-YKR078W derived from de novo whole-genome assemblies 28,45,46 . The tree on panel d and f are derived from 25 kb flanking regions before and after the introgression, while the tree in panel e is the introgressed region.…”

“…alleles between the Chinese isolates. In the squared brackets the name of the strains; in the round brackets the number of sites obtained using the de novo genome assemblies 45 of BAG, AMH and CBS432 isolates depicted in the cartoon above. left) and S. cerevisiae (on the right) subgenomes of hybrid isolates (red label).…”

VRPG: an interactive visualization framework for reference-projected pangenome graph

“…To demonstrate the application of VRPG in real world examples, we set up a demonstration website (https://www.evomicslab.org/app/vrpg/) to visualize reference pangenome graphs derived from 143 yeast and 90 human genome assemblies respectively. The human reference pangenome graph is a public dataset, whereas the yeast reference pangenome graph is built based on the Saccharomyces cerevisiae reference assembly panel (ScRAP) that we recently constructed (O’Donnell et al ., 2022). Both graphs were constructed by Minigraph (Li et al ., 2020) via a standard reference pangenome graph building protocol (Supplementary Note).…”