The Awesome Power of Yeast Evolutionary Genetics: New Genome Sequences and Strain Resources for the Saccharomyces sensu stricto Genus

Abstract

High-quality, well-annotated genome sequences and standardized laboratory strains fuel experimental and evolutionary research. We present improved genome sequences of three species of Saccharomyces sensu stricto yeasts: S. bayanus var. uvarum (CBS 7001), S. kudriavzevii (IFO 1802(T) and ZP 591), and S. mikatae (IFO 1815(T)), and describe their comparison to the genomes of S. cerevisiae and S. paradoxus. The new sequences, derived by assembling millions of short DNA sequence reads together with previously published Sanger shotgun reads, have vastly greater long-range continuity and far fewer gaps than the previously available genome sequences. New gene predictions defined a set of 5261 protein-coding orthologs across the five most commonly studied Saccharomyces yeasts, enabling a re-examination of the tempo and mode of yeast gene evolution and improved inferences of species-specific gains and losses. To facilitate experimental investigations, we generated genetically marked, stable haploid strains for all three of these Saccharomyces species. These nearly complete genome sequences and the collection of genetically marked strains provide a valuable toolset for comparative studies of gene function, metabolism, and evolution, and render Saccharomyces sensu stricto the most experimentally tractable model genus. These resources are freely available and accessible through www.SaccharomycesSensuStricto.org.

Keywords: yeast species; Saccharomyces genome; evolutionary genetics; genome assembly; genomics; sensu stricto.

Figure 1

Resequencing and assembling the genomes of three Saccharomyces species. (A) Schematic showing phylogenetic relationships among nonhybrid members of the Saccharomyces sensu stricto genus plus the outgroup Kluyveromyces lactis based on (Kurtzman and Robnett 2003), (Nieduszynski and Liti 2011), and (Libkind, Hittinger et al., unpublished data). Branch lengths are not proportional to sequence divergence. The branch on which the whole-genome duplication occurred is marked. (B) Schematic depicting co-assembly of genomes from Illumina short-insert paired-end reads and mate-pair Sanger shotgun reads. Illumina reads were used to build contigs, which were stitched into scaffolds using mate-pair reads from the longer-insert Sanger libraries. Scaffolds were then joined into ultra-scaffolds (contiguous with chromosomes) using MEGABLAST and manual scaffold ordering.

Figure 2

Genes exhibiting lineage-specific rates of evolution in the Saccharomyces sensu stricto genus. (A) The three alternative hypotheses designed to test whether genes are evolving at a different rate in each of five species of the Saccharomyces sensu stricto genus. Under hypothesis H₀ all branches of the tree exhibit the same ω ratio of nonsynonymous to synonymous substitutions. Under the set of H₁ hypotheses, the ω ratio along a given species’ branch is different from that along all other branches of the tree. Under the H₂ hypothesis, each branch exhibits its own ω ratio. (B) Numbers of genes with lineage-specific rates of evolution in the Saccharomyces sensu stricto genus.

Figure 3

Relaxed molecular clock estimation of relative species divergence within the Saccharomyces sensu stricto genus. The top scale bar and the values above branches denote estimated substitutions per site. The bottom scale bar expresses species divergence in percentage points relative to the origin of the genus.