De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology

The 1000-dollar genome, an iconic goal in human genomics, is already a reality for the yeast Saccharomyces cerevisiae (based on September 2011 quotes from several sequencing companies for sequencing a 12 Mb genome via paired-end short-read sequencing, at over 40-fold coverage).Although a high quality reference genome of the laboratory strain S. cerevisiae S288C has been available since 1996 [1], there are four main reasons to (re)sequence the genomes of other S. cerevisiae strains. First, the considerable sequence divergence among S. cerevisiae species may cause practical complications, for example, the design of oligonucleotide arrays and cassettes for gene disruption in non-S288C strains. The discovery of > 250,000 polymorphisms in 71 S. cerevisiae strains sequenced at low coverage [2] illustrates that this is not a trivial problem. Secondly, although the genomes of S. cerevisiae strains appears to be much more strongly conserved than those of other organisms, such as E. coli [3], S. cerevisiae strains do show physiologically relevant differences in their gene complement. For example, the absence of a functional MALx3 gene in S. cerevisiae S288C leads to a maltose-negative phenotype, while an atypical ENA gene complement renders the laboratory strain CEN.PK113-7D more sensitive to lithium ions [4]. The possible importance of strain-specific genes is illustrated by the identification of a probable horizontal gene transfer event in the S. cerevisiae wine strain EC1118, that led to the acquisition of genes from the spoilage yeast Zygosaccharomyces bailii [5]. Third, in addition to the presence or absence of coding regions, differences can occur in non-coding regions, such as promoter regions. Knowledge of such differences is essential for the analysis and modelling of regulatory networks in systems biology [6]. Finally, laboratory evolution is rapidly gaining popularity as a tool to analyse genome function and to select for yeast strains with industrially relevant pr