SRA

Lager brewing strains of Saccharomyces pastorianus are natural interspecific hybrids originating from spontaneous hybridization of Saccharomyces cerevisiae and Saccharomyces eubayanus. Over the past 500 years, S. pastorianus has been domesticated to become one of the most important industrial microorganisms. Production of lager-type beers requires a set of essential phenotypes, including the ability to ferment maltose and maltotriose at low temperature, production of flavors and aromas and the ability to flocculate. Understanding the molecular basis of complex brewing-related phenotypic traits is a prerequisite for rational strain improvement. While genome sequences have been reported, the variability and dynamics of S. pastorianus genomes has not been investigated in detail. Here, using deep sequencing and chromosome copy number analysis, we show that S. pastorianus strain CBS1483 exhibits extensive aneuploidy. This was confirmed by quantitative PCR and by flow cytometry. As a direct consequence of this aneuploidy, a massive number of sequence variants was identified, leading to at least 1800 additional protein variants in S. pastorianus CBS1483. Analysis of eight additional S. pastorianus strains revealed that the previously defined 'Group I' strains showed comparable karyotypes, while 'Group II' strains showed large inter-strain karyotypic variability. Comparison of three strains with near-identical genome sequences revealed substantial chromosome copy number variation, which may contribute to strain-specific phenotypic traits. The observed variability of lager yeast genomes demonstrates that systematic linking of genotype to phenotype requires a three-dimensional genome analysis, encompassing physical chromosomal structures, copy number of individual chromosomes or chromosomal regions, and allelic variation of copies of individual genes