Aneuploidy and copy number breakpoints in the genome of lager yeasts mapped by microarray hybridisation.

Competitive comparative genome hybridisation (CCGH) to Saccharomyces cerevisiae DNA microarrays and quantitative real-time polymerase chain reaction (qRT-PCR) assays are used to examine the copy number of S. cerevisiae-like genes, at single gene resolution, of two bottom-fermenting lager yeast strains, CMBS-33 and 6701. Using the S. cerevisiae gene order for each chromosome, we observe that the copy number for contiguous groups of S. cerevisiae-like genes is similar in both strains. However, discrete changes in copy number occur at distinct loci, indicating the aneuploid nature of the lager yeast genomes. The majority of loci where copy number changes occur are conserved in both strains. We also identify a large segment of S. cerevisiae DNA on chromosome XVI that fails to hybridise to genomic DNA from both lager strains, suggesting that this region may have diverged significantly or is absent in the lager yeast strains. Furthermore, very low levels of mRNA transcripts are detected from this region of the genome. Interestingly, the increased gene copy number observed elsewhere (e.g. chromosome III) does not correlate specifically with increased gene expression under fermentation conditions, suggesting that dosage compensation may play a role in controlling gene expression in these strains.