Organisms

Saccharomyces cerevisiae is arguably the most important model organism for studies of genetics and eukaryotic biology. As the first eukaryote to have its genome sequenced, it has also become the model of choice for functional and comparative genomics. To date, the sequence of only a single laboratory strain of S. cerevisiae, S288C, is available. The sequence of an independent natural isolate will greatly enhance biological, genomic, and evolutionary studies. High-quality draft sequence of three related Saccharomyces species was recently generated (Kellis et al. 2003). The sequence divergence between S. paradoxus (the closest of these species) and S. cerevisiae is 20%, considerably greater than that between human and rhesus macaque. In contrast, the sequence divergence between RM11 and S288C is estimated to be 0.5-1%, approaching that between human and chimp. This sequence variation is distributed throughout the genome, confirming that RM11 shares no recent history with S288C.

The sequence of a natural isolate will allow identification of mutations specific to S288C on a genome-wide basis and enable studies of the true wild-type alleles, as well as shedding light on natural genetic variation within S. cerevisiae. The sequence of RM11 will also identify S. cerevisiae genes deleted in S288C and quantify the rate of intraspecific telomeric "genome churning." RM11 has been used as a model for mapping loci that affect gene expression and other complex phenotypes, and the sequence will greatly facilitate positional cloning of the genes involved.

RM11-1a is a haploid derivative of Bb32(3), a natural isolate collected by Robert Mortimer from a California vineyard. It has high spore viability (80-90%) when crossed with different lab strains. Strains of both mating types and with a number of auxotrophic markers are available. RM11 has been subject of extensive phenotypic characterization, including growth under a wide range of conditions and gene expression profiling. Measurements of gene expression in RM11, S288C, and segregants from a cross between them show that 1/3-1/2 of the genome is differentially expressed, and that these differences are due to at least 500-1000 separate loci, some of which affect expression in cis and others in trans. Sequence of RM11 will greatly facilitate rapid identification of these loci and comprehensive characterization of regulatory variation. RM11 also has significantly longer life span than laboratory yeast strains and accumulates age-associated abnormalities at a lower rate.