(P1) Technology Development in a Multidisciplinary Center.

Variation in RNA, protein, and metabolite levels among individuals is an important source of physiological and phenotypic differences within and between species. However, relatively little is known about the magnitude and genetic basis of these high-dimensional molecular phenotypes. Yeast provide an ideal model system for the genetic dissection of complex and quantitative traits, and whole-genome sequences are accumulating for dozens of Saccharomyces cerevisiae strains isolated from natural, industrial, and lab environments. We grew a diverse selection of sequenced strains in continuous culture and used a randomized and replicated study design. We exploited all the technologies in the Yeast Resource Center to obtain high quality and high coverage measurements of RNA, protein, metabolite, and morphological phenotypes. The resulting data sets provide a unique and powerful opportunity to combine comparative functional genomics data with comparative sequence analyses and delineate the genetic architecture of complex and quantitative phenotypes in yeast. Our initial analyses indicate that a high degree of strain-to-strain variation exists at all systems levels, and that this variation largely correlates with strain relatedness as measured by sequence comparison. Variation in RNA levels correlates with the corresponding peptides and related metabolites in complex ways. These experiments have resulted in an important large-scale data set of thousands of quantitative traits collected in a carefully designed randomized study, which will provide novel insights into the magnitude and patterns of natural variation of molecular and morphological phenotypes, as well as preliminary insights into their genetic basis.