Scientific Publications

Revealing complex traits with small molecules and naturally recombinant yeast strains.

Publication TypeJournal Article
AuthorsPerlstein, EO, Ruderfer DM, Ramachandran G., Haggarty SJ, Kruglyak L., and Schreiber SL
AbstractHere we demonstrate that natural variants of the yeast Saccharomyces cerevisiae are a model system for the systematic study of complex traits, specifically the response to small molecules. As a complement to artificial knockout collections of S. cerevisiae widely used to study individual gene function, we used 314- and 1932-member libraries of mutant strains generated by meiotic recombination to study the cumulative, quantitative effects of natural mutations on phenotypes induced by 23 small-molecule perturbagens (SMPs). This approach reveals synthetic lethality between SMPs, and genetic mapping studies confirm the involvement of multiple quantitative trait loci in the response to two SMPs that affect respiratory processes. The systematic combination of natural variants of yeast and small molecules that modulate evolutionarily conserved cellular processes can enable a better understanding of the general features of complex traits.
Year of Publication2006
JournalChemistry & biology
Date Published (YYYY/MM/DD)2006/03/01
ISSN Number1074-5521