Perlstein Ethan O, Ruderfer Douglas M, Ramachandran Gopal, Haggarty Stephen J, Kruglyak Leonid, Schreiber Stuart L
Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
Chem Biol. 2006 Mar;13(3):319-27. doi: 10.1016/j.chembiol.2006.01.010.
Here 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.
在此，我们证明酿酒酵母的自然变体是用于系统研究复杂性状，特别是对小分子反应的模型系统。作为广泛用于研究单个基因功能的酿酒酵母人工敲除文库的补充，我们使用通过减数分裂重组产生的314个和1932个成员的突变菌株文库，来研究自然突变对23种小分子干扰剂（SMP）诱导的表型的累积、定量影响。这种方法揭示了SMP之间的合成致死性，并且遗传图谱研究证实多个数量性状基因座参与了对影响呼吸过程的两种SMP的反应。酵母自然变体与调节进化保守细胞过程的小分子的系统组合能够更好地理解复杂性状的一般特征。
