Revealing complex traits with small molecules and naturally recombinant yeast strains
Revealing complex traits with small molecules and naturally recombinant yeast strains
复制标题
DOI：
10.1016/j.chembiol.2006.01.010
复制
发表时间：
2006-03-01
影响因子：
--
通讯作者：
Schreiber, SL
中科院分区：
文献类型：
--
作者：
Perlstein, EO;Ruderfer, DM;Schreiber, SL
在这里，我们证明了酵母的自然变异是系统研究复杂性状的模型系统，特别是对小分子的反应。作为广泛用于研究单个基因功能的酿酒酵母人工敲除集合的补充，我们利用减数分裂重组产生的突变菌株的314和1932个成员文库，研究了23种小分子扰动原（SMPs）诱导的自然突变对表型的累积定量影响。这种方法揭示了SMPs之间的合成致死率，遗传作图研究证实了多个数量性状位点参与了对两种影响呼吸过程的SMPs的反应。酵母的自然变异和调节进化保守的细胞过程的小分子的系统结合可以更好地理解复杂性状的一般特征。
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.