Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
Mol Cell. 2012 Jun 8;46(5):691-704. doi: 10.1016/j.molcel.2012.05.028.
To date, cross-species comparisons of genetic interactomes have been restricted to small or functionally related gene sets, limiting our ability to infer evolutionary trends. To facilitate a more comprehensive analysis, we constructed a genome-scale epistasis map (E-MAP) for the fission yeast Schizosaccharomyces pombe, providing phenotypic signatures for ~60% of the nonessential genome. Using these signatures, we generated a catalog of 297 functional modules, and we assigned function to 144 previously uncharacterized genes, including mRNA splicing and DNA damage checkpoint factors. Comparison with an integrated genetic interactome from the budding yeast Saccharomyces cerevisiae revealed a hierarchical model for the evolution of genetic interactions, with conservation highest within protein complexes, lower within biological processes, and lowest between distinct biological processes. Despite the large evolutionary distance and extensive rewiring of individual interactions, both networks retain conserved features and display similar levels of functional crosstalk between biological processes, suggesting general design principles of genetic interactomes.
迄今为止，种间遗传互作组的比较仅限于小的或功能相关的基因集，限制了我们推断进化趋势的能力。为了促进更全面的分析，我们构建了裂殖酵母 Schizosaccharomyces pombe 的全基因组上位性图谱 (E-MAP)，为非必需基因组的~60%提供了表型特征。利用这些特征，我们生成了 297 个功能模块的目录，并为 144 个以前未被描述的基因赋予了功能，包括 mRNA 剪接和 DNA 损伤检查点因子。与芽殖酵母酿酒酵母的综合遗传互作组进行比较，揭示了遗传互作进化的层次模型，在蛋白质复合物内的保守性最高，在生物过程内的保守性较低，而在不同的生物过程之间的保守性最低。尽管进化距离很大，并且单个相互作用的重新布线很多，但两个网络都保留了保守的特征，并在生物过程之间显示出类似水平的功能串扰，这表明遗传互作组具有一般的设计原则。
