Defining genetic interaction
Defining genetic interaction
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DOI：
10.1073/pnas.0712255105
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发表时间：
2008-03-04
影响因子：
11.1
通讯作者：
Roth, Frederick P.
中科院分区：
文献类型：
--
作者：
Mani, Ramamurthy;Onge, Robert P. St.;Roth, Frederick P.
有时两个基因的突变会产生一种表型，这种表型在每个突变的个体影响下都是令人惊讶的。这种现象定义了基因相互作用，可以揭示基因和途径之间的功能关系。例如，具有惊人缓慢生长的双突变体定义了协同相互作用，可以识别补偿途径或蛋白质复合物。最近的研究使用了四种数学上不同的遗传相互作用定义（这里称为Product， Additive， Log和Min）。这种选择是否具有实际后果尚不清楚，因为在某些条件下，这些定义产生相同的结果。在这里，我们展示了在不同定义之间的选择可以产生深远的影响。虽然已知的酵母中52%的协同遗传相互作用是根据Min定义推断出来的，但我们发现Product和Log定义（这里显示的实际上是等效的）在识别功能关系方面都比Min更好。此外，我们表明，在群体遗传学中常用的添加剂和对数定义导致了与有性生殖的选择优势相关的不同结论。
Sometimes mutations in two genes produce a phenotype that is surprising in light of each mutation's individual effects. This phenomenon, which defines genetic interaction, can reveal functional relationships between genes and pathways. For example, double mutants with surprisingly slow growth define synergistic interactions that can identify compensatory pathways or protein complexes. Recent studies have used four mathematically distinct definitions of genetic interaction (here termed Product, Additive, Log, and Min). Whether this choice holds practical consequences has not been clear, because the definitions yield identical results under some conditions. Here, we show that the choice among alternative definitions can have profound consequences. Although 52% of known synergistic genetic interactions in Saccharomyces cerevisiae were inferred according to the Min definition, we find that both Product and Log definitions (shown here to be practically equivalent) are better than Min for identifying functional relationships. Additionally, we show that the Additive and Log definitions, each commonly used in population genetics, lead to differing conclusions related to the selective advantages of sexual reproduction.