Daniel Jacques H
Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, rue de la Terrasse, 91198, Gif-sur-Yvette, France.
Mol Genet Genomics. 2009 Apr;281(4):437-45. doi: 10.1007/s00438-008-0416-4. Epub 2009 Jan 17.
Genetics, genomics, and biochemistry have all been of immense help in characterizing macromolecular cell entities and their interactions. Still, obtaining an overall picture of the functioning of even a simple unicellular species has remained a challenging task. One possible way to obtain a comprehensive picture has been described: by capitalizing on the observation that the overexpression on a multicopy plasmid of apparently any wild-type gene in yeast can lead to some negative effect on cell fitness (referring to the concept of "gene toxicity"), the FIG (fitness-based interferential genetics) approach was devised for selecting normal genes that are in antagonistic (and potentially also agonistic) relationship with a particular gene used as a reference. Herein, we take a complementary approach to FIG, by first selecting a "hypertoxic" allele of the reference gene--which easily provides the general possibility of obtaining gene products with the remarkable property of being inactive without altering their macromolecular interactivity--and then looking for the genes that interact functionally with this reference. Thus, FIG and the present approach (Trap-FIG), both taking advantage of the negative effects on cell fitness induced by various quantitative modulations in cellular networks, could potentially pave the way for the emergence of efficient in situ biochemistry.
遗传学、基因组学和生物化学在表征大分子细胞实体及其相互作用方面都提供了巨大帮助。然而，即便要全面了解一个简单单细胞物种的功能，仍然是一项具有挑战性的任务。一种获取全面图景的可能方法已被描述：利用这样的观察结果，即酵母中任何野生型基因在多拷贝质粒上的过表达都可能对细胞适应性产生一些负面影响（指“基因毒性”概念），于是设计了基于适应性的干扰遗传学（FIG）方法，用于筛选与用作参考的特定基因存在拮抗（也可能是激动）关系的正常基因。在此，我们采用一种与FIG互补的方法，首先选择参考基因的“高毒性”等位基因——这很容易提供获得具有显著无活性特性且不改变其大分子相互作用性的基因产物的一般可能性——然后寻找与该参考基因发生功能相互作用的基因。因此，FIG和本方法（Trap - FIG），二者都利用细胞网络中各种定量调节对细胞适应性产生的负面影响，有可能为高效原位生物化学的出现铺平道路。
