Plant Science Center, RIKEN, Yokohama, Kanagawa, Japan.
Mol Biol Evol. 2011 Jan;28(1):377-82. doi: 10.1093/molbev/msq204. Epub 2010 Aug 24.
It is well known that knocking out a gene in an organism often causes no phenotypic effect. One possible explanation is the existence of duplicate genes; that is, the effect of knocking out a gene is compensated by a duplicate copy. Another explanation is the existence of alternative pathways. In terms of metabolic products, the relative roles of the two mechanisms have been extensively studied in yeast but not in any multi-cellular organisms. Here, to address the functional compensation of metabolic products by duplicate genes, we quantified 35 metabolic products from 1,976 genes in knockout mutants of Arabidopsis thaliana by a high-throughput Liquid chromatography-Mass spectrometer (LC-MS) analysis. We found that knocking out either a singleton gene or a duplicate gene with distant paralogs in the genome tends to induce stronger metabolic effects than knocking out a duplicate gene with a close paralog in the genome, indicating that only duplicate genes with close paralogs play a significant role in functional compensation for metabolic products in A. thaliana. To extend the analysis, we examined metabolic products with either high or low connectivity in a metabolic network. We found that the compensatory role of duplicate genes is less important when the metabolite has a high connectivity, indicating that functional compensation by alternative pathways is common in the case of high connectivity. In conclusion, recently duplicated genes play an important role in the compensation of metabolic products only when the number of alternative pathways is small.
众所周知，敲除生物体中的一个基因通常不会引起表型效应。一种可能的解释是存在重复基因；也就是说，敲除一个基因的效果可以被一个重复的副本所补偿。另一种解释是存在替代途径。就代谢产物而言，这两种机制的相对作用在酵母中得到了广泛研究，但在任何多细胞生物中都没有得到研究。在这里，为了解决代谢产物由重复基因功能补偿的问题，我们通过高通量液相色谱-质谱（LC-MS）分析定量了拟南芥敲除突变体中 1976 个基因的 35 种代谢产物。我们发现，敲除单基因或基因组中远距离同源基因的重复基因往往比敲除基因组中近同源基因的重复基因诱导更强的代谢效应，这表明只有近同源重复基因在拟南芥代谢产物的功能补偿中起着重要作用。为了扩展分析，我们检查了代谢网络中具有高或低连通性的代谢产物。我们发现，当代谢物具有高连通性时，重复基因的补偿作用就不那么重要了，这表明替代途径的功能补偿在高连通性的情况下很常见。总之，只有在替代途径数量较少的情况下，最近复制的基因才会在代谢产物的补偿中发挥重要作用。
