Singh Kapil Dev, Roschitzki Bernd, Snoek L Basten, Grossmann Jonas, Zheng Xue, Elvin Mark, Kamkina Polina, Schrimpf Sabine P, Poulin Gino B, Kammenga Jan E, Hengartner Michael O
Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Functional Genomics Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
PLoS One. 2016 Mar 17;11(3):e0149418. doi: 10.1371/journal.pone.0149418. eCollection 2016.
Complex traits, including common disease-related traits, are affected by many different genes that function in multiple pathways and networks. The apoptosis, MAPK, Notch, and Wnt signalling pathways play important roles in development and disease progression. At the moment we have a poor understanding of how allelic variation affects gene expression in these pathways at the level of translation. Here we report the effect of natural genetic variation on transcript and protein abundance involved in developmental signalling pathways in Caenorhabditis elegans. We used selected reaction monitoring to analyse proteins from the abovementioned four pathways in a set of recombinant inbred lines (RILs) generated from the wild-type strains N2 (Bristol) and CB4856 (Hawaii) to enable quantitative trait locus (QTL) mapping. About half of the cases from the 44 genes tested showed a statistically significant change in protein abundance between various strains, most of these were however very weak (below 1.3-fold change). We detected a distant QTL on the left arm of chromosome II that affected protein abundance of the phosphatidylserine receptor protein PSR-1, and two separate QTLs that influenced embryonic and ionizing radiation-induced apoptosis on chromosome IV. Our results demonstrate that natural variation in C. elegans is sufficient to cause significant changes in signalling pathways both at the gene expression (transcript and protein abundance) and phenotypic levels.
复杂性状，包括与常见疾病相关的性状，受到许多在多个途径和网络中起作用的不同基因的影响。细胞凋亡、丝裂原活化蛋白激酶（MAPK）、Notch和Wnt信号通路在发育和疾病进展中发挥重要作用。目前，我们对等位基因变异如何在翻译水平上影响这些途径中的基因表达了解甚少。在这里，我们报告了自然遗传变异对秀丽隐杆线虫发育信号通路中涉及的转录本和蛋白质丰度的影响。我们使用选择反应监测来分析从野生型菌株N2（布里斯托尔）和CB4856（夏威夷）产生的一组重组近交系（RILs）中上述四个途径的蛋白质，以进行数量性状位点（QTL）定位。在测试的44个基因中，约一半的情况显示不同菌株之间蛋白质丰度有统计学上的显著变化，然而其中大多数变化非常微弱（变化倍数低于1.3倍）。我们在染色体II的左臂上检测到一个影响磷脂酰丝氨酸受体蛋白PSR-1蛋白质丰度的远距离QTL，以及在染色体IV上影响胚胎和电离辐射诱导的细胞凋亡的两个独立QTL。我们的结果表明，秀丽隐杆线虫的自然变异足以在基因表达（转录本和蛋白质丰度）和表型水平上引起信号通路的显著变化。
