Kamkina Polina, Snoek L Basten, Grossmann Jonas, Volkers Rita J M, Sterken Mark G, Daube Michael, Roschitzki Bernd, Fortes Claudia, Schlapbach Ralph, Roth Alexander, von Mering Christian, Hengartner Michael O, Schrimpf Sabine P, Kammenga Jan E
From the ‡Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland; §Ph.D. Program in Molecular Life Sciences Zurich, 8057 Zurich, Switzerland;
‖Laboratory of Nematology, Wageningen University, Wageningen 6708 PB, The Netherlands;
Mol Cell Proteomics. 2016 May;15(5):1670-80. doi: 10.1074/mcp.M115.052548. Epub 2016 Mar 4.
Natural genetic variation is the raw material of evolution and influences disease development and progression. An important question is how this genetic variation translates into variation in protein abundance. To analyze the effects of the genetic background on gene and protein expression in the nematode Caenorhabditis elegans, we quantitatively compared the two genetically highly divergent wild-type strains N2 and CB4856. Gene expression was analyzed by microarray assays, and proteins were quantified using stable isotope labeling by amino acids in cell culture. Among all transcribed genes, we found 1,532 genes to be differentially transcribed between the two wild types. Of the total 3,238 quantified proteins, 129 proteins were significantly differentially expressed between N2 and CB4856. The differentially expressed proteins were enriched for genes that function in insulin-signaling and stress-response pathways, underlining strong divergence of these pathways in nematodes. The protein abundance of the two wild-type strains correlates more strongly than protein abundance versus transcript abundance within each wild type. Our findings indicate that in C. elegans only a fraction of the changes in protein abundance can be explained by the changes in mRNA abundance. These findings corroborate with the observations made across species.
自然遗传变异是进化的原材料，并影响疾病的发生和发展。一个重要的问题是这种遗传变异如何转化为蛋白质丰度的变异。为了分析遗传背景对线虫秀丽隐杆线虫基因和蛋白质表达的影响，我们定量比较了两个遗传差异很大的野生型菌株N2和CB4856。通过微阵列分析来分析基因表达，并使用细胞培养中氨基酸的稳定同位素标记对蛋白质进行定量。在所有转录基因中，我们发现有1532个基因在两种野生型之间存在差异转录。在总共3238种定量蛋白质中，有129种蛋白质在N2和CB4856之间存在显著差异表达。差异表达的蛋白质在胰岛素信号传导和应激反应途径中发挥作用的基因中富集，这突出了线虫中这些途径的强烈差异。两种野生型菌株的蛋白质丰度之间的相关性比每种野生型内蛋白质丰度与转录本丰度之间的相关性更强。我们的研究结果表明，在秀丽隐杆线虫中，只有一部分蛋白质丰度的变化可以由mRNA丰度的变化来解释。这些发现与跨物种的观察结果一致。
