Jayapal Karthik P, Philp Robin J, Kok Yee-Jiun, Yap Miranda G S, Sherman David H, Griffin Timothy J, Hu Wei-Shou
Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota, United States of America.
PLoS One. 2008 May 7;3(5):e2097. doi: 10.1371/journal.pone.0002097.
Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels. Systems analyses of such processes incorporating large-scale transcriptome or proteome profiling can be quite revealing. Although consistency between mRNA and proteins is often implicitly assumed in many studies, examples of divergent trends are frequently observed. Here, we present a comparative transcriptome and proteome analysis of growth and stationary phase adaptation in Streptomyces coelicolor, taking the time-dynamics of process into consideration. These processes are of immense interest in microbiology as they pertain to the physiological transformations eliciting biosynthesis of many naturally occurring therapeutic agents. A shotgun proteomics approach based on mass spectrometric analysis of isobaric stable isotope labeled peptides (iTRAQ) enabled identification and rapid quantification of approximately 14% of the theoretical proteome of S. coelicolor. Independent principal component analyses of this and DNA microarray-derived transcriptome data revealed that the prominent patterns in both protein and mRNA domains are surprisingly well correlated. Despite this overall correlation, by employing a systematic concordance analysis, we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends. Integrating this data with biological information, we discovered that certain groups of functionally related genes exhibit mRNA-protein discordance in a similar fashion. Our observations suggest that differences between mRNA and protein synthesis/degradation mechanisms are prominent in microbes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level.
许多生物学过程本质上是动态的,在分子和生理水平上都会发生深刻变化。对这些过程进行系统分析,结合大规模转录组或蛋白质组分析,可能会有很大的启发。尽管在许多研究中常常隐含地假设mRNA和蛋白质之间具有一致性,但经常观察到不同趋势的例子。在这里,我们对天蓝色链霉菌生长和稳定期适应进行了比较转录组和蛋白质组分析,同时考虑了过程的时间动态。这些过程在微生物学中具有极大的研究价值,因为它们与引发许多天然治疗剂生物合成的生理转变有关。基于等压稳定同位素标记肽(iTRAQ)的质谱分析的鸟枪法蛋白质组学方法,能够鉴定并快速定量天蓝色链霉菌约14%的理论蛋白质组。对该蛋白质组数据和DNA微阵列衍生的转录组数据进行独立主成分分析发现,蛋白质和mRNA结构域中的主要模式惊人地高度相关。尽管存在这种总体相关性,但通过系统的一致性分析,我们估计超过30%的分析基因可能表现出明显不同的模式,其中近三分之一甚至呈现相反的趋势。将这些数据与生物学信息相结合,我们发现某些功能相关的基因组以类似的方式表现出mRNA-蛋白质不一致性。我们的观察结果表明,mRNA和蛋白质合成/降解机制之间的差异在微生物中很突出,同时也再次证实了这些机制在蛋白质复合物或子途径水平上协同作用的合理性。