Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell. 2018 Apr 19;173(3):749-761.e38. doi: 10.1016/j.cell.2018.03.007. Epub 2018 Mar 29.
Coexpression of proteins in response to pathway-inducing signals is the founding paradigm of gene regulation. However, it remains unexplored whether the relative abundance of co-regulated proteins requires precise tuning. Here, we present large-scale analyses of protein stoichiometry and corresponding regulatory strategies for 21 pathways and 67-224 operons in divergent bacteria separated by 0.6-2 billion years. Using end-enriched RNA-sequencing (Rend-seq) with single-nucleotide resolution, we found that many bacterial gene clusters encoding conserved pathways have undergone massive divergence in transcript abundance and architectures via remodeling of internal promoters and terminators. Remarkably, these evolutionary changes are compensated post-transcriptionally to maintain preferred stoichiometry of protein synthesis rates. Even more strikingly, in eukaryotic budding yeast, functionally analogous proteins that arose independently from bacterial counterparts also evolved to convergent in-pathway expression. The broad requirement for exact protein stoichiometries despite regulatory divergence provides an unexpected principle for building biological pathways both in nature and for synthetic activities.
蛋白质在响应信号通路诱导时的共表达是基因调控的基本范例。然而，目前尚不清楚共调控蛋白的相对丰度是否需要精确调节。在这里，我们对 21 条不同细菌的通路和 67-224 个操纵子进行了大规模的蛋白质化学计量分析，并对相应的调控策略进行了研究。这些细菌的分离时间跨度为 0.6 亿至 20 亿年。我们使用具有单核苷酸分辨率的末端富集 RNA 测序 (Rend-seq)，发现许多编码保守通路的细菌基因簇通过内部启动子和终止子的重排，在转录物丰度和结构上发生了巨大的变化。值得注意的是，这些进化变化在转录后得到了补偿，以维持蛋白质合成速率的首选化学计量。更引人注目的是，在真核芽殖酵母中，独立于细菌对应物产生的功能类似的蛋白质也进化为在通路表达上趋同。尽管存在调控分歧，但对精确蛋白质化学计量的广泛需求为在自然和合成活动中构建生物通路提供了一个意想不到的原则。
