Yale Cancer Biology Institute, West Haven, CT 06516, USA.
Yale Systems Biology Institute, West Haven, CT 06516, USA.
Sci Adv. 2022 Sep 9;8(36):eabn0756. doi: 10.1126/sciadv.abn0756.
Evolutionary profiling has been largely limited to the nucleotide level. Using consistent proteomic methods, we quantified proteomic and phosphoproteomic layers in fibroblasts from 11 common mammalian species, with transcriptomes as reference. Covariation analysis indicates that transcript and protein expression levels and variabilities across mammals remarkably follow functional role, with extracellular matrix-associated expression being the most variable, demonstrating strong transcriptome-proteome coevolution. The biological variability of gene expression is universal at both interindividual and interspecies scales but to a different extent. RNA metabolic processes particularly show higher interspecies versus interindividual variation. Our results further indicate that while the ubiquitin-proteasome system is strongly conserved in mammals, lysosome-mediated protein degradation exhibits remarkable variation between mammalian lineages. In addition, the phosphosite profiles reveal a phosphorylation coevolution network independent of protein abundance.
进化分析在很大程度上仅限于核苷酸水平。我们使用一致的蛋白质组学方法，对来自 11 种常见哺乳动物的成纤维细胞进行蛋白质组学和磷酸化蛋白质组学定量分析，以转录组作为参考。共变分析表明，哺乳动物转录本和蛋白质表达水平及其变异性与功能作用显著相关，细胞外基质相关表达的变异性最大，表明转录组-蛋白质组的协同进化很强。基因表达的生物学变异性在个体间和种间尺度上都是普遍存在的，但程度不同。RNA 代谢过程在种间的变化比个体间的变化更为显著。我们的研究结果还表明，尽管泛素-蛋白酶体系统在哺乳动物中高度保守，但溶酶体介导的蛋白质降解在哺乳动物谱系之间表现出显著的差异。此外，磷酸化位点谱揭示了一个独立于蛋白质丰度的磷酸化协同进化网络。
