Brauer Matthew J, Huttenhower Curtis, Airoldi Edoardo M, Rosenstein Rachel, Matese John C, Gresham David, Boer Viktor M, Troyanskaya Olga G, Botstein David
Lewis-Sigler Institute for Integrative Genomics and Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Mol Biol Cell. 2008 Jan;19(1):352-67. doi: 10.1091/mbc.e07-08-0779. Epub 2007 Oct 24.
We studied the relationship between growth rate and genome-wide gene expression, cell cycle progression, and glucose metabolism in 36 steady-state continuous cultures limited by one of six different nutrients (glucose, ammonium, sulfate, phosphate, uracil, or leucine). The expression of more than one quarter of all yeast genes is linearly correlated with growth rate, independent of the limiting nutrient. The subset of negatively growth-correlated genes is most enriched for peroxisomal functions, whereas positively correlated genes mainly encode ribosomal functions. Many (not all) genes associated with stress response are strongly correlated with growth rate, as are genes that are periodically expressed under conditions of metabolic cycling. We confirmed a linear relationship between growth rate and the fraction of the cell population in the G0/G1 cell cycle phase, independent of limiting nutrient. Cultures limited by auxotrophic requirements wasted excess glucose, whereas those limited on phosphate, sulfate, or ammonia did not; this phenomenon (reminiscent of the "Warburg effect" in cancer cells) was confirmed in batch cultures. Using an aggregate of gene expression values, we predict (in both continuous and batch cultures) an "instantaneous growth rate." This concept is useful in interpreting the system-level connections among growth rate, metabolism, stress, and the cell cycle.
我们研究了在受六种不同营养物质(葡萄糖、铵、硫酸盐、磷酸盐、尿嘧啶或亮氨酸)之一限制的36种稳态连续培养物中,生长速率与全基因组基因表达、细胞周期进程和葡萄糖代谢之间的关系。超过四分之一的酵母基因表达与生长速率呈线性相关,与限制营养物质无关。负生长相关基因的子集在过氧化物酶体功能方面最为富集,而正相关基因主要编码核糖体功能。许多(并非全部)与应激反应相关的基因与生长速率密切相关,在代谢循环条件下周期性表达的基因也是如此。我们证实了生长速率与处于G0/G1细胞周期阶段的细胞群体比例之间存在线性关系,与限制营养物质无关。受营养缺陷型需求限制的培养物会浪费过量的葡萄糖,而受磷酸盐、硫酸盐或氨限制的培养物则不会;这种现象(类似于癌细胞中的“瓦伯格效应”)在分批培养中得到了证实。使用基因表达值的总和,我们预测(在连续培养和分批培养中)“瞬时生长速率”。这一概念有助于解释生长速率、代谢、应激和细胞周期之间的系统水平联系。