Coordination of growth rate, cell cycle, stress response, and metabolic activity in yeast
Coordination of growth rate, cell cycle, stress response, and metabolic activity in yeast
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DOI：
10.1091/mbc.e07-08-0779
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Botstein, David
中科院分区：
文献类型：
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作者：
Brauer, Matthew J.;Huttenhower, Curtis;Botstein, David
我们研究了在六种不同营养物质(葡萄糖、铵、硫酸盐、磷酸盐、尿嘧啶或亮氨酸)限制的36种稳态连续培养中，生长速度与全基因组基因表达、细胞周期进展和葡萄糖代谢的关系。超过四分之一的酵母基因的表达与生长速度呈线性相关，与限制营养无关。负生长相关基因子集的过氧化体功能最丰富，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度密切相关，在代谢循环条件下周期性表达的基因也是如此。我们证实了生长速度与处于G0/G1细胞周期阶段的细胞所占比例呈线性关系，与营养限制无关。受营养缺乏症限制的培养物浪费过多的葡萄糖，而限制在磷酸盐、硫酸盐或氨水中的培养物则不浪费；这种现象(使人想起癌细胞中的“华宝效应”)在批次培养中得到证实。利用基因表达值的集合，我们预测(在连续培养和批量培养中)“瞬时增长率”。这一概念有助于解释生长率、新陈代谢、压力和细胞周期之间的系统水平联系。
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.