单细胞水平发现鞭毛基因表达与生长速率正相关,与群体测量结论相反
Out-of-balance growth enables cost-free synthesis of the flagellum and other proteins in a single bacterium
研究在单细胞水平发现,大肠杆菌(Escherichia coli)鞭毛基因活性与生长速率升高相关,这与群体测量中鞭毛基因表达伴随生长减慢的经典结论相反。作者认为这一矛盾类似辛普森悖论,源于群体测量把单细胞数据不加区分地汇总,而逐细胞同时考察瞬时生长与基因表达时关系方向发生反转。作者将这一现象归因于失衡生长带来的短暂加速,暂时抵消了鞭毛合成的负担,可能来自细胞分裂时继承的生长因子盈余。在组成型启动子驱动荧光蛋白表达的合成系统中也观察到类似效应,说明该关系具有普遍性。计算模型显示,亲代生长因子的继承可以解释这一表观矛盾,并构成单细胞中缓解非必需且高耗能基因短期成本的一般机制。
来源:eLife · doi.org
The cost of expressing unnecessary genes on growth has been explained at the population level through balanced growth assumptions. However, due to the high degree of stochasticity in growth and gene regulation, it remains unclear how classical growth laws derived from bulk measurements manifest at the level of individual cells. For example, flagellar gene expression, one of the most energy-intensive processes in Escherichia coli , is typically associated with reduced growth rates in bulk measurements. By contrast, we find at the single-cell level that a strikingly opposite behavior coexists: flagellar gene activity is associated with an increase in growth rate. We show that this apparent contradiction, reminiscent of Simpson’s paradox, results from examining in each cell instantaneous growth and gene expression without indiscriminately aggregating the single-cell data like in bulk measurements. We attribute this unrecognized behavior to out-of-balance growth boosts that temporarily offset the burden of flagellum production, likely driven by a surplus of growth factors inherited across cell division. Furthermore, we show that this non-intuitive relationship between growth and gene expression at the single-cell level is general, as we observe similar effects with synthetic systems driving the expression of fluorescent proteins downstream of constitutive promoters. Finally, we use a computational model to show that the inheritance of parental growth factors can explain the apparent contradiction and constitutes a general mechanism for mitigating the short-term cost of nonessential and biosynthetically demanding genes in the single cell.