Cell size is tightly controlled in healthy tissues and single-celled organisms, but it remains unclear how cell size influences physiology. Increasing cell size was recently shown to remodel the proteomes of cultured human cells, demonstrating that large and small cells of the same type can be compositionally different. In the present study, we utilize the natural heterogeneity of hepatocyte ploidy and yeast genetics to establish that the ploidy-to-cell size ratio is a highly conserved determinant of proteome composition. In both mammalian and yeast cells, genome dilution by cell growth elicits a starvation-like phenotype, suggesting that growth in large cells is restricted by genome concentration in a manner that mimics a limiting nutrient. Moreover, genome dilution explains some proteomic changes ascribed to yeast aging. Overall, our data indicate that genome concentration drives changes in cell composition independently of external environmental cues.

在健康组织和单细胞生物中，细胞大小受到严格控制，但细胞大小如何影响生理学仍不清楚。最近显示，增加细胞大小可以重塑培养的人类细胞的蛋白质组，这表明同一类型的大细胞和小细胞在组成上可能不同。在本研究中，我们利用肝细胞倍性和酵母遗传学的自然异质性来确定倍性与细胞大小之比是蛋白质组组成的高度保守的决定因素。在哺乳动物和酵母细胞中，细胞生长引起的基因组稀释会引发类似饥饿的表型，这表明大细胞的生长受到基因组浓度的限制，以模仿限制性营养的方式。此外，基因组稀释解释了酵母老化引起的一些蛋白质组变化。总的来说，我们的数据表明，基因组浓度独立于外部环境因素驱动细胞组成的变化。