Interdependence of Cell Growth and Gene Expression: Origins and Consequences

Theory of Growth Control

Although quantitative studies of growth in bacterial cultures have been made for over 50 years, the relationship between cell proliferation and gene expression has not been clear. Scott et al. (p. [Related article:]1099 ; see the Perspective by [Related article:] Lerman and Palsson ) have revealed that mass per cell exponentially increased with linear increases in growth rate and that ribosome abundance increased linearly with growth rate depending on the rate of translation. Hence, the systems properties of the biological processes involved in growth can be derived without any molecular understanding of their basis and can be used to establish fundamental properties for the design of biotechnological procedures.

Abstract

Simple mathematical models describe the relationship between bacterial replication, cellular resources, and protein expression.

Abstract

In bacteria, the rate of cell proliferation and the level of gene expression are intimately intertwined. Elucidating these relations is important both for understanding the physiological functions of endogenous genetic circuits and for designing robust synthetic systems. We describe a phenomenological study that reveals intrinsic constraints governing the allocation of resources toward protein synthesis and other aspects of cell growth. A theory incorporating these constraints can accurately predict how cell proliferation and gene expression affect one another, quantitatively accounting for the effect of translation-inhibiting antibiotics on gene expression and the effect of gratuitous protein expression on cell growth. The use of such empirical relations, analogous to phenomenological laws, may facilitate our understanding and manipulation of complex biological systems before underlying regulatory circuits are elucidated.