Disentangling the cost of gene expression and the emerging central dogma regulation principles

Gene expression is the most critical process in cells, producing proteins crucial for biological functions, but it also imposes a fitness cost to cell growth. While it is well known that transcription and translation can impose costs on fitness, how the costs depend on the global cell states is still unclear. Here, we model the fitness cost based on the resource competition in central dogma and successfully disentangle the fitness cost into translational cost and transcriptional cost. In particular, we show that the fitness cost depends on the copy numbers of limiting gene expression factors, such as RNA polymerase and ribosome. Our model predictions agree quantitatively with experimental data. Finally, by balancing the cost and benefit of gene expression, we show that the scaling relation between the protein copy number and the mRNA copy number can be linear or superlinear with an exponent between 1 and 2, widely observed across different organisms.