摘要
How cells accomplish cell size homeostasis is a fascinating topic, and several cell size regulation mechanisms were proposed: timer, sizer, and adder. Recently the adder model has received a great deal of attention. Adder property was also found in the DNA replication cycle. This paper aims to explain the adder phenomenon both in the division-centric picture and replication-centric picture at the molecular level. We established a self-replication model, and the system reached a steady state quickly based on evolution rules. We collected tens of thousands of cells in the same trajectory and calculated the Pearson correlation coefficient between biological variables to decide which regulatory mechanism was adopted by cells. Our simulation results confirmed the double-adder mechanism. Chromosome replication initiation and cell division control are independent and regulated by respective proteins.Cell size homeostasis originates from division control and has nothing to do with replication initiation control. At a slow growth rate, the deviation from adder toward sizer comes from a significant division protein degradation rate when division protein is auto-inhibited. Our results indicated the two necessary conditions in the double-adder mechanism: one is balanced biosynthesis, and the other is that there is a protein trigger threshold to inspire DNA replication initiation and cell division. Our results give insight to the regulatory mechanism of cell size and instructive to synthetic biology.
