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The ability to replicate is a key feature of the living world. Organisms can replicate themselves and their cells, while DNA, RNA, and proteins are made through processes that copy molecular templates. Copying DNA requires energy, pushing the system out of balance and causing energy loss.

Researchers from the Max Planck Institute for the Physics of Complex Systems (MPIPKS) and the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) have provided new insights into the physical conditions that need to be achieved for enabling an accurate copying process. “Our theory considers both the energy-driven process of making template-based copies and the natural, spontaneous assembly of molecules, as well as the reverse of these processes,” explains Arthur Genthon, the first author of the study pursued together with Frank Jülicher (both MPIPKS), as well as Carl Modes and Stephan Grill (both MPI-CBG). To focus on the core principles of copying, the researchers used a minimal approach based on one-step processes that averages over complex molecular details.

In the minimal setup the researchers considered, they could identify a clear boundary between accurate and inaccurate copy processes. They found that crossing this boundary to achieve accurate copying requires the energy that is spent in the process to surpass a particular threshold. They have thus determined the thermodynamic cost required to achieve precision in replication. The work reveals a cost-accuracy trade-off: using more types of building blocks (monomers) uses less energy but makes copying less accurate. Though inspired by DNA, this framework can apply to any information transfer system, like RNA-to-protein translation.