A preprint defined the limits of genomic instructions: DNA provides the rules for building an organism, while physics determines the precise movements of molecules
A preprint defined the limits of genomic instructions: DNA provides the rules for building an organism, while physics determines the precise movements of molecules
In late July, bioRxiv published a preprint on the limits of genomic instructions. In the authors' model, DNA and the signals received by a cell determine which cells form a tissue and how they function. Physical processes determine the precise movements of molecules.
DNA specifies the amino acid sequences of proteins and the rules that govern how cells activate genes and respond to signals. These rules must produce a tissue in which cells and proteins perform their functions. The authors of the preprint ask whether a finite set of instructions can separately specify the exact history of every molecule.
At the tissue level, its functional state can be described by stating which cell types are present, how many proteins each cell contains, and which genes are active. An exact description of every moment would require separately specifying the position, shape, chemical modifications, and neighbors of every molecule. As the scale of description becomes finer, the organism would have to distinguish and specify an increasing number of different states with precision.
The authors illustrate this difference using a protein approximately 300 amino acids long. Its sequence carries about 1 300 bits of information, while describing the shape of its backbone to angstrom precision requires approximately 6 000 bits. Water, electric charges, and molecular collisions give this chain its specific three-dimensional shape. In the authors' model, the genome specifies the functional state, while physical processes determine its precise molecular details.
“The genome is less like a figure skating program that specifies every movement of every molecule and more like a hockey coach's plan, which sets the roster, tactics, and formation. Physics calculates the puck's exact trajectory as the game unfolds.”
In a 2018 article, geneticist Jussi Taipale formulated the same problem: the genome is finite, while cellular biochemistry contains far more measurable parameters. Some of the order within a cell arises through self-organization, as molecules bind and arrange themselves according to local physical rules. The current work calculates the level of detail at which such a description can no longer fit within the genome.
In planarians, which are flatworms, disruption of the Notum/Wnt signal that defines the head-to-tail map shifted this map in older animals, while regeneration temporarily restored fertility. In this experiment, the coordinated activity of cells in the correct location was essential.
In their discussion, the authors classify CRISPR gene editing and the control of cells with light as interventions that alter chains of cellular processes and direct the coordinated activity of cell groups. This model leads to an engineering question: which genes, chemical and electrical signals, and feedback loops can reassemble tissue with the required function?